Safe Prescription Recommendations for Non Steroidal Anti-inflammatory Drugs: Consensus Document Elaborated by Nominated Experts of Three Scientific Associations (SER-SEC-AEG)

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Gonzalez-Juanatey" "autores" => array:10 [ 0 => array:4 [ "nombre" => "Angel" "apellidos" => "Lanas" "email" => array:1 [ 0 => "alanas@unizar.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "¿" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Pere" "apellidos" => "Benito" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Joaquín" "apellidos" => "Alonso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Blanca" "apellidos" => "Hernández-Cruz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "Gonzalo" "apellidos" => "Barón-Esquivias" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "#" "identificador" => "fn1" ] ] ] 5 => array:3 [ "nombre" => "Ángeles" "apellidos" => "Perez-Aísa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 6 => array:3 [ "nombre" => "Xavier" "apellidos" => "Calvet" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "g" "identificador" => "aff0035" ] ] ] 7 => array:3 [ "nombre" => "José Francisco" "apellidos" => "García-Llorente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "h" "identificador" => "aff0040" ] ] ] 8 => array:3 [ "nombre" => "Milena" "apellidos" => "Gobbo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "i" "identificador" => "aff0045" ] ] ] 9 => array:3 [ "nombre" => "José R." "apellidos" => "Gonzalez-Juanatey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "j" "identificador" => "aff0050" ] ] ] ] "afiliaciones" => array:10 [ 0 => array:3 [ "entidad" => "Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa, Universidad de Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "i+D+I, Unidad de Gestión Clínica de Reumatología, Servicio de Reumatología, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Cardiología, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Unidad de Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servei de Digestiu, Hospital de Sabadell, Universidad Autónoma de Barcelona, CIBERehd, Sabadell, Barcelona, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Unidad de Reumatología, Hospital de Tortosa, Tortosa, Tarragona, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario, Santiago de Compostela, La Coruña, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG)" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2888 "Ancho" => 3277 "Tamanyo" => 268940 ] ] "descripcion" => array:1 [ "en" => "Algorithm recommendations for the use of NSAIDs according to the cardiovascular and gastrointestinal risk (upper and lower digestive tract). * If necessary naproxen+PPI or celecoxib at low doses (200mg/24h)±PPI as soon as possible in both cases. ** More robust information for celecoxib than for etoricoxib # Naproxen should be taken 2h before ASA. Ifenteric coated aspirin are used, interaction possibilities are greater. ## If there is a prior cardiovascular event, EMA and AEM currently contraindicate this option. It is assumed that patients with very high cardiovascular risk should be treated with ASA. Therefore, in the group of low gastrointestinal risk, very high cardiovascular risk is not contemplated, because use of ASA, and gastrointestinal risk is intermediate at best." ] ] ] "textoCompleto" => "IntroductionNonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with a heterogeneous chemical structure that share antipyretic, anti-inflammatory and analgesic activity through their ability to inhibit cyclooxygenase (COX), involved in the synthesis of prostaglandins, thromboxanes and leukotrienes. They are the cornerstone in the treatment of pain and inflammation in patients with musculoskeletal diseases.Prostaglandins are produced from an arachidonic acid oxidative pathway and COX enzymes. There are three forms of COX (COX-1, COX-2, and COX-3), with the first two being the most significant. COX-3 is an isoform of COX-1, which only differs in the structure of an amino acid, and its function, but is believed to be antipyretic, although this remains uncertain. In a simple way, it can be said that COX-1 acts at the onset of platelet aggregation and at the defense mechanisms level of the gastrointestinal (GI) mucosa, while COX-2 appears to be involved in pain mediation, fever and inflammation. Inhibition of COX enzymes is related to beneficial and unwanted effects on major organ systems where COX activity plays a key role.The introduction of drugs that function as selective inhibitors of COX-2 induced high expectations when it was proven that they presented an efficacy equal to that of nonselective NSAIDs but with a safer GI toxicity profile. Subsequently, the observation of an increased frequency of cardiovascular (CV) events cooled these expectations but opened a very important way to understand not only the benefits but also all the side effects associated with the use of NSAIDs. In October 2006, the Committee for Medicinal Products for Human Use of the EMEA issued a report<a class="elsevierStyleCrossRef" href="#bib0005">1</a> regarding the existence of new data on the risks of atherothrombotic CV type events related to traditional NSAIDs. So it is currently considered that all NSAIDs, in varying degrees, are associated with increased GI and CV risk. The increased CV risk due to the use of selective COX-2 is explained by an imbalance between inhibition of thromboxane and prostacyclin, but given that the increased CV risk is also seen with nonselective classic NSAIDs, the mechanism appears to be more complex. Moreover, both traditional and COX-2 NSAIDs are associated with an increase in blood pressure and edema, to varying degrees.In 2003, the Spanish Gastroenterological Association (ALA) and the Spanish Society of Rheumatology (SER) contributed to the publication of a “clinical strategy for the prevention of adverse effects on the digestive tract by NSAIDs”,<a class="elsevierStyleCrossRefs" href="#bib0010">2,3</a> and then, a consensus document of the SER and the Mexican College of Rheumatology for the “Appropriate use of NSAIDs in rheumatology”<a class="elsevierStyleCrossRef" href="#bib0020">4</a> was published in the year 2009. The current review is a collaboration of ALA, the SER and the Spanish Society of Cardiology (SEC). This review aims to promote a rational use of NSAIDs according to new studies published in recent years and help in an optimal decision-making process for the routine use of these drugs.Operational Definitions of the DocumentThe term NSAID in these recommendations refers to traditional NSAIDs as a group, to selective COX-2 (coxibs) inhibitors and acetylsalicylic acid (ASA) at anti-inflammatory doses. If a statement refers only to traditional NSAIDs, coxibs or ASA, this will be well specified in the recommendation. We have not included other NSAID analgesics, such as lysine clonixinate or metamizole.MethodologyThe development of consensus was performed using a nominal group and the Delphi technique as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Nominal GroupNine panelists (three rheumatologists, 3 gastroenterologists and 3 cardiologists) from their respective scientific societies (SER, ALA and SEC) and appointed by the boards of the same based on their experience and/or publications on the topic in journals included in Medline, formed the nominal group. This group was coordinated by a methodologist of the Research Unit of the SER that established the scope, users, and paragraphs of consensus, and the definitions used in the document.To carry out the group, the panelists were provided with documents published previously on the subject, and asked everyone to, with no interaction among them, develop their personal proposal following a scheme provided by the methodologist of the Research Unit of the SER, who subsequently developed a joint document that included all proposals. On 15 June 2012 the actual meeting where the background of the problem and the relevant methodological aspects were revised consensus took place. Then, the group worked on the entire document and tested each of the aspects to agree on (user, scope and topics to be included). Each expert participant had the opportunity to vote on the appropriateness or otherwise of the inclusion of each of the proposed recommendations, arguing the reasons for it. Thus, the options, the final structure of the document and the heads of the sections hereof, were successively rearranged. Finally it was decided that the consensus would address primary care physicians, rheumatologists, cardiologists and gastroenterologists (as users), and would focus on issues of efficacy, CV security and kidney safety (range). Those responsible for each of the paragraphs were distributed as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Drafting of RecommendationsThe recommendations were drafted by experts, either individually or in working groups. A common approach was established for its development, so that each responsible manager should include a short, synthetic statement of recommendation, followed by its argumentative development, supporting the recommendation with the best available evidence-based literature searches made for such a purpose by each panelist. The level of evidence and strength of recommendation were established according to the SIGN<a class="elsevierStyleCrossRef" href="#bib0025">5</a> scale.Delphi SurveyTo establish the degree of consensus, a 2 round Delphi survey was conducted. The recommendations submitted by the panelists were reformulated in the form of items to be answered using a Likert scale that measured the degree of agreement with the statement, scoring it as 1 (completely disagree) to 5 (completely agree). Questionnaires were sent electronically via email to the panelists insuring that there was no interaction between them.The first round was sent on January 28, 2013 (66 items grouped in 17 sections). In the first round, panelists were able to add new claims, comments, quotes or arguments for each item when, from their point of view, they were important aspects that should be included in the consensus document.It was felt that there was agreement with the item when the average score was equal to or greater than 4, and disagreement when the score was less than or equal to 2. In both cases (agreement and disagreement) there is consensus. In the rest of the possibilities, it was considered that the item was problematic and no consensus could be established. Based on the comments of the panelists the wording of some items was modified, others were broken up and a list of possible new recommendations to be included in the questionnaire for the second round was added.The second round was sent on February 11, 2013 (73 items grouped in 17 sections). Analysis of the second round was performed using the same methodology and the same criteria were used as in the first (agreement or disagreement and conflicting items). It was felt that there was a consensus when more than 75% of the panelists agreed with the statement (agreement score ≥4). The remaining cases (conflicting items) are considered recommendations without consensus, and are not included herein.RecommendationsEfficacyDirections<elsevierMultimedia ident="tb0005"></elsevierMultimedia>The approved indications for NSAID on the insert are varied, according to the type of pain ranging from those originated in the musculoskeletal or neurological system to dysmenorrhea. This makes the target population very broad and heterogeneous. NSAID responses vary among individuals, which obliges the individualization of the indication and evaluation of such a response to these drugs.<a class="elsevierStyleCrossRef" href="#bib0020">4</a><elsevierMultimedia ident="tb0010"></elsevierMultimedia>One cannot recommend any NSAID over another based on their clinical response. Several publications provide sufficient evidence to assert that efficacy is similar.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a>Time of Use<elsevierMultimedia ident="tb0015"></elsevierMultimedia>To control pain, NSAIDs share indications with other pharmacological and non-pharmacological interventions. NSAIDs should be used for the shortest duration and the lowest possible dose, adapting their use to different approved indications. This recommendation is collected by regulatory agencies,<a class="elsevierStyleCrossRefs" href="#bib0005">1,8</a> based on data showing dose-dependent adverse effects and that the risk is maintained over time. Therefore, given the potential for adverse effects, its use is recommended when the alternatives are not possible, both for intolerance as for ineffectiveness.<a class="elsevierStyleCrossRefs" href="#bib0045">9–11</a>In osteoarthritis, NSAIDs continuous treatment is most effective in controlling the symptoms than on-demand use. Nevertheless, the latter is often recommended because of possible undesirable side effects, as stated in a study lasting 22 weeks for the prevention of outbreaks of osteoarthritis of the knee and hip.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> In another prospective multicenter randomized trial of 24 weeks in patients with hip or knee osteoarthritis, the frequency of adverse effects was similar in those taking celecoxib continuously compared to those taking it intermittently depending on the symptoms of<a class="elsevierStyleCrossRef" href="#bib0065">13</a> the patients. In psoriatic arthritis, due to the intestinal and CV specific risks of these patients, NSAIDs are recommended at the lowest dose and for the shortest time possible due to their potential toxicity.<a class="elsevierStyleCrossRef" href="#bib0070">14</a><elsevierMultimedia ident="tb0020"></elsevierMultimedia>In ankylosing spondylitis NSAIDs are recommended as first-line therapy if patients present with inflammatory back pain and stiffness, being continued as treatment of choice if the disease is active and persistently symptomatic.<a class="elsevierStyleCrossRefs" href="#bib0075">15–18</a> NSAIDs improve function and decrease disease activity in ankylosing spondylitis, while disease-modifying drugs have no effect on these parameters.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> There has also been a reduction in the degree of radiographic progression in patients who take NSAIDs continuously associated with anti-TNF drugs.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> Similarly, continued treatment with celecoxib is associated with a lower radiographic progression compared with on demand use.<a class="elsevierStyleCrossRef" href="#bib0105">21</a> The German Early Spondyloarthritis Inception Cohort notes that patients with ankylosing spondylitis associated with a high rate of NSAID use for more than 2 years have a slowing of new spinal bone formation compared to the those that have a low rate. This apparent protective effect is exclusive of those patients with high C-reactive protein in time and the presence of syndesmophytes at onset.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> Patients with elevated acute phase reactants benefit more from continuous treatment with NSAIDs.<a class="elsevierStyleCrossRefs" href="#bib0115">23–25</a>Quality of Life<elsevierMultimedia ident="tb0025"></elsevierMultimedia>The efficacy of NSAIDs in reducing pain and symptoms associated with inflammation in patients with acute or chronic rheumatic disease is unquestionable.<a class="elsevierStyleCrossRefs" href="#bib0130">26,27</a> These benefits produced significant improvement in the physical function subdomain and in the quality of life of patients.<a class="elsevierStyleCrossRefs" href="#bib0140">28–30</a> This improvement occurred more frequently in patients with a worse baseline physical function, fewer comorbidities and shorter duration of symptoms.Retention rates (days of treatment without abandonment) of NSAIDs, especially COXIB remain high, particularly in chronically ill and patients over 65 years. The average duration of treatment in rheumatic patients for celecoxib, rofecoxib, naproxen and ibuprofen was 15, 13, 10 and 10months, respectively.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Differences in safety, especially GI, could have significant implications for the quality of life of patients.<a class="elsevierStyleCrossRefs" href="#bib0155">31,32</a>Cardiovascular RiskStratification of Vascular Risk<elsevierMultimedia ident="tb0030"></elsevierMultimedia>Given the CV risk associated with NSAID therapy, it is important to evaluate this parameter when prescribing it and choosing it as an appropriate treatment. The Third Joint Task Force on Cardiovascular Disease Prevention in Clinical Practice recommended a Systematic Coronary Risk Evaluation (SCORE) model for CV risk estimation in Europe,<a class="elsevierStyleCrossRef" href="#bib0165">33</a> which is based on studies on European population. Given the geographic variability of CV risk in Europe, 2 SCORE models have been developed, for countries with high or low risk, setting Spain in the low incidence zone.<a class="elsevierStyleCrossRefs" href="#bib0170">34,35</a>The CV risk is stratified into very high, high, moderate or low CV risk<a class="elsevierStyleCrossRefs" href="#bib0180">36,37</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). This new classification of CV risk levels is directly related to the achievement of therapeutic goals over increasingly stringent classic CV risk factors. Thus, specifically defined lipid goals are 70mg/dL in plasma LDL-cholesterol levels for patients at very high CV risk 100mg/dL for high-risk patients and 115hp mg/dL in patients with moderate CV risk.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The first “EULAR Standing Committee for International Clinical Studies Including Therapeutics” consensus for CV risk management in patients with rheumatoid arthritis and other inflammatory arthritis (spondyloarthropathy) was published in 2010. These diseases, in particular rheumatoid arthritis, have been linked directly to an increased cardiovascular risk and long-term cardiovascular mortality. This consensus recommends evaluating CV risk through the modified SCORE chart (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), and proposes a Decalogue of recommendations based on scientific evidence.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> In the general aspects of estimation and CV risk management, these recommendations could also be extended to patients with osteoarthritis.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>Cardiovascular Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs<elsevierMultimedia ident="tb0035"></elsevierMultimedia>In the absence of treatment, administration of NSAIDs increases the risk of ACS or other CV atherothrombotic problems. The clinical trials that determined the association between NSAIDs and CV events were not specifically designed for this purpose.<a class="elsevierStyleCrossRefs" href="#bib0195">39,40</a> Observational studies and meta-analyses of observational and clinical trials indicate that all NSAIDs increase the CV risk although to varying and, in general, low degrees. A recently conducted review by the Spanish Agency for Medicines and Health Products (AEMPS) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA)<a class="elsevierStyleCrossRef" href="#bib0205">41</a> has concluded that recent evidence confirms previous findings published in 2006, which showed an increased CV risk of atherothrombotic type for NSAIDs, although the risk/benefit balance remains positive.<elsevierMultimedia ident="tb0040"></elsevierMultimedia>Different meta-analyses have indicated to a greater or lesser extent that all NSAIDs studied increased CV risk, although the absolute magnitude is limited.<a class="elsevierStyleCrossRefs" href="#bib0210">42,43</a> A meta-analysis of observational studies published by McGettigan and Henry<a class="elsevierStyleCrossRef" href="#bib0220">44</a> in populations with high CV risk studied the most currently used NSAIDS (naproxen, ibuprofen, celecoxib, diclofenac, indomethacin, piroxicam, meloxicam, etodolac, etoricoxib and valdecoxib). The overall conclusions of the review suggested that naproxen and low doses of ibuprofen are associated with smaller increases in CV risk. Diclofenac clearly increased CV risk. The data for etoricoxib are sparse, but comparisons with naproxen and ibuprofen showed a higher CV risk. Indomethacin was also associated with a significant increase in CV risk. In the MEDAL study, etoricoxib was associated to a CV risk equal to that of diclofenac.<a class="elsevierStyleCrossRef" href="#bib0225">45</a>The most recent large meta-analysis of clinical trials with individual patient data indicates that NSAIDs and coxibs have increased CV risk compared to placebo, with no significant differences between them globally. Among the nonselective NSAIDs, CV risk was higher with diclofenac, which presented a similar risk to that of coxibs. Naproxen meanwhile, at doses of 500mg/12h, was not associated with increased CV risk, unlike ibuprofen and diclofenac, the only nonselective NSAIDs most studied.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> There is also a clear association between the risk of developing heart failure and the administration of these drugs<a class="elsevierStyleCrossRef" href="#bib0230">46</a> in addition to the well-known relationship of NSAIDs and the development of episodes or exacerbations of heart failure.Patients with ischemic heart disease have a higher risk of CV events when given NSAIDs. A Spanish<a class="elsevierStyleCrossRef" href="#bib0235">47</a> case–control study, which included 6000 participants concluded that NSAID use is associated with an overall increase of 16% in coronary risk (OR: 1.16, 95% CI: 0.95–1.42). The use of high doses increased it by 64% (OR: 1.64, 95% CI: 1.06–2.53) compared to those taking low doses. In patients with ischemic heart disease, the increased risk was 84% (OR: 1.84, 95% CI: 1.13–3.00). The meta-analysis of<a class="elsevierStyleCrossRef" href="#bib0220">44</a> McGettigan and Henry also supports the fact that high doses are associated with increased risk.Anticoagulant Use<elsevierMultimedia ident="tb0045"></elsevierMultimedia>Evidence through observational studies showing an increased risk of upper gastrointestinal bleeding in patients using NSAIDs and anticoagulants is extensive. In general, NSAIDs should be avoided in patients using these drugs.<a class="elsevierStyleCrossRefs" href="#bib0240">48–51</a> The safety of novel anticoagulants such as dabigatran, rivaroxaban and apixaban associated with NSAIDs does not seem different from the classical anticoagulants.<a class="elsevierStyleCrossRef" href="#bib0260">52</a>Interactions with anticoagulants are different for different NSAIDs. Aspirin, phenylbutazone and mefenamic acid very significantly enhance the anticoagulant effect of warfarin, displacing albumin and decreasing its metabolism in the liver.<a class="elsevierStyleCrossRef" href="#bib0265">53</a> Tenoxicam, meloxicam, lornoxicam, nimesulide, etodolac, nabumetone and celecoxib did not significantly increase the international normalized ratio (INR) in anticoagulated individuals. Conversely, diclofenac, ibuprofen and naproxen increased bleeding time.<a class="elsevierStyleCrossRefs" href="#bib0270">54–56</a>A study that evaluated 98,821 elderly patients on continuous treatment with warfarin indicated that the risk of upper gastrointestinal bleeding associated with NSAIDs or coxibs was similar.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> However, more recent studies have indicated that celecoxib combined with warfarin was associated with lower risk of GI bleeding hospitalizations than the association of warfarin with ibuprofen, indomethacin, etodolac, nabumetone and naproxen.<a class="elsevierStyleCrossRefs" href="#bib0290">58,59</a> All this means that, even with reservations, COXIBs should be considered as a first choice in situations where an NSAID is needed and the problem cannot be handled using other therapies.Use of Antiplatelet Agents<elsevierMultimedia ident="tb0050"></elsevierMultimedia>Ibuprofen, naproxen and indomethacin, but not paracetamol, diclofenac or coxibs, interfere with aspirins ability to irreversibly acetylate the platelet COX-1 enzyme, so it is likely that these drugs reduce the protective effect of aspirin on the risk of atherosclerotic events.<a class="elsevierStyleCrossRefs" href="#bib0300">60–62</a>The evidence is not yet sufficient to make firm recommendations.<a class="elsevierStyleCrossRef" href="#bib0315">63</a> However, ibuprofen should not be taken until at least 1h after ingestion of aspirin. For patients taking enteric coated-ASA (mostly in Spain) the problem is greater because the peak maximum release is late (beyond 4h), which makes interaction with ibuprofen is very likely. Thus, a study showed that the antiplatelet effect of low dose enteric coated aspirin is attenuated when ibuprofen is administered 2, 7 and 12h after ASA.<a class="elsevierStyleCrossRefs" href="#bib0320">64,65</a> In the case of naproxen, interaction was lower when administered at least 2h after ASA.<a class="elsevierStyleCrossRef" href="#bib0330">66</a> There is controversy about the extent to which this interaction may have clinical impact in terms of CV mortality in patients taking aspirin and ibuprofen, as the 2 studies are contradictory.<a class="elsevierStyleCrossRefs" href="#bib0335">67,68</a><elsevierMultimedia ident="tb0055"></elsevierMultimedia>Celecoxib, rofecoxib, and lumiracoxib do not interfere with ASA in its ability to irreversibly acetylate platelet COX-1.<a class="elsevierStyleCrossRefs" href="#bib0300">60,69</a> Of these, only celecoxib is available in the market, which reduces the options, as there are no data for etoricoxib. The trouble with using ASA and COXIB is determined by the CV risk associated with them and the fact that the EMA, but not the FDA, established a contraindication to the use of coxibs in patients with previous history of CV events. This limits considerably the treatment options in this population, given also that naproxen, although neutral from the point of view CV risk at doses of 500mg/12h, is associated with increased GI risk and may interfere with ASA. So, in patients with ASA who have not presented a CV event, celecoxib at low doses and for the shortest possible time is a reasonable therapeutic option based on epidemiological studies indicating that the drug has no greater risk than other traditional NSAIDs.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> Prescribing recommendations according to CV and GI risk are developed in the algorithm of the attached as <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Gastrointestinal RiskDigestive Risk Stratification<elsevierMultimedia ident="tb0060"></elsevierMultimedia>The keys for this custom evaluation are those outlined in this section. The risk profile is established for each patient according to <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and will be the one to guide prevention strategy.<elsevierMultimedia ident="tb0065"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>As age increases, the risk of developing GI complications in patients taking NSAIDs also increases progressively.<a class="elsevierStyleCrossRefs" href="#bib0350">70,71</a> Patients over 60 years of age alone is a risk factor for the occurrence of GI complications, and this risk is increased in patients receiving NSAIDs.<a class="elsevierStyleCrossRefs" href="#bib0360">72,73</a> It is estimated that approximately 6 upper GI complications occur per 1000 persons/year in patients taking NSAIDs and with an age between 60 and 69years. This estimate increases to 16 per 1000persons/year in patients aged between 70 and 79 years.<elsevierMultimedia ident="tb0070"></elsevierMultimedia>The existence of a previous history of uncomplicated gastric or duodenal ulcer or a history of GI bleeding or perforation is an independent risk factor for the development of peptic ulcer complications associated with taking NSAIDs. This finding has been confirmed in most observational studies and clinical trials.<a class="elsevierStyleCrossRefs" href="#bib0255">51,71,74–79</a><elsevierMultimedia ident="tb0075"></elsevierMultimedia>The combination of 2 or more NSAIDs increases the risk of bleeding over the individual risk for each individual NSAIDs.<a class="elsevierStyleCrossRef" href="#bib0400">80</a> Similarly, and possibly linked to this same phenomenon, it has been noted that the change of an NSAID to another during an episode also increases the risk of upper GI bleeding.<a class="elsevierStyleCrossRef" href="#bib0405">81</a>This increased risk with the combination of 2 NSAIDs is also observed with the combination of a classic NSAIDs or coxibs with aspirin at low doses used for preventing CV events, currently the most commonly used combination. In the CLASS study<a class="elsevierStyleCrossRef" href="#bib0410">82</a> patients who received a classic NSAID plus low-dose ASA had an annualized complication rate of 2.1%, higher than that seen in patients receiving NSAIDs alone (1.2%). A number of observational studies have shown that the combination of NSAIDs or coxibs with aspirin increases the risk of upper gastrointestinal bleeding over the risk estimates for each of the drugs individually.<a class="elsevierStyleCrossRefs" href="#bib0405">81,83,84</a> Post hoc analysis comparisons of nonrandomized and observational studies have suggested that the risk associated with traditional NSAID combination+ASA is possibly greater than that associated with COXIB+ASA.<a class="elsevierStyleCrossRefs" href="#bib0425">85,86</a>Finally, the concomitant use of steroids has been included in some previous reviews among arisk factors for GI complications. However, the latest evidence shows that the incidence of complications is very low, so it cannot be established that this combination of drugs constitutes an essential GI risk factor of.<a class="elsevierStyleCrossRefs" href="#bib0435">87,88</a><elsevierMultimedia ident="tb0080"></elsevierMultimedia>High GI risk complication in patients treated with NSAIDs is dose dependent. While it has been suggested that the risk of developing high GI complications is higher during the first month of treatment and then stays stable during the remaining period of treatment, long-term clinical trials indicate that the risk of developing complications is stable throughout time.<a class="elsevierStyleCrossRef" href="#bib0445">89</a><elsevierMultimedia ident="tb0085"></elsevierMultimedia>A study in patients with prior acute myocardial infarction noted that short-term treatment with most NSAIDs is associated with an increased CV risk. Diclofenac was associated with an increased CV risk from the onset of treatment to its end. Ibuprofen also showed an increased risk when used for more than a week. Celecoxib was associated with increased risk of death after a treatment duration of 14–30days. Naproxen was the only NSAID evaluated that was not associated with an increased risk of heart attack or death.<a class="elsevierStyleCrossRef" href="#bib0450">90</a>There is no strong evidence that the use of acetaminophen is associated with increased cardiovascular risk.<a class="elsevierStyleCrossRef" href="#bib0455">91</a>Gastrointestinal Complications Associated With the Use of NSAIDs<elsevierMultimedia ident="tb0090"></elsevierMultimedia>NSAID treatment is associated with serious adverse events which affect the upper and lower gastrointestinal tract. They can occur as uncomplicated symptomatic ulcers or upper gastrointestinal bleeding, lower GI bleeding and GI perforation. These side effects occur in the 1%–4% of patients treated with NSAIDs.<a class="elsevierStyleCrossRef" href="#bib0410">82</a> The relative risk for developing serious upper GI complications in patients treated with NSAIDs has been estimated between 3 and 5 times compared to those untreated.<a class="elsevierStyleCrossRef" href="#bib0460">92</a>The incidence of serious complications of the lower digestive tract is not well defined, but it could account for 20% of the morbidity associated with NSAIDs.<a class="elsevierStyleCrossRef" href="#bib0465">93</a> Studies show that 70% of patients taking NSAIDs chronically develop lesions of the lower GI tract, although many of them have little clinical relevance. Among the lesions described, increased intestinal permeability, inflammation, erosions, ulcers, strictures, anemia, protein losing enteropathy, diverticulitis, bleeding and perforation are included. Recent data on the rate of upper and lower GI perforation in patients with rheumatoid arthritis show that 83% occur in the lower tract.<a class="elsevierStyleCrossRef" href="#bib0470">94</a> Additionally, some patients with certain rheumatic of inflammatory diseases also have associated inflammatory bowel disease, often subclinical, that possibly, but not exclusively be due to chronic NSAID use.Prevention Strategies<elsevierMultimedia ident="tb0095"></elsevierMultimedia>H2 antagonists have been shown to be inferior to proton pump inhibitors (PPI), in both healing and prevention of ulcers associated with NSAID or ASA use.<a class="elsevierStyleCrossRefs" href="#bib0475">95–99</a><elsevierMultimedia ident="tb0100"></elsevierMultimedia>PPIs have been shown to be superior to H2 antagonists for the prevention of NSAID-induced endoscopic ulcers and similar to misoprostol,<a class="elsevierStyleCrossRefs" href="#bib0500">100,101</a> but better tolerated. Observational studies and clinical trials have suggested that PPIs reduce the risk of GI complications in patients taking NSAIDs.<a class="elsevierStyleCrossRefs" href="#bib0130">26,53,71,76</a><elsevierMultimedia ident="tb0105"></elsevierMultimedia>Coxibs have been proven superior to the combination of NSAID plus placebo and as effective as the use of nonselective NSAID associated to PPIs for the prevention of GI lesions and<a class="elsevierStyleCrossRefs" href="#bib0345">69,82,102–105</a> complications. Data from randomized trials indicate that coxibs are associated with a lower frequency of low GI lesions produced by the association of a nonselective NSAID plus PPI.<a class="elsevierStyleCrossRefs" href="#bib0515">103,106,107</a><elsevierMultimedia ident="tb0110"></elsevierMultimedia>These drugs have been developed with the intent of reducing GI toxicity associated with NSAID use. Several meta-analyses have indicated that the risk of upper GI complications with COXIB was 50% less than the risk seen with conventional NSAIDs.<a class="elsevierStyleCrossRefs" href="#bib0425">85,108</a>The CONDOR and GI REASON studies, meanwhile, have shown that celecoxib was associated with a lower frequency and a reduction in all clinically significant episodes of GI tract toxicity when compared to PPI and associated diclofenac (CONDOR) or traditional NSAIDs associated or not to PPI (GI REASON).<a class="elsevierStyleCrossRefs" href="#bib0535">107,109</a> One study showed a lower (not significant) rate of complications with etoricoxib versus diclofenac.<a class="elsevierStyleCrossRef" href="#bib0550">110</a> The MEDAL study indicates in turn that etoricoxib was not superior to diclofenac regarding the incidence of upper and lower GI complications.<a class="elsevierStyleCrossRef" href="#bib0550">110</a><elsevierMultimedia ident="tb0115"></elsevierMultimedia>Antiplatelet doses of aspirin doubles the risk of GI bleeding and hospitalization compared to people who do not use it.<a class="elsevierStyleCrossRef" href="#bib0460">92</a> This causes different clinical situations in patients with CV and GI risk, and doubts may arise between maintaining or interrupting treatment with ASA. Such disruption can precipitate serious CV effects, including death.<a class="elsevierStyleCrossRefs" href="#bib0555">111,112</a>ASA therapy is associated with the development of peptic ulcers, including esophageal, gastroesophageal reflux disease (GERD) or dyspepsia, besides upper GI complications. Therefore, the benefits of treatment with PPIs in patients taking ASA also extend to a better control of symptoms and lesions associated with GERD.<a class="elsevierStyleCrossRef" href="#bib0565">113</a>Recent data indicate that the combined use of PPI, low dose aspirin and clopidogrel in patients with CV risk is associated with a low frequency of GI bleeding (1.8 cases per 100 patient-years). However, a shift in the location thereof to the lower GI tract is observed since, for all bleeding episodes, 73% were found in the small intestine and in the colon (many of them as a result of vascular injury, possibly preexisting). These hemorrhages occurred predominantly at an early stage during the first year of follow up.<a class="elsevierStyleCrossRef" href="#bib0570">114</a>Liver Risk<elsevierMultimedia ident="tb0120"></elsevierMultimedia>Several systematic reviews assessing patients in clinical trials show a very low incidence of serious hepatic effects associated with NSAID use. A systematic review including 132 studies shows that the need to discontinue NSAID due to adverse effects was not significantly higher than the placebo group, except for diclofenac.<a class="elsevierStyleCrossRef" href="#bib0575">115</a> Another analysis that brings together 41 studies showed the incidence of hepatic adverse effects of celecoxib to be 1.1%, 4.2% for diclofenac, 1.5% for ibuprofen and 0.9% for placebo<a class="elsevierStyleCrossRef" href="#bib0580">116</a>; the rate of serious hepatic adverse events was 5/100000 for celecoxib and 21/100000 for diclofenac. The need for hospitalization due to toxicity has been estimated at between 3 and 23 per 100000 patients.<a class="elsevierStyleCrossRefs" href="#bib0585">117,118</a> Transient elevations of transaminases are common, and in most cases do not progress.<a class="elsevierStyleCrossRef" href="#bib0575">115</a> Although cases of toxic hepatitis, and even cases of severe hepatitis and death have been described due to NSAID,<a class="elsevierStyleCrossRefs" href="#bib0575">115,119–122</a> these are exceptional, and there is no monitoring system to determine which patients will have a serious adverse liver reaction, so monitoring measures are not recommended. The risk of liver toxicity is significantly increased with diclofenac than with other NSAIDs.<a class="elsevierStyleCrossRefs" href="#bib0575">115,116</a><elsevierMultimedia ident="tb0125"></elsevierMultimedia>The use of NSAIDs in patients with cirrhosis has been linked to the onset of variceal bleeding,<a class="elsevierStyleCrossRef" href="#bib0615">123</a> and it is well known for his ability to impair renal function in patients with both compensated and decompensated liver cirrhosis.<a class="elsevierStyleCrossRefs" href="#bib0620">124,125</a> For these reasons NSAIDs are considered contraindicated in patients with chronic liver disease and cirrhosis.<elsevierMultimedia ident="tb0130"></elsevierMultimedia>A study in 28 patients with cirrhosis and ascites assessed for 3 days the effect of celecoxib 200mg every 12h, naproxen 500mg every 12h placebo on renal function and platelet aggregation. Neither celecoxib nor placebo induced changes in renal or platelet function. In contrast, naproxen induced a marked reduction in glomerular filtration, renal plasma flow and urine output, along with a significant antiplatelet effect.<a class="elsevierStyleCrossRef" href="#bib0630">126</a> On the other hand, Agrawal et al. noted that etoricoxib<a class="elsevierStyleCrossRef" href="#bib0635">127</a> was well tolerated in patients with moderate or severe hepatic impairment. However, given the limited experience, it is also recommended to avoid the use of coxibs in patients with liver disease, and especially if presenting decompensated liver cirrhosis.Dyspepsia<elsevierMultimedia ident="tb0135"></elsevierMultimedia>It is estimated that between 10% and 30% of patients receiving NSAIDs have dyspepsia, and dyspepsia leads to discontinuation of treatment in 5%–15% of patients.<a class="elsevierStyleCrossRef" href="#bib0640">128</a> The addition of a PPI versus placebo was associated with a lower frequency of dyspepsia in<a class="elsevierStyleCrossRef" href="#bib0505">101</a> patients treated with NSAIDs. A meta-analysis by Spiegel et al.,<a class="elsevierStyleCrossRef" href="#bib0645">129</a> evaluated 26 studies comparing a COXIB vs traditional NSAIDs or traditional NSAID plus PPI vs NSAIDs alone. Comparing COXIB vs traditional NSAIDs showed a relative risk reduction of symptoms of 12% and an absolute reduction of 3.7%. Comparison of traditional NSAIDs {3+} PPI vs traditional NSAIDs showed a relative risk reduction of 66% and an absolute risk reduction of 9%. The number needed to treat to prevent dyspepsia was 27 for coxibs and 11 for traditional NSAIDs plus PPI. These results should be evaluated carefully, since a direct comparison between coxibs and traditional NSAIDs+PPI was not made. In an ad hoc systematic search performed, 6 studies directly comparing with a traditional NSAID COXIB+PPI were found.<a class="elsevierStyleCrossRefs" href="#bib0510">102,103,106,130–132</a> The meta-analysis of 6 studies with data on dyspepsia suggests, however, that this effect is true. Dyspepsia incidence was 11.8% (112/947) in those receiving one COXIB vs 7.4% (72/977) in patients treated with a traditional or nonselective NSAIDs+PPI (OR: 2.2, 95% CI: 1.3–3.6). Given the high efficacy of PPIs in the treatment of dyspepsia associated with NSAIDs, it seems reasonable to recommend their use in the case of patients having dyspepsia associated with the use of coxibs.Inflammatory Bowel Disease<elsevierMultimedia ident="tb0140"></elsevierMultimedia>It is estimated that up to one-third of patients with IBD develop arthritis which may or may not be linked<a class="elsevierStyleCrossRef" href="#bib0665">133</a> pathogenically with the disease. This implies that many patients with IBD require some type of NSAID at any given point in their evolution. Existing epidemiological studies are generally of poor quality and results clearly contradictory.<a class="elsevierStyleCrossRefs" href="#bib0670">134–136</a> Moreover, there are no clinical trials to show that taking NSAIDs produce worsening or recurrence of IBD, although there are case series with varying numbers of patients that do suggest it.<a class="elsevierStyleCrossRef" href="#bib0670">134</a> In this sense, a relatively recent study indicated that 17%–28% of patients in remission with Crohn's disease or ulcerative colitis who received nonselective NSAIDs such as naproxen, diclofenac, indomethacin or nabumetone for 4 weeks, had recurrence in the first 9days after taking the drug. This did not occur in those taking nimesulide (selective inhibitor of COX-2), low-dose aspirin or paracetamol.<a class="elsevierStyleCrossRef" href="#bib0685">137</a> Few clinical trials have tested whether the use of selective COX-2 inhibitors is associated with quiescent IBD relapses. A double-blind randomized trial compared etoricoxib (60–120mg/day) versus placebo over a period of 3months in patients with Crohn's disease or ulcerative colitis. The recurrence rate was 10% in both situations.<a class="elsevierStyleCrossRef" href="#bib0690">138</a> In another similar trial, but with a shorter observation period of 14 days celecoxib 200mg/12h was compared to placebo in patients with ulcerative colitis, with the same recurrence rates below 3%.<a class="elsevierStyleCrossRef" href="#bib0695">139</a>Renal RiskRenal Risk Stratification<elsevierMultimedia ident="tb0145"></elsevierMultimedia>NSAIDs interfere with renal homeostasis. This has implications for renal function, known in classic NSAIDs, which as a result of the most recent investigations have been better defined in COXIBs. Systematic reviews of the risk of developing renal comorbidity in rheumatic patients have difficulty concluding on the magnitude of the problem, because clinical trials do not measure systematically renal outcomes or as part of the primary events of interest.<a class="elsevierStyleCrossRefs" href="#bib0700">140–142</a>The Spanish Society of Nephrology recommended an annual estimate of renal function by glomerular filtration. Accordingly, the presence of chronic renal disease is categorized according to <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<a class="elsevierStyleCrossRef" href="#bib0715">143</a> A moderate risk of developing renal adverse event is present if patients have chronic kidney disease stage 3 and/or intravascular volume depletion, hypertension or congestive heart failure and peripheral edema is.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Stages 4 and 5 are considered at high risk of developing renal adverse event.Renal Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs<elsevierMultimedia ident="tb0150"></elsevierMultimedia>NSAIDs lead to a decreased renal function and sodium and water retention. Clinically, this may present as elevated serum creatinine, edema, hypertension, water and electrolyte imbalance, renal failure, renal papillary necrosis or nephrotic syndrome.<a class="elsevierStyleCrossRef" href="#bib0700">140</a> The relative risk of renal adverse event is different for each type of NSAID, and apparently there is no class effect. As with other toxic effects, these are dose dependent and accumulate over time. Moreover, in rheumatic patients renal and CV comorbidities are often associated, which increases the risk.<a class="elsevierStyleCrossRefs" href="#bib0700">140,141,144</a>Decreased renal function (elevated serum creatinine>1.3 times the upper normal limit) occurs with a frequency of 1%. This elevation was observed equally in patients receiving therapeutic doses of NSAIDs, and is higher with NSAIDs than placebo.Another clinically relevant side effect associated with NSAIDs is the development of peripheral edema, with an estimated risk of 3%. This risk is even greater when COXIBs are used than with placebo (5%–38% higher in clinical trials in which edema is a major variable in the research). However, celecoxib at doses of 200mg/day was not associated with increased risk of edema.<a class="elsevierStyleCrossRef" href="#bib0725">145</a> This suggests that the presence of edema does not follow a specific effect of the coxib class. The development of heart failure due to the retention of sodium and water in susceptible patients is another common side effect of all NSAIDs.<a class="elsevierStyleCrossRef" href="#bib0350">70</a>All NSAIDs are associated with increased blood pressure in hypertensive subjects, and this has little effect in individuals with normal blood pressure. In general, the frequency of hypertension associated with NSAIDs is ≈2% and occurs more frequently in subjects with renal comorbidity and/or pre-existing CV disease. The minimum mean change in blood pressure after initiation of NSAID is an elevation of 5mmHg but the clinical significance of this increase is uncertain. The risk is higher for coxibs (rofecoxib>etoricoxib and lower for celecoxib). It is important to monitor blood pressure after initiation of NSAID, especially in the elderly, in patients with pre-hypertension and in patients with chronic renal disease. The use of NSAIDs is contraindicated in patients with uncontrolled hypertension.<a class="elsevierStyleCrossRefs" href="#bib0730">146–148</a>The presence of severe renal damage associated with NSAIDs is a rare event, with little information about its occurrence and risk factors.Other Relevant AspectsAnemia<elsevierMultimedia ident="tb0155"></elsevierMultimedia>NSAID use is associated with GI bleeding made clinically apparent by hematemesis, melena or rectal bleeding, but also hidden GI bleeding and anemia. The origin of this occult blood loss may be due to mucosal lesions that affect the entire GI tract, from the stomach to the small intestine and the colon.<a class="elsevierStyleCrossRef" href="#bib0745">149</a> Different studies in healthy volunteers have demonstrated the appearance of petechiae, intraluminal blood and mucous substance losses compatible with erosions and ulcers in the small intestine. In these studies it has been observed that ibuprofen or naproxen with a PPI were more associated with these injuries than celecoxib at doses of 400mg/day or placebo.<a class="elsevierStyleCrossRefs" href="#bib0530">106,107</a> In patients on chronic NSAIDs or coxibs it has also been seen, by capsule endoscopy, that 40%<a class="elsevierStyleCrossRefs" href="#bib0750">150,151</a> of them had lesions in the small intestine, although the frequency was numerically lower in patients treated with coxibs. The CONDOR<a class="elsevierStyleCrossRef" href="#bib0515">103</a> study showed that patients with osteoarthritis or rheumatoid arthritis treated with celecoxib 200mg/12h had 4 times the risk of developing lower hematocrit or hemoglogin decreases (>2g/dL) of GI origin or, presumably, from the small bowel versus diclofenac 75mg/12h plus omeprazole 20mg/day after 6 months of treatment. This study has been confirmed by another randomized multicenter study, the PROBE trial, designed to compare celecoxib versus traditional NSAIDs associated or not to PPI.<a class="elsevierStyleCrossRef" href="#bib0760">152</a> In the MEDAL program, however, no significant difference between diclofenac etoricoxib and the number of GI tract complications was observed.<a class="elsevierStyleCrossRef" href="#bib0550">110</a>Postoperative<elsevierMultimedia ident="tb0160"></elsevierMultimedia>The non-opioid analgesics, paracetamol and NSAIDs are often given with opioids as part of multimodal analgesia after major surgery. The choice of method of postoperative pain relief should be well balanced and combining different drugs and different routes of administration may be employed with the aim of using smaller doses to minimize potential side effects.A recent systematic review<a class="elsevierStyleCrossRef" href="#bib0765">153</a> demonstrated a statistically significant reduction in morphine consumption at 24h after surgery, when using combination therapy with acetaminophen or NSAIDs versus placebo; there was also a clear difference between paracetamol and NSAIDs, in favor of the latter. A statistically significant difference was also shown in the level of sedation and the occurrence of adverse effects (post operative nausea and vomiting) with any of the combinations, with no superiority of one over another. In another review<a class="elsevierStyleCrossRef" href="#bib0770">154</a> renal function was evaluated after administration of NSAIDs for postoperative pain control. In 1459 patients from 23 randomized trials, creatinine clearance (48h), serum creatinine, urine volume, Na/K urinary and need for dialysis were determined. The results show a decrease in creatinine clearance 16ml/min but no differences in other parameters. Nor difference was seen between NSAIDs or cases of renal failure requiring dialysis were observed.A single oral dose of celecoxib or etoricoxib<a class="elsevierStyleCrossRefs" href="#bib0775">155,156</a> (120mg) is effective for postoperative pain relief and adverse events did not differ from placebo.Dexketoprofen administered parenterally has a similar analgesic efficacy as postoperative ketoprofen and diclofenac.<a class="elsevierStyleCrossRefs" href="#bib0785">157,158</a> The recommended dose is 50mg every 8or 12h limited to the acute symptomatic period (no more than 2days). The total daily dose should be limited to 50mg on the following assumptions: (a) in the elderly who have a mild physiological decline in renal function, (b) in patients with mild to moderate hepatic impairment (Child–Pugh score 5–9), which also should be carefully monitored, and (c) for mild renal impairment (creatinine clearance 50–80ml/min).Summary and Final RecommendationsA summary of the recommendations of this consensus, and the graphic expression of the secondary effects of commonly used NSAIDs are detailed in <a class="elsevierStyleCrossRefs" href="#tbl0025">Tables 5 and 6</a>. Finally, in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a> an algorithm guiding the correct prescription of NSAIDs, based on the presence of different levels of GI and CV risk has been constructed, according to the evidence available in 2013.<elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia>Ethical ResponsibilitiesProtection of people and animalsThe authors declare that no experiments have been performed on humans or animals.Data confidentialityThe authors state that no patient data appear in this article.Right to privacy and informed consentThe authors state that no patient data appear in this article.Conflicts of InterestDr. Lanas claims to have received research grants from AstraZeneca, Pfizer and Bayer over the past two years. He has also participated in Advisory Board meetings organized by Pfizer and Bayer.Dr. Calvet states he has participated, for the past two years, in Boards organized by Pfizer.Dr. P. Benito claims to have received, over the past two years, research grants from Pfizer, Abbott, Roche, UCB and Esteve.Dr. García Llorente states that he has participated, for the past two years, at scientific meetings sponsored by Abbott, Pfeizer, UCB, Roche, BMS, as well as a UCB advisory board.Dr. Blanca Hernández Cruz states that in the past two years she has received research grants, consulting fees paid and fee-for-papers with various companies, the Spanish Society of Rheumatology, Abbott, Roche, Pfizer, MSD and BMS.The rest of the participants declared no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres326266" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec307747" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres326267" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec307746" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Operational Definitions of the Document" ] ] ] 5 => array:3 [ "identificador" => "sec0015" "titulo" => "Methodology" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Nominal Group" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Drafting of Recommendations" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Delphi Survey" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Recommendations" "secciones" => array:5 [ 0 => array:3 [ "identificador" => "sec0040" "titulo" => "Efficacy" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Directions" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Time of Use" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Quality of Life" ] ] ] 1 => array:3 [ "identificador" => "sec0060" "titulo" => "Cardiovascular Risk" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Stratification of Vascular Risk" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Cardiovascular Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Anticoagulant Use" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "Use of Antiplatelet Agents" ] ] ] 2 => array:3 [ "identificador" => "sec0085" "titulo" => "Gastrointestinal Risk" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Digestive Risk Stratification" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Gastrointestinal Complications Associated With the Use of NSAIDs" ] 2 => array:2 [ "identificador" => "sec0100" "titulo" => "Prevention Strategies" ] 3 => array:2 [ "identificador" => "sec0105" "titulo" => "Liver Risk" ] 4 => array:2 [ "identificador" => "sec0110" "titulo" => "Dyspepsia" ] 5 => array:2 [ "identificador" => "sec0115" "titulo" => "Inflammatory Bowel Disease" ] ] ] 3 => array:3 [ "identificador" => "sec0120" "titulo" => "Renal Risk" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0125" "titulo" => "Renal Risk Stratification" ] 1 => array:2 [ "identificador" => "sec0130" "titulo" => "Renal Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs" ] ] ] 4 => array:3 [ "identificador" => "sec0135" "titulo" => "Other Relevant Aspects" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0140" "titulo" => "Anemia" ] 1 => array:2 [ "identificador" => "sec0145" "titulo" => "Postoperative" ] ] ] ] ] 7 => array:2 [ "identificador" => "sec0150" "titulo" => "Summary and Final Recommendations" ] 8 => array:3 [ "identificador" => "sec0155" "titulo" => "Ethical Responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0160" "titulo" => "Protection of people and animals" ] 1 => array:2 [ "identificador" => "sec0165" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0170" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0175" "titulo" => "Conflicts of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-07-31" "fechaAceptado" => "2013-10-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec307747" "palabras" => array:5 [ 0 => "Non steroidal anti-inflammatory drugs" 1 => "Cardiovascular" 2 => "Peptic ulcer" 3 => "Gastrointestinal hemorrhage" 4 => "Adverse event" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec307746" "palabras" => array:5 [ 0 => "Anti-inflamatorios no esteroideos" 1 => "Cardiovascular" 2 => "Úlcera péptica" 3 => "Hemorragia gastrointestinal" 4 => "Efecto adverso" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems. These recommendations are based on current scientific evidence, and takes into consideration gastrointestinal and cardiovascular safety issues. The recommendations have been agreed on by experts from three scientific societies (Spanish Society of Rheumatology [SER], Spanish Association of Gastroenterology [AEG] and Spanish Society of Cardiology [SEC]), following a two-round Delphi methodology. Areas that have been taken into account encompass: efficiency, cardiovascular risk, gastrointestinal risk, liver risk, renal risk, inflammatory bowel disease, anemia, post-operative pain, and prevention strategies. We propose a patient management algorithm that summarizes the main aspects of the recommendations." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Este artículo señala las recomendaciones claves para una adecuada prescripción de antiinflamatorios no esteroideos a pacientes que presentan indicación de tratamiento con esta medicación, en base a la evidencia científica actual y teniendo en consideración aspectos de seguridad gastrointestinal y cardiovascular. Las recomendaciones se han consensuado por expertos designados por 3 sociedades científicas (Sociedad Española de Reumatología, Asociación Española de Gastroenterología y Sociedad Española de Cardiología), siguiendo una metodología Delphi a 2 rondas. Las áreas que se han tenido en cuenta engloban: eficacia, riesgo cardiovascular, riesgo gastrointestinal, riesgo hepático, riesgo renal, enfermedad inflamatoria intestinal, anemia, dolor postoperatorio y estrategias de prevención. Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lanas A, Benito P, Alonso J, Hernández-Cruz B, Barón-Esquivias G, Perez-Aísa Á, et al. Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG). Reumatol Clin. 2014;10:68–84." ] 1 => array:2 [ "etiqueta" => "#" "nota" => "By agreement with the authors and the editors, this article is published in complete form simultaneouslyin the Journal Gastroenterología y Hepatología <a class="elsevierStyleInterRef" id="intr1005" href="http://dx.doi.org/10.1016/j.gastrohep.2013.11.014">doi:10.1016/j.gastrohep.2013.11.014</a>." ] ] "multimedia" => array:41 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1591 "Ancho" => 2489 "Tamanyo" => 196957 ] ] "descripcion" => array:1 [ "en" => "Diagram of the methodology for consensus." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2552 "Ancho" => 2878 "Tamanyo" => 637282 ] ] "descripcion" => array:1 [ "en" => "SCORE table calibrated for Spain. Estimated risk of atherosclerotic cardiovascular mortality at 10 years, for specific values of systolic blood pressure and total cholesterol, according to smoking status, gender and age." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2888 "Ancho" => 3277 "Tamanyo" => 268940 ] ] "descripcion" => array:1 [ "en" => "Algorithm recommendations for the use of NSAIDs according to the cardiovascular and gastrointestinal risk (upper and lower digestive tract). * If necessary naproxen+PPI or celecoxib at low doses (200mg/24h)±PPI as soon as possible in both cases. ** More robust information for celecoxib than for etoricoxib # Naproxen should be taken 2h before ASA. Ifenteric coated aspirin are used, interaction possibilities are greater. ## If there is a prior cardiovascular event, EMA and AEM currently contraindicate this option. It is assumed that patients with very high cardiovascular risk should be treated with ASA. Therefore, in the group of low gastrointestinal risk, very high cardiovascular risk is not contemplated, because use of ASA, and gastrointestinal risk is intermediate at best." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Paragraph \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Person responsible \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Introduction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Angel Lanas Arbeloa, Pere Benito Ruiz \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Methodology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Milena Gobbo Montoya \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Effectiveness</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Directions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pere Benito Ruiz \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Timing \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Francisco García Llorente \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Quality of life \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blanca Hernández Cruz \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular risk</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular risk stratification \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">José Ramón González-Juanatey \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated cardiovascular complications of NSAID use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Joaquín Martín Alonso \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of anticoagulants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gonzalo Barón Esquivas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Antiplatelet use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gonzalo Barón Esquivas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal risk</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Digestive risk stratification \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aisa Angeles Pérez \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal complications associated with the use of NSAIDs \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Aisa Angeles Pérez \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevention strategies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xavier Calvet Calvo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatic risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xavier Calvet Calvo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dyspepsia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xavier Calvet Calvo \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Angel Lanas Arbeloa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal risk</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal risk stratification \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blanca Hernández Cruz, Francisco García Llorente \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Associated renal complications of NSAID use \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Blanca Hernández Cruz, Francisco García Llorente \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other relevant aspects</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">José Ramón González-Juanatey, Angel Lanas Arbeloa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Postoperative \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gonzalo Barón Esquivas, Pere Benito Ruiz \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476186.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Sections of the Consensus and Person Responsible." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very high \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(a) Cardiovascular disease documented by invasive or non-invasive techniques (coronary angiography, isotope techniques, stress echocardiography and evidence of atherosclerotic plaques by carotid ultrasound), previous myocardial infarction, previous acute coronary syndrome, coronary revascularization, other revascularization procedures, stroke and peripheral arterial disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(b) Diabetes mellitus type 2 or type 1 diabetes mellitus associated with target organ damage (microalbuminuria: 30–300mg/24h) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(c) chronic moderate to severe renal disease (estimated glomerular filtration rate <60ml/min/l.73m2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(d) SCORE≥10% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(a) Any markedly elevated individual risk factor, familial hypercholesterolemia or severe hypertension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(b) ≥SCORE 5% and <10% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SCORE≥1% and <5% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SCORE<1% absence of other risk factors \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476188.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Assessment of Cardiovascular Risk." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Accepted risk factors: Age>60, history of complicated and uncomplicated peptic ulcer. Concomitant use of NSAIDs or aspirin plus COXIB with clopidogrel, anticoagulants, corticosteroids or inhibitors of serotonin reuptake, high dose NSAIDs, or 2 NSAID, serious comorbidity." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">History of complicated peptic ulcers \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of anticoagulants or \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Combination>2 other risk factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Medium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nonanticoagulated patients or those with a history of complicated ulcer who have some other isolated risk factor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients without risk factors. Does not take acetylsalicylic acid \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476189.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evaluation of Gastrointestinal Risk." ] ] 6 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "GFR, glomerular filtration rate; eGFR, estimated glomerular filtration rate." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Stage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">GFR (ml/min/1.73m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Description \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">≥90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kidney damage with normal GFR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60–89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Kidney damage, slight decrease in eGFR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30–59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate decrease in eGFR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15–29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serious decline in eGFR \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><15 or dialysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Predialysis/dialysis \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476185.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Estimation of Renal Damage." ] ] 7 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "The number of crosses indicates a semi-quantitative assessment of the level of risk vs non-use. The levels of evidence are not identical and sometimes limited (see specific recommendations).ASA, acetylsalicylic acid; ACO, anticoagulants; CV, cardiovascular; GI, gastrointestinal; PPI, proton pump inhibitors." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">NSAID type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Upper GI damage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Lower GI damage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Use of PPI to protect the upper GI tract \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Interaction with ASA or ACO \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">CV risk \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Diclofenac \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ibuprofen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Naproxen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">− \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Celecoxib \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">− \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Etoricoxib \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">++ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+ \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+++ \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476187.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of the Effects of Different NSAIDs at Anti-inflammatory Doses." ] ] 8 => array:7 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Recommendations \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Efficacy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Indications. The primary indication for the use of NSAIDs is to decrease pain. No NSAID has proven superior to another, with the efficacy of traditional NSAIDs being similar to that of COXIB \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Timing. Before using NSAIDs, other treatment options should be evaluated, and NSAIDs should always be prescribed at the lowest effective dose for the shortest possible time. Only in very specific cases, such as ankylosing spondylitis, continued long-term use may be justified \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Quality of life. NSAIDs cause an improvement in the quality of life of patients with chronic or acute rheumatic disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cardiovascular risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Cardiovascular risk stratification. All patients taking NSAIDs chronically should undergo an estimate of cardiovascular risk (CV) at least once a year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Cardiovascular complications associated with NSAID use. Administration of NSAIDs is associated with an increased risk of developing acute coronary syndrome (ACS) or other atherothrombotic cardiovascular events (stroke and peripheral arterial problems). The increased cardiovascular risk varies greatly depending on the type of NSAID used, naproxen being one of the safest, while rofecoxib, diclofenac, etodolac and indomethacin are associated with increased cardiovascular risk. Etoricoxib and diclofenac have a similar CV profile \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Use of anticoagulants. The combination of anticoagulants (warfarin, coumarin derivatives, etc.) and NSAIDs should be avoided. If absolutely necessary, COXIB appear to be associated with a lower risk of bleeding complications \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Use of antiplatelet. Avoid the use of NSAIDs, even in the short term in patients with acute myocardial infarction before taking ASA as it is associated with increased cardiovascular risk. In patients taking low-dose aspirin, the association with ibuprofen and naproxen interferes with the antiplatelet effect of aspirin, so one should avoid using them together. In patients taking aspirin to prevent cardiovascular events requiring chronic treatment with NSAIDs, coxibs are a therapeutic option to consider \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastrointestinal risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Gastrointestinal risk stratification. A custom profile assessment of baseline gastrointestinal risk of each patient and the NSAID to use should be performed. Patients over 60 years of age are a risk factor by themselves for the occurrence of gastrointestinal complications in patients taking NSAIDs, and this risk increases progressively with age. The presence of a history of gastroduodenal ulcer, complicated or uncomplicated peptic ulcer is a risk factor for the development of gastrointestinal complications in patients taking NSAIDs \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Gastrointestinal complications associated with NSAID use. It is not recommended to use two or more NSAID simultaneously, since there is increased efficiency and instead increases toxicity. The risk of gastrointestinal complications increases if high doses of NSAIDs are used in a sustained manner. This risk is constant regardless of the dose, for as long as the treatment is continued. NSAID use is associated with increased risk of lesion and complications of upper and lower gastrointestinal tract \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3. Prevention strategies. The use of H2-antagonist receptors for the prevention of gastrointestinal complications of NSAIDs is not recommended. The use of inhibitors of the proton pump (PPI) associated with a non-selective NSAID is a valid strategy for prevention of gastrointestinal complications of NSAIDs in patients at risk, with coxibs (celecoxib being the one with available data) being preferrable over the combination of a nonselective NSAID with a PPI in the prevention of gastrointestinal tract lesions. Using a COXIB reduces complications in the upper and lower gastrointestinal tract. The use of low dose aspirin increases 2–4 times the risk of complications, so patients with gastrointestinal risk factors should receive gastroprotection \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4. Hepatic risk. In patients treated with NSAIDs severe liver toxicity is rare and no special monitoring measures are recommended. In patients with liver cirrhosis avoidance of NSAIDs is recommended, and in the event that it becomes absolutely essential, the use of a COXIB is recommended for the shortest possible time \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5. Dyspepsia. In patients with dyspepsia associated with nonselective NSAIDs or coxibs, treatment with a PPI is recommended as the drug of choice \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6. Inflammatory bowel disease. In patients with inflammatory bowel disease, NSAIDs should be avoided, and if necessary, their use should be limited to quiescent phases of the disease, the use of coxibs is recommended at low doses and for a short time \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Renal risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Renal risk stratification. In chronic rheumatic disease patients receiving NSAIDs, renal function should be assessed by estimating glomerular filtration rate at least once a year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Renal complications associated with NSAID use. Patients with stage 3 chronic kidney disease, or associated renal and/or cardiovascular comorbidity, NSAIDs should not be used, except in special situations and with close clinical monitoring, and NSAID doses higher than those recommended should be avoided. In patients with CKD stages 4 and 5, the use of NSAIDs is contraindicated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other relevant aspects \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1. Anemia. The development of anemia or a hemoglobin decrease >2g/dL is common in patients who take NSAIDs, even if associated with PPI. Treatment with celecoxib is less likely to be associated with this side effect \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2. Postoperatively. We recommend the use of a paracetamol-NSAID combination for short term postoperative pain, provided there is no contraindication for the administration of the latter. One NSAID cannot be prioritized over another regarding their postoperative use. The combination in terms of dose and type of drug used in the postoperative period must be balanced empirically \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab476190.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of Consensus Recommendations." ] ] 9 => array:5 [ "identificador" => "tb0005" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The main indication for the use of NSAIDs is to decrease the pain.LE (Level of Evidence): 3, DR (degree of Recommendation): D, LA (Level of Agreement): 78%" ] ] 10 => array:5 [ "identificador" => "tb0010" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "No NSAID has been shown to be superior to another, and the efficacy of traditional NSAIDs is similar to that of coxibs.LE: 3, DR: D, LA: 100%" ] ] 11 => array:5 [ "identificador" => "tb0015" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "NSAIDs should be prescribed at the lowest effective dose and for the shortest possible time.LE: 1+, DR: A, LA: 100%In general, one should consider other treatment options before prescribing NSAIDs.LE 4, DR: D, LA: 89%" ] ] 12 => array:5 [ "identificador" => "tb0020" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The continued long-term use with NSAIDs may be justified in certain conditions, such as ankylosing spondylitis.LE: 2++, DR: B, LA: 100%" ] ] 13 => array:5 [ "identificador" => "tb0025" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "NSAIDs lead to an improvement in the quality of life of patients with chronic or acute rheumatic pathology.LE: 1+, DR: B, LA: 100%" ] ] 14 => array:5 [ "identificador" => "tb0030" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In all patients taking NSAIDs chronically CV risk estimation should be performed.LE: 2++, DR: B, LA: 89%CV risk estimation should be performed systematically in all patients who chronically used NSAIDs at least once a year.LE 4, DR: D, LA: 78%" ] ] 15 => array:5 [ "identificador" => "tb0035" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The administration of NSAIDs is associated with an increased risk of developing acute coronary syndrome (ACS) or other character atherothrombotic CV events (stroke and peripheral arterial problems).LE: 1++, DR: A, LA: 100%" ] ] 16 => array:5 [ "identificador" => "tb0040" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The increase in CV risk varies greatly depending on the type of NSAID used.LE: 1++, DR: A, LA: 100%Naproxen is one of the safest NSAID in terms of CV risk.LE: 1++, DR: A, LA: 100%Rofecoxib, diclofenac, indomethacin, etodolac etoricoxib and NSAIDs are the drugs most associated to CV risk.LE: 1+, DR B, LA: 100%" ] ] 17 => array:5 [ "identificador" => "tb0045" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The combination of anticoagulants (warfarin, coumarin derivatives, etc.) and NSAIDs should be avoided. If absolutely necessary, COXIB appear to be associated with a lower risk of bleeding complications.LE: 2+, DR: C, LA: 89%" ] ] 18 => array:5 [ "identificador" => "tb0050" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Avoid the use of NSAIDs, even in the short term, in patients with acute myocardial infarction taking ASA as it is associated with an increased CV risk.LE: 2+, DR: B, LA: 78%In patients taking low-dose aspirin, the association with ibuprofen and naproxen interferes with the antiplatelet effect of aspirin, so one should avoid using them together.LE: 1+, DR: C, LA: 100%" ] ] 19 => array:5 [ "identificador" => "tb0055" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients taking aspirin to prevent CV events requiring chronic treatment with NSAIDs, coxibs are a therapeutic option to consider.LE: 2+, DR: C, LA: 78%" ] ] 20 => array:5 [ "identificador" => "tb0060" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "A custom profile assessment baseline of the GI risk of each patient and NSAID use should be performed.LE 4, DR: D, LA: 100%" ] ] 21 => array:5 [ "identificador" => "tb0065" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Patients over 60 years of age constitute a risk factor by itself due to the occurrence of GI complications in patients taking NSAIDs, and this risk increases progressively with age.LE: 2++, DR: B, LA: 100%" ] ] 22 => array:5 [ "identificador" => "tb0070" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The presence of a history of complicated or uncomplicated gastroduodenal or peptic ulcer is a risk factor for the development of GI complications in patients taking NSAIDs.LE: 1+, DR: A, LA: 100%" ] ] 23 => array:5 [ "identificador" => "tb0075" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "It is not recommended to use 2 or more NSAIDs simultaneously, since concomitant use does not increase the effectiveness and it does increase toxicity.LE: 2+, DR: B, LA: 100%" ] ] 24 => array:5 [ "identificador" => "tb0080" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The risk of GI complications increases if high doses of NSAIDs are used in a sustained manner.LE: 2+, DR: B, LA: 100%The risk of GI complications is constant throughout the time that treatment with NSAID is maintained.LE: 2 -, DR: C, LA: 100%" ] ] 25 => array:5 [ "identificador" => "tb0085" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Co-administration of aspirin and acetaminophen do not appear to increase the gastroduodenal mucosal damage with respect to the use of aspirin alone so, if necessary, can be jointly employed in these circumstances.LE: 1−, DR: B, LA: 89%" ] ] 26 => array:5 [ "identificador" => "tb0090" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "NSAID use is associated with increased risk of injury and complications of the upper and lower GI tract.LE: 1+, DR: A, LA: 100%" ] ] 27 => array:5 [ "identificador" => "tb0095" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "H2 antagonist use for prevention of GI complications of NSAIDs is not recommended.LE: 1+, DR: A, LA: 100%" ] ] 28 => array:5 [ "identificador" => "tb0100" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "PPI associated with a nonselective NSAID is valid strategy for the prevention of high GI complications of NSAIDs in patients at risk.LE: 1++, DR: A, LA: 89%" ] ] 29 => array:5 [ "identificador" => "tb0105" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "Coxibs are superior to the combination of classical NSAIDs with a PPI in preventing injury of the GI tract.LE: 1+, DR: A, LA: 89%" ] ] 30 => array:5 [ "identificador" => "tb0110" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The use of a COXIB reduces complications in the upper and lower GI tract.LE: 1+, DR: A, LA: 100%" ] ] 31 => array:5 [ "identificador" => "tb0115" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The use of low dose aspirin increases 2–4 times the risk of GI complications, so patients with GI risk factors should be prescribed gastroprotection.LE: 1+, DR: A, LA: 89%" ] ] 32 => array:5 [ "identificador" => "tb0120" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients treated with NSAIDs, severe liver toxicity is rare, so no special monitoring measures are recommended.LE: 2++, DR: B, LA: 100%" ] ] 33 => array:5 [ "identificador" => "tb0125" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients with liver cirrhosis it is recommended to avoid the use of NSAIDs.LE: 2++, DR: B, LA: 100%" ] ] 34 => array:5 [ "identificador" => "tb0130" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "If treatment with NSAIDs is absolutely essential in patients with liver cirrhosis, using a COXIB is recommended for the shortest period of time possible.LE: 2+, DR: C, LA: 89%" ] ] 35 => array:5 [ "identificador" => "tb0135" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients with nonselective NSAID or coxib treatment-associated dyspepsia, a PPI is recommended as the drug of first choice.LE: 1++, DR: A, LA: 100%" ] ] 36 => array:5 [ "identificador" => "tb0140" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients suffering from inflammatory bowel disease (IBD), the use of NSAIDs should be avoided.LE: 1−, DR: B, LA: 89%In patients suffering from IBD and if it should be necessary to use NSAIDs in quiescent phases of the disease, the use of COXIBs is recommended at low doses for a short time.LE: 1−, DR: B, LA: 100%" ] ] 37 => array:5 [ "identificador" => "tb0145" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In chronic rheumatic patients receiving NSAIDs, renal function should be assessed by estimating glomerular filtration rate.LE: 2+, DR: C, LA: 89%In chronic rheumatic patients receiving NSAIDs, renal function should be assessed at least once a year.LE: 2+, DR: C, LA: 100%" ] ] 38 => array:5 [ "identificador" => "tb0150" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "In patients with chronic kidney disease stage 3 or renal comorbidity and/or associated CV, use of NSAIDs, except in special situations and with close clinical monitoring, is not recommended.LE: 2+, DR: C, LA: 100%In patients with chronic kidney disease stage 3 or renal comorbidity and/or associated CV, the use of higher doses than recommended of NSAIDs should be avoided, especially COXIB.LE: 2+, DR: C, LA: 89%In patients with chronic kidney disease stage 4 and 5 NSAID use is contraindicated.LE: 2+, DR: C, LA: 78%" ] ] 39 => array:5 [ "identificador" => "tb0155" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "The development of anemia or hemoglobin decreases>2g/dL is common in patients who take NSAIDs, even associated with PPI. Treatment with celecoxib was associated with a lower likelihood of developing this adverse effect.LE: 1+, DR: A, LA: 100%" ] ] 40 => array:5 [ "identificador" => "tb0160" "tipo" => "MULTIMEDIATEXTO" "mostrarFloat" => false "mostrarDisplay" => true "texto" => array:1 [ "textoCompleto" => "We recommend the use of paracetamol–NSAID combination in postoperative pain in the short term, provided there is no contraindication to the administration of the latter.LE: 1+, DR: A, LA: 78%One NSAID cannot be prioritized over another regarding their postoperative use.LE: 2++, DR: B, LA: 89%The combination in terms of dose and type of drug use in the postoperative period must be balanced empirically.LE: 3, DR: D, LA: 78%" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:158 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European Medicines Agency review concludes positive benefit-risk balance for non-selective NSAIDs" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ …3] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Estrategia clínica para la prevención de los efectos adversos sobre el tracto digestivo de los antiinflamatorios no esteroideos" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ …5] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical strategy to prevent the gastrointestinal adverse effects of nonsteroidal anti-inflammatory agents" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Appropriate use of non-steroidal anti-inflammatory drugs in rheumatology: guidelines from the Spanish Society of Rheumatology and the Mexican College of Rheumatology" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1699-258X(09)70197-4" "Revista" => array:6 [ …6] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SIGN Scottish Intercollegiate Guidelines Network" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ …3] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.38273.626655.63" "Revista" => array:5 [ …5] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medication guide for non-steroidal anti-inflammatory drugs (NSAIDs)" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ …3] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Approach to managing musculoskeletal pain: acetaminophen, cyclooxygenase-2 inhibitors, or traditional NSAIDs?" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ …6] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on guidelines for the treatment of chronic musculoskeletal pain" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-006-0203-8" "Revista" => array:7 [ …7] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of chronic musculoskeletal pain in the elderly: opinions on oral medication use" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10787-008-1623-7" "Revista" => array:6 [ …6] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of osteoarthritis with continuous versus intermittent celecoxib" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.110636" "Revista" => array:6 [ …6] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip" "autores" => array:1 [ …1] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2006.052308" "Revista" => array:6 [ …6] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies" "autores" => 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Original Article

Safe Prescription Recommendations for Non Steroidal Anti-inflammatory Drugs: Consensus Document Elaborated by Nominated Experts of Three Scientific Associations (SER-SEC-AEG)

Recomendaciones para una prescripción segura de antiinflamatorios no esteroideos: documento de consenso elaborado por expertos nominados por 3 sociedades científicas (SER-SEC-AEG)

Angel Lanasa,

Corresponding author

alanas@unizar.es

Corresponding author.

, Pere Benitob, Joaquín Alonsoc, Blanca Hernández-Cruzd, Gonzalo Barón-Esquiviase,#, Ángeles Perez-Aísaf, Xavier Calvetg, José Francisco García-Llorenteh, Milena Gobboi, José R. Gonzalez-Juanateyj

a Servicio de Aparato Digestivo, Hospital Clínico Lozano Blesa, Universidad de Zaragoza, IIS Aragón, CIBERehd, Zaragoza, Spain

b Servicio de Reumatología, Hospital del Mar, Universidad Autónoma de Barcelona, Barcelona, Spain

c Servicio de Cardiología, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid, Spain

d i+D+I, Unidad de Gestión Clínica de Reumatología, Servicio de Reumatología, Hospital Universitario Virgen Macarena, Sevilla, Spain

e Servicio de Cardiología, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain

f Unidad de Digestivo, Agencia Sanitaria Costa del Sol, Marbella, Málaga, Spain

g Servei de Digestiu, Hospital de Sabadell, Universidad Autónoma de Barcelona, CIBERehd, Sabadell, Barcelona, Spain

h Unidad de Reumatología, Hospital de Tortosa, Tortosa, Tarragona, Spain

i Unidad de Investigación, Sociedad Española de Reumatología, Madrid, Spain

j Servicio de Cardiología y Unidad Coronaria, Hospital Clínico Universitario, Santiago de Compostela, La Coruña, Spain

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In October 2006&#44; the Committee for Medicinal Products for Human Use of the EMEA issued a report<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> regarding the existence of new data on the risks of atherothrombotic CV type events related to traditional NSAIDs&#46; So it is currently considered that all NSAIDs&#44; in varying degrees&#44; are associated with increased GI and CV risk&#46; The increased CV risk due to the use of selective COX-2 is explained by an imbalance between inhibition of thromboxane and prostacyclin&#44; but given that the increased CV risk is also seen with nonselective classic NSAIDs&#44; the mechanism appears to be more complex&#46; Moreover&#44; both traditional and COX-2 NSAIDs are associated with an increase in blood pressure and edema&#44; to varying degrees&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2003&#44; the Spanish Gastroenterological Association &#40;ALA&#41; and the Spanish Society of Rheumatology &#40;SER&#41; contributed to the publication of a &#8220;clinical strategy for the prevention of adverse effects on the digestive tract by NSAIDs&#8221;&#44;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> and then&#44; a consensus document of the SER and the Mexican College of Rheumatology for the &#8220;Appropriate use of NSAIDs in rheumatology&#8221;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> was published in the year 2009&#46; The current review is a collaboration of ALA&#44; the SER and the Spanish Society of Cardiology &#40;SEC&#41;&#46; This review aims to promote a rational use of NSAIDs according to new studies published in recent years and help in an optimal decision-making process for the routine use of these drugs&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Operational Definitions of the Document</span><p id="par0025" class="elsevierStylePara elsevierViewall">The term NSAID in these recommendations refers to traditional NSAIDs as a group&#44; to selective COX-2 &#40;coxibs&#41; inhibitors and acetylsalicylic acid &#40;ASA&#41; at anti-inflammatory doses&#46; If a statement refers only to traditional NSAIDs&#44; coxibs or ASA&#44; this will be well specified in the recommendation&#46; We have not included other NSAID analgesics&#44; such as lysine clonixinate or metamizole&#46;</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Methodology</span><p id="par0030" class="elsevierStylePara elsevierViewall">The development of consensus was performed using a nominal group and the Delphi technique as shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Nominal Group</span><p id="par0035" class="elsevierStylePara elsevierViewall">Nine panelists &#40;three rheumatologists&#44; 3 gastroenterologists and 3 cardiologists&#41; from their respective scientific societies &#40;SER&#44; ALA and SEC&#41; and appointed by the boards of the same based on their experience and&#47;or publications on the topic in journals included in Medline&#44; formed the nominal group&#46; This group was coordinated by a methodologist of the Research Unit of the SER that established the scope&#44; users&#44; and paragraphs of consensus&#44; and the definitions used in the document&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">To carry out the group&#44; the panelists were provided with documents published previously on the subject&#44; and asked everyone to&#44; with no interaction among them&#44; develop their personal proposal following a scheme provided by the methodologist of the Research Unit of the SER&#44; who subsequently developed a joint document that included all proposals&#46; On 15 June 2012 the actual meeting where the background of the problem and the relevant methodological aspects were revised consensus took place&#46; Then&#44; the group worked on the entire document and tested each of the aspects to agree on &#40;user&#44; scope and topics to be included&#41;&#46; Each expert participant had the opportunity to vote on the appropriateness or otherwise of the inclusion of each of the proposed recommendations&#44; arguing the reasons for it&#46; Thus&#44; the options&#44; the final structure of the document and the heads of the sections hereof&#44; were successively rearranged&#46; Finally it was decided that the consensus would address primary care physicians&#44; rheumatologists&#44; cardiologists and gastroenterologists &#40;as users&#41;&#44; and would focus on issues of efficacy&#44; CV security and kidney safety &#40;range&#41;&#46; Those responsible for each of the paragraphs were distributed as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Drafting of Recommendations</span><p id="par0045" class="elsevierStylePara elsevierViewall">The recommendations were drafted by experts&#44; either individually or in working groups&#46; A common approach was established for its development&#44; so that each responsible manager should include a short&#44; synthetic statement of recommendation&#44; followed by its argumentative development&#44; supporting the recommendation with the best available evidence-based literature searches made for such a purpose by each panelist&#46; The level of evidence and strength of recommendation were established according to the SIGN<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> scale&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Delphi Survey</span><p id="par0050" class="elsevierStylePara elsevierViewall">To establish the degree of consensus&#44; a 2 round Delphi survey was conducted&#46; The recommendations submitted by the panelists were reformulated in the form of items to be answered using a Likert scale that measured the degree of agreement with the statement&#44; scoring it as 1 &#40;completely disagree&#41; to 5 &#40;completely agree&#41;&#46; Questionnaires were sent electronically via email to the panelists insuring that there was no interaction between them&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The first round was sent on January 28&#44; 2013 &#40;66 items grouped in 17 sections&#41;&#46; In the first round&#44; panelists were able to add new claims&#44; comments&#44; quotes or arguments for each item when&#44; from their point of view&#44; they were important aspects that should be included in the consensus document&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">It was felt that there was agreement with the item when the average score was equal to or greater than 4&#44; and disagreement when the score was less than or equal to 2&#46; In both cases &#40;agreement and disagreement&#41; there is consensus&#46; In the rest of the possibilities&#44; it was considered that the item was problematic and no consensus could be established&#46; Based on the comments of the panelists the wording of some items was modified&#44; others were broken up and a list of possible new recommendations to be included in the questionnaire for the second round was added&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The second round was sent on February 11&#44; 2013 &#40;73 items grouped in 17 sections&#41;&#46; Analysis of the second round was performed using the same methodology and the same criteria were used as in the first &#40;agreement or disagreement and conflicting items&#41;&#46; It was felt that there was a consensus when more than 75&#37; of the panelists agreed with the statement &#40;agreement score &#8805;4&#41;&#46; The remaining cases &#40;conflicting items&#41; are considered recommendations without consensus&#44; and are not included herein&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Recommendations</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Efficacy</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Directions</span><p id="par0070" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0005"></elsevierMultimedia></p><p id="par0085" class="elsevierStylePara elsevierViewall">The approved indications for NSAID on the insert are varied&#44; according to the type of pain ranging from those originated in the musculoskeletal or neurological system to dysmenorrhea&#46; This makes the target population very broad and heterogeneous&#46; NSAID responses vary among individuals&#44; which obliges the individualization of the indication and evaluation of such a response to these drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a><elsevierMultimedia ident="tb0010"></elsevierMultimedia></p><p id="par0100" class="elsevierStylePara elsevierViewall">One cannot recommend any NSAID over another based on their clinical response&#46; Several publications provide sufficient evidence to assert that efficacy is similar&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Time of Use</span><p id="par0105" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0015"></elsevierMultimedia></p><p id="par0130" class="elsevierStylePara elsevierViewall">To control pain&#44; NSAIDs share indications with other pharmacological and non-pharmacological interventions&#46; NSAIDs should be used for the shortest duration and the lowest possible dose&#44; adapting their use to different approved indications&#46; This recommendation is collected by regulatory agencies&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;8</span></a> based on data showing dose-dependent adverse effects and that the risk is maintained over time&#46; Therefore&#44; given the potential for adverse effects&#44; its use is recommended when the alternatives are not possible&#44; both for intolerance as for ineffectiveness&#46;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In osteoarthritis&#44; NSAIDs continuous treatment is most effective in controlling the symptoms than on-demand use&#46; Nevertheless&#44; the latter is often recommended because of possible undesirable side effects&#44; as stated in a study lasting 22 weeks for the prevention of outbreaks of osteoarthritis of the knee and hip&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In another prospective multicenter randomized trial of 24 weeks in patients with hip or knee osteoarthritis&#44; the frequency of adverse effects was similar in those taking celecoxib continuously compared to those taking it intermittently depending on the symptoms of<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> the patients&#46; In psoriatic arthritis&#44; due to the intestinal and CV specific risks of these patients&#44; NSAIDs are recommended at the lowest dose and for the shortest time possible due to their potential toxicity&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a><elsevierMultimedia ident="tb0020"></elsevierMultimedia></p><p id="par0150" class="elsevierStylePara elsevierViewall">In ankylosing spondylitis NSAIDs are recommended as first-line therapy if patients present with inflammatory back pain and stiffness&#44; being continued as treatment of choice if the disease is active and persistently symptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#8211;18</span></a> NSAIDs improve function and decrease disease activity in ankylosing spondylitis&#44; while disease-modifying drugs have no effect on these parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> There has also been a reduction in the degree of radiographic progression in patients who take NSAIDs continuously associated with anti-TNF drugs&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> Similarly&#44; continued treatment with celecoxib is associated with a lower radiographic progression compared with on demand use&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> The <span class="elsevierStyleItalic">German Early Spondyloarthritis Inception Cohort</span> notes that patients with ankylosing spondylitis associated with a high rate of NSAID use for more than 2 years have a slowing of new spinal bone formation compared to the those that have a low rate&#46; This apparent protective effect is exclusive of those patients with high C-reactive protein in time and the presence of syndesmophytes at onset&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Patients with elevated acute phase reactants benefit more from continuous treatment with NSAIDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#8211;25</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Quality of Life</span><p id="par0155" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0025"></elsevierMultimedia></p><p id="par0170" class="elsevierStylePara elsevierViewall">The efficacy of NSAIDs in reducing pain and symptoms associated with inflammation in patients with acute or chronic rheumatic disease is unquestionable&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> These benefits produced significant improvement in the physical function subdomain and in the quality of life of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#8211;30</span></a> This improvement occurred more frequently in patients with a worse baseline physical function&#44; fewer comorbidities and shorter duration of symptoms&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Retention rates &#40;days of treatment without abandonment&#41; of NSAIDs&#44; especially COXIB remain high&#44; particularly in chronically ill and patients over 65 years&#46; The average duration of treatment in rheumatic patients for celecoxib&#44; rofecoxib&#44; naproxen and ibuprofen was 15&#44; 13&#44; 10 and 10<span class="elsevierStyleHsp" style=""></span>months&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Differences in safety&#44; especially GI&#44; could have significant implications for the quality of life of patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;32</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Cardiovascular Risk</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Stratification of Vascular Risk</span><p id="par0180" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0030"></elsevierMultimedia></p><p id="par0205" class="elsevierStylePara elsevierViewall">Given the CV risk associated with NSAID therapy&#44; it is important to evaluate this parameter when prescribing it and choosing it as an appropriate treatment&#46; The Third Joint <span class="elsevierStyleItalic">Task Force</span> on Cardiovascular Disease Prevention in Clinical Practice recommended a <span class="elsevierStyleItalic">Systematic Coronary Risk Evaluation</span> &#40;SCORE&#41; model for CV risk estimation in Europe&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> which is based on studies on European population&#46; Given the geographic variability of CV risk in Europe&#44; 2 SCORE models have been developed&#44; for countries with high or low risk&#44; setting Spain in the low incidence zone&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">34&#44;35</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The CV risk is stratified into very high&#44; high&#44; moderate or low CV risk<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;37</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; This new classification of CV risk levels is directly related to the achievement of therapeutic goals over increasingly stringent classic CV risk factors&#46; Thus&#44; specifically defined lipid goals are 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in plasma LDL-cholesterol levels for patients at very high CV risk 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL for high-risk patients and 115<span class="elsevierStyleHsp" style=""></span>hp mg&#47;dL in patients with moderate CV risk&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">The first &#8220;<span class="elsevierStyleItalic">EULAR Standing Committee for International Clinical Studies Including Therapeutics</span>&#8221; <span class="elsevierStyleItalic">consensus</span> for CV risk management in patients with rheumatoid arthritis and other inflammatory arthritis &#40;spondyloarthropathy&#41; was published in 2010&#46; These diseases&#44; in particular rheumatoid arthritis&#44; have been linked directly to an increased cardiovascular risk and long-term cardiovascular mortality&#46; This consensus recommends evaluating CV risk through the modified SCORE chart &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; and proposes a Decalogue of recommendations based on scientific evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> In the general aspects of estimation and CV risk management&#44; these recommendations could also be extended to patients with osteoarthritis&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Cardiovascular Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs</span><p id="par0220" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0035"></elsevierMultimedia></p><p id="par0235" class="elsevierStylePara elsevierViewall">In the absence of treatment&#44; administration of NSAIDs increases the risk of ACS or other CV atherothrombotic problems&#46; The clinical trials that determined the association between NSAIDs and CV events were not specifically designed for this purpose&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;40</span></a> Observational studies and meta-analyses of observational and clinical trials indicate that all NSAIDs increase the CV risk although to varying and&#44; in general&#44; low degrees&#46; A recently conducted review by the Spanish Agency for Medicines and Health Products &#40;AEMPS&#41; and the Committee for Medicinal Products for Human Use &#40;CHMP&#41; of the European Medicines Agency &#40;EMA&#41;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> has concluded that recent evidence confirms previous findings published in 2006&#44; which showed an increased CV risk of atherothrombotic type for NSAIDs&#44; although the risk&#47;benefit balance remains positive&#46;<elsevierMultimedia ident="tb0040"></elsevierMultimedia></p><p id="par0270" class="elsevierStylePara elsevierViewall">Different meta-analyses have indicated to a greater or lesser extent that all NSAIDs studied increased CV risk&#44; although the absolute magnitude is limited&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42&#44;43</span></a> A meta-analysis of observational studies published by McGettigan and Henry<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> in populations with high CV risk studied the most currently used NSAIDS &#40;naproxen&#44; ibuprofen&#44; celecoxib&#44; diclofenac&#44; indomethacin&#44; piroxicam&#44; meloxicam&#44; etodolac&#44; etoricoxib and valdecoxib&#41;&#46; The overall conclusions of the review suggested that naproxen and low doses of ibuprofen are associated with smaller increases in CV risk&#46; Diclofenac clearly increased CV risk&#46; The data for etoricoxib are sparse&#44; but comparisons with naproxen and ibuprofen showed a higher CV risk&#46; Indomethacin was also associated with a significant increase in CV risk&#46; In the MEDAL study&#44; etoricoxib was associated to a CV risk equal to that of diclofenac&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">The most recent large meta-analysis of clinical trials with individual patient data indicates that NSAIDs and coxibs have increased CV risk compared to placebo&#44; with no significant differences between them globally&#46; Among the nonselective NSAIDs&#44; CV risk was higher with diclofenac&#44; which presented a similar risk to that of coxibs&#46; Naproxen meanwhile&#44; at doses of 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; was not associated with increased CV risk&#44; unlike ibuprofen and diclofenac&#44; the only nonselective NSAIDs most studied&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> There is also a clear association between the risk of developing heart failure and the administration of these drugs<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> in addition to the well-known relationship of NSAIDs and the development of episodes or exacerbations of heart failure&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Patients with ischemic heart disease have a higher risk of CV events when given NSAIDs&#46; A Spanish<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> case&#8211;control study&#44; which included 6000 participants concluded that NSAID use is associated with an overall increase of 16&#37; in coronary risk &#40;OR&#58; 1&#46;16&#44; 95&#37; CI&#58; 0&#46;95&#8211;1&#46;42&#41;&#46; The use of high doses increased it by 64&#37; &#40;OR&#58; 1&#46;64&#44; 95&#37; CI&#58; 1&#46;06&#8211;2&#46;53&#41; compared to those taking low doses&#46; In patients with ischemic heart disease&#44; the increased risk was 84&#37; &#40;OR&#58; 1&#46;84&#44; 95&#37; CI&#58; 1&#46;13&#8211;3&#46;00&#41;&#46; The meta-analysis of<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> McGettigan and Henry also supports the fact that high doses are associated with increased risk&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Anticoagulant Use</span><p id="par0285" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0045"></elsevierMultimedia></p><p id="par0300" class="elsevierStylePara elsevierViewall">Evidence through observational studies showing an increased risk of upper gastrointestinal bleeding in patients using NSAIDs and anticoagulants is extensive&#46; In general&#44; NSAIDs should be avoided in patients using these drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">48&#8211;51</span></a> The safety of novel anticoagulants such as dabigatran&#44; rivaroxaban and apixaban associated with NSAIDs does not seem different from the classical anticoagulants&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Interactions with anticoagulants are different for different NSAIDs&#46; Aspirin&#44; phenylbutazone and mefenamic acid very significantly enhance the anticoagulant effect of warfarin&#44; displacing albumin and decreasing its metabolism in the liver&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> Tenoxicam&#44; meloxicam&#44; lornoxicam&#44; nimesulide&#44; etodolac&#44; nabumetone and celecoxib did not significantly increase the <span class="elsevierStyleItalic">international normalized ratio</span> &#40;INR&#41; in anticoagulated individuals&#46; Conversely&#44; diclofenac&#44; ibuprofen and naproxen increased bleeding time&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">54&#8211;56</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">A study that evaluated 98&#44;821 elderly patients on continuous treatment with warfarin indicated that the risk of upper gastrointestinal bleeding associated with NSAIDs or coxibs was similar&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> However&#44; more recent studies have indicated that celecoxib combined with warfarin was associated with lower risk of GI bleeding hospitalizations than the association of warfarin with ibuprofen&#44; indomethacin&#44; etodolac&#44; nabumetone and naproxen&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">58&#44;59</span></a> All this means that&#44; even with reservations&#44; COXIBs should be considered as a first choice in situations where an NSAID is needed and the problem cannot be handled using other therapies&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Use of Antiplatelet Agents</span><p id="par0315" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0050"></elsevierMultimedia></p><p id="par0340" class="elsevierStylePara elsevierViewall">Ibuprofen&#44; naproxen and indomethacin&#44; but not paracetamol&#44; diclofenac or coxibs&#44; interfere with aspirins ability to irreversibly acetylate the platelet COX-1 enzyme&#44; so it is likely that these drugs reduce the protective effect of aspirin on the risk of atherosclerotic events&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#8211;62</span></a></p><p id="par0345" class="elsevierStylePara elsevierViewall">The evidence is not yet sufficient to make firm recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">63</span></a> However&#44; ibuprofen should not be taken until at least 1<span class="elsevierStyleHsp" style=""></span>h after ingestion of aspirin&#46; For patients taking enteric coated-ASA &#40;mostly in Spain&#41; the problem is greater because the peak maximum release is late &#40;beyond 4<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; which makes interaction with ibuprofen is very likely&#46; Thus&#44; a study showed that the antiplatelet effect of low dose enteric coated aspirin is attenuated when ibuprofen is administered 2&#44; 7 and 12<span class="elsevierStyleHsp" style=""></span>h after ASA&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">64&#44;65</span></a> In the case of naproxen&#44; interaction was lower when administered at least 2<span class="elsevierStyleHsp" style=""></span>h after ASA&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> There is controversy about the extent to which this interaction may have clinical impact in terms of CV mortality in patients taking aspirin and ibuprofen&#44; as the 2 studies are contradictory&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67&#44;68</span></a><elsevierMultimedia ident="tb0055"></elsevierMultimedia></p><p id="par0360" class="elsevierStylePara elsevierViewall">Celecoxib&#44; rofecoxib&#44; and lumiracoxib do not interfere with ASA in its ability to irreversibly acetylate platelet COX-1&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#44;69</span></a> Of these&#44; only celecoxib is available in the market&#44; which reduces the options&#44; as there are no data for etoricoxib&#46; The trouble with using ASA and COXIB is determined by the CV risk associated with them and the fact that the EMA&#44; but not the FDA&#44; established a contraindication to the use of coxibs in patients with previous history of CV events&#46; This limits considerably the treatment options in this population&#44; given also that naproxen&#44; although neutral from the point of view CV risk at doses of 500<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; is associated with increased GI risk and may interfere with ASA&#46; So&#44; in patients with ASA who have not presented a CV event&#44; celecoxib at low doses and for the shortest possible time is a reasonable therapeutic option based on epidemiological studies indicating that the drug has no greater risk than other traditional NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Prescribing recommendations according to CV and GI risk are developed in the algorithm of the attached as <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Gastrointestinal Risk</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Digestive Risk Stratification</span><p id="par0365" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0060"></elsevierMultimedia></p><p id="par0380" class="elsevierStylePara elsevierViewall">The keys for this custom evaluation are those outlined in this section&#46; The risk profile is established for each patient according to <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> and will be the one to guide prevention strategy&#46;<elsevierMultimedia ident="tb0065"></elsevierMultimedia></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0395" class="elsevierStylePara elsevierViewall">As age increases&#44; the risk of developing GI complications in patients taking NSAIDs also increases progressively&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">70&#44;71</span></a> Patients over 60 years of age alone is a risk factor for the occurrence of GI complications&#44; and this risk is increased in patients receiving NSAIDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">72&#44;73</span></a> It is estimated that approximately 6 upper GI complications occur per 1000 persons&#47;year in patients taking NSAIDs and with an age between 60 and 69<span class="elsevierStyleHsp" style=""></span>years&#46; This estimate increases to 16 per 1000<span class="elsevierStyleHsp" style=""></span>persons&#47;year in patients aged between 70 and 79 years&#46;<elsevierMultimedia ident="tb0070"></elsevierMultimedia></p><p id="par0410" class="elsevierStylePara elsevierViewall">The existence of a previous history of uncomplicated gastric or duodenal ulcer or a history of GI bleeding or perforation is an independent risk factor for the development of peptic ulcer complications associated with taking NSAIDs&#46; This finding has been confirmed in most observational studies and clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51&#44;71&#44;74&#8211;79</span></a><elsevierMultimedia ident="tb0075"></elsevierMultimedia></p><p id="par0425" class="elsevierStylePara elsevierViewall">The combination of 2 or more NSAIDs increases the risk of bleeding over the individual risk for each individual NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> Similarly&#44; and possibly linked to this same phenomenon&#44; it has been noted that the change of an NSAID to another during an episode also increases the risk of upper GI bleeding&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">81</span></a></p><p id="par0430" class="elsevierStylePara elsevierViewall">This increased risk with the combination of 2 NSAIDs is also observed with the combination of a classic NSAIDs or coxibs with aspirin at low doses used for preventing CV events&#44; currently the most commonly used combination&#46; In the CLASS study<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> patients who received a classic NSAID plus low-dose ASA had an annualized complication rate of 2&#46;1&#37;&#44; higher than that seen in patients receiving NSAIDs alone &#40;1&#46;2&#37;&#41;&#46; A number of observational studies have shown that the combination of NSAIDs or coxibs with aspirin increases the risk of upper gastrointestinal bleeding over the risk estimates for each of the drugs individually&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">81&#44;83&#44;84</span></a> Post hoc analysis comparisons of nonrandomized and observational studies have suggested that the risk associated with traditional NSAID combination&#43;ASA is possibly greater than that associated with COXIB&#43;ASA&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">85&#44;86</span></a></p><p id="par0435" class="elsevierStylePara elsevierViewall">Finally&#44; the concomitant use of steroids has been included in some previous reviews among arisk factors for GI complications&#46; However&#44; the latest evidence shows that the incidence of complications is very low&#44; so it cannot be established that this combination of drugs constitutes an essential GI risk factor of&#46;<a class="elsevierStyleCrossRefs" href="#bib0435"><span class="elsevierStyleSup">87&#44;88</span></a><elsevierMultimedia ident="tb0080"></elsevierMultimedia></p><p id="par0460" class="elsevierStylePara elsevierViewall">High GI risk complication in patients treated with NSAIDs is dose dependent&#46; While it has been suggested that the risk of developing high GI complications is higher during the first month of treatment and then stays stable during the remaining period of treatment&#44; long-term clinical trials indicate that the risk of developing complications is stable throughout time&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">89</span></a><elsevierMultimedia ident="tb0085"></elsevierMultimedia></p><p id="par0475" class="elsevierStylePara elsevierViewall">A study in patients with prior acute myocardial infarction noted that short-term treatment with most NSAIDs is associated with an increased CV risk&#46; Diclofenac was associated with an increased CV risk from the onset of treatment to its end&#46; Ibuprofen also showed an increased risk when used for more than a week&#46; Celecoxib was associated with increased risk of death after a treatment duration of 14&#8211;30<span class="elsevierStyleHsp" style=""></span>days&#46; Naproxen was the only NSAID evaluated that was not associated with an increased risk of heart attack or death&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">90</span></a></p><p id="par0480" class="elsevierStylePara elsevierViewall">There is no strong evidence that the use of acetaminophen is associated with increased cardiovascular risk&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">91</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Gastrointestinal Complications Associated With the Use of NSAIDs</span><p id="par0485" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0090"></elsevierMultimedia></p><p id="par0500" class="elsevierStylePara elsevierViewall">NSAID treatment is associated with serious adverse events which affect the upper and lower gastrointestinal tract&#46; They can occur as uncomplicated symptomatic ulcers or upper gastrointestinal bleeding&#44; lower GI bleeding and GI perforation&#46; These side effects occur in the 1&#37;&#8211;4&#37; of patients treated with NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">82</span></a> The relative risk for developing serious upper GI complications in patients treated with NSAIDs has been estimated between 3 and 5 times compared to those untreated&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">92</span></a></p><p id="par0505" class="elsevierStylePara elsevierViewall">The incidence of serious complications of the lower digestive tract is not well defined&#44; but it could account for 20&#37; of the morbidity associated with NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">93</span></a> Studies show that 70&#37; of patients taking NSAIDs chronically develop lesions of the lower GI tract&#44; although many of them have little clinical relevance&#46; Among the lesions described&#44; increased intestinal permeability&#44; inflammation&#44; erosions&#44; ulcers&#44; strictures&#44; anemia&#44; protein losing enteropathy&#44; diverticulitis&#44; bleeding and perforation are included&#46; Recent data on the rate of upper and lower GI perforation in patients with rheumatoid arthritis show that 83&#37; occur in the lower tract&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">94</span></a> Additionally&#44; some patients with certain rheumatic of inflammatory diseases also have associated inflammatory bowel disease&#44; often subclinical&#44; that possibly&#44; but not exclusively be due to chronic NSAID use&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Prevention Strategies</span><p id="par0510" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0095"></elsevierMultimedia></p><p id="par0525" class="elsevierStylePara elsevierViewall">H2 antagonists have been shown to be inferior to proton pump inhibitors &#40;PPI&#41;&#44; in both healing and prevention of ulcers associated with NSAID or ASA use&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">95&#8211;99</span></a><elsevierMultimedia ident="tb0100"></elsevierMultimedia></p><p id="par0540" class="elsevierStylePara elsevierViewall">PPIs have been shown to be superior to H2 antagonists for the prevention of NSAID-induced endoscopic ulcers and similar to misoprostol&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">100&#44;101</span></a> but better tolerated&#46; Observational studies and clinical trials have suggested that PPIs reduce the risk of GI complications in patients taking NSAIDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;53&#44;71&#44;76</span></a><elsevierMultimedia ident="tb0105"></elsevierMultimedia></p><p id="par0555" class="elsevierStylePara elsevierViewall">Coxibs have been proven superior to the combination of NSAID plus placebo and as effective as the use of nonselective NSAID associated to PPIs for the prevention of GI lesions and<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">69&#44;82&#44;102&#8211;105</span></a> complications&#46; Data from randomized trials indicate that coxibs are associated with a lower frequency of low GI lesions produced by the association of a nonselective NSAID plus PPI&#46;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">103&#44;106&#44;107</span></a><elsevierMultimedia ident="tb0110"></elsevierMultimedia></p><p id="par0570" class="elsevierStylePara elsevierViewall">These drugs have been developed with the intent of reducing GI toxicity associated with NSAID use&#46; Several meta-analyses have indicated that the risk of upper GI complications with COXIB was 50&#37; less than the risk seen with conventional NSAIDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">85&#44;108</span></a></p><p id="par0575" class="elsevierStylePara elsevierViewall">The CONDOR and GI REASON studies&#44; meanwhile&#44; have shown that celecoxib was associated with a lower frequency and a reduction in all clinically significant episodes of GI tract toxicity when compared to PPI and associated diclofenac &#40;CONDOR&#41; or traditional NSAIDs associated or not to PPI &#40;GI REASON&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">107&#44;109</span></a> One study showed a lower &#40;not significant&#41; rate of complications with etoricoxib versus diclofenac&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">110</span></a> The MEDAL study indicates in turn that etoricoxib was not superior to diclofenac regarding the incidence of upper and lower GI complications&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">110</span></a><elsevierMultimedia ident="tb0115"></elsevierMultimedia></p><p id="par0590" class="elsevierStylePara elsevierViewall">Antiplatelet doses of aspirin doubles the risk of GI bleeding and hospitalization compared to people who do not use it&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">92</span></a> This causes different clinical situations in patients with CV and GI risk&#44; and doubts may arise between maintaining or interrupting treatment with ASA&#46; Such disruption can precipitate serious CV effects&#44; including death&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">111&#44;112</span></a></p><p id="par0595" class="elsevierStylePara elsevierViewall">ASA therapy is associated with the development of peptic ulcers&#44; including esophageal&#44; gastroesophageal reflux disease &#40;GERD&#41; or dyspepsia&#44; besides upper GI complications&#46; Therefore&#44; the benefits of treatment with PPIs in patients taking ASA also extend to a better control of symptoms and lesions associated with GERD&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">113</span></a></p><p id="par0600" class="elsevierStylePara elsevierViewall">Recent data indicate that the combined use of PPI&#44; low dose aspirin and clopidogrel in patients with CV risk is associated with a low frequency of GI bleeding &#40;1&#46;8 cases per 100 patient-years&#41;&#46; However&#44; a shift in the location thereof to the lower GI tract is observed since&#44; for all bleeding episodes&#44; 73&#37; were found in the small intestine and in the colon &#40;many of them as a result of vascular injury&#44; possibly preexisting&#41;&#46; These hemorrhages occurred predominantly at an early stage during the first year of follow up&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">114</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Liver Risk</span><p id="par0605" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0120"></elsevierMultimedia></p><p id="par0620" class="elsevierStylePara elsevierViewall">Several systematic reviews assessing patients in clinical trials show a very low incidence of serious hepatic effects associated with NSAID use&#46; A systematic review including 132 studies shows that the need to discontinue NSAID due to adverse effects was not significantly higher than the placebo group&#44; except for diclofenac&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">115</span></a> Another analysis that brings together 41 studies showed the incidence of hepatic adverse effects of celecoxib to be 1&#46;1&#37;&#44; 4&#46;2&#37; for diclofenac&#44; 1&#46;5&#37; for ibuprofen and 0&#46;9&#37; for placebo<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">116</span></a>&#59; the rate of serious hepatic adverse events was 5&#47;100<span class="elsevierStyleHsp" style=""></span>000 for celecoxib and 21&#47;100<span class="elsevierStyleHsp" style=""></span>000 for diclofenac&#46; The need for hospitalization due to toxicity has been estimated at between 3 and 23 per 100<span class="elsevierStyleHsp" style=""></span>000 patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">117&#44;118</span></a> Transient elevations of transaminases are common&#44; and in most cases do not progress&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">115</span></a> Although cases of toxic hepatitis&#44; and even cases of severe hepatitis and death have been described due to NSAID&#44;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">115&#44;119&#8211;122</span></a> these are exceptional&#44; and there is no monitoring system to determine which patients will have a serious adverse liver reaction&#44; so monitoring measures are not recommended&#46; The risk of liver toxicity is significantly increased with diclofenac than with other NSAIDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0575"><span class="elsevierStyleSup">115&#44;116</span></a><elsevierMultimedia ident="tb0125"></elsevierMultimedia></p><p id="par0635" class="elsevierStylePara elsevierViewall">The use of NSAIDs in patients with cirrhosis has been linked to the onset of variceal bleeding&#44;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">123</span></a> and it is well known for his ability to impair renal function in patients with both compensated and decompensated liver cirrhosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">124&#44;125</span></a> For these reasons NSAIDs are considered contraindicated in patients with chronic liver disease and cirrhosis&#46;<elsevierMultimedia ident="tb0130"></elsevierMultimedia></p><p id="par0650" class="elsevierStylePara elsevierViewall">A study in 28 patients with cirrhosis and ascites assessed for 3 days the effect of celecoxib 200<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h&#44; naproxen 500<span class="elsevierStyleHsp" style=""></span>mg every 12<span class="elsevierStyleHsp" style=""></span>h placebo on renal function and platelet aggregation&#46; Neither celecoxib nor placebo induced changes in renal or platelet function&#46; In contrast&#44; naproxen induced a marked reduction in glomerular filtration&#44; renal plasma flow and urine output&#44; along with a significant antiplatelet effect&#46;<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">126</span></a> On the other hand&#44; Agrawal et al&#46; noted that etoricoxib<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">127</span></a> was well tolerated in patients with moderate or severe hepatic impairment&#46; However&#44; given the limited experience&#44; it is also recommended to avoid the use of coxibs in patients with liver disease&#44; and especially if presenting decompensated liver cirrhosis&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Dyspepsia</span><p id="par0655" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0135"></elsevierMultimedia></p><p id="par0670" class="elsevierStylePara elsevierViewall">It is estimated that between 10&#37; and 30&#37; of patients receiving NSAIDs have dyspepsia&#44; and dyspepsia leads to discontinuation of treatment in 5&#37;&#8211;15&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">128</span></a> The addition of a PPI versus placebo was associated with a lower frequency of dyspepsia in<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">101</span></a> patients treated with NSAIDs&#46; A meta-analysis by Spiegel et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">129</span></a> evaluated 26 studies comparing a COXIB vs traditional NSAIDs or traditional NSAID plus PPI vs NSAIDs alone&#46; Comparing COXIB vs traditional NSAIDs showed a relative risk reduction of symptoms of 12&#37; and an absolute reduction of 3&#46;7&#37;&#46; Comparison of traditional NSAIDs &#123;3&#43;&#125; PPI vs traditional NSAIDs showed a relative risk reduction of 66&#37; and an absolute risk reduction of 9&#37;&#46; The number needed to treat to prevent dyspepsia was 27 for coxibs and 11 for traditional NSAIDs plus PPI&#46; These results should be evaluated carefully&#44; since a direct comparison between coxibs and traditional NSAIDs&#43;PPI was not made&#46; In an ad hoc systematic search performed&#44; 6 studies directly comparing with a traditional NSAID COXIB&#43;PPI were found&#46;<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">102&#44;103&#44;106&#44;130&#8211;132</span></a> The meta-analysis of 6 studies with data on dyspepsia suggests&#44; however&#44; that this effect is true&#46; Dyspepsia incidence was 11&#46;8&#37; &#40;112&#47;947&#41; in those receiving one COXIB vs 7&#46;4&#37; &#40;72&#47;977&#41; in patients treated with a traditional or nonselective NSAIDs&#43;PPI &#40;OR&#58; 2&#46;2&#44; 95&#37; CI&#58; 1&#46;3&#8211;3&#46;6&#41;&#46; Given the high efficacy of PPIs in the treatment of dyspepsia associated with NSAIDs&#44; it seems reasonable to recommend their use in the case of patients having dyspepsia associated with the use of coxibs&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Inflammatory Bowel Disease</span><p id="par0675" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0140"></elsevierMultimedia></p><p id="par0700" class="elsevierStylePara elsevierViewall">It is estimated that up to one-third of patients with IBD develop arthritis which may or may not be linked<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">133</span></a> pathogenically with the disease&#46; This implies that many patients with IBD require some type of NSAID at any given point in their evolution&#46; Existing epidemiological studies are generally of poor quality and results clearly contradictory&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">134&#8211;136</span></a> Moreover&#44; there are no clinical trials to show that taking NSAIDs produce worsening or recurrence of IBD&#44; although there are case series with varying numbers of patients that do suggest it&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">134</span></a> In this sense&#44; a relatively recent study indicated that 17&#37;&#8211;28&#37; of patients in remission with Crohn&#39;s disease or ulcerative colitis who received nonselective NSAIDs such as naproxen&#44; diclofenac&#44; indomethacin or nabumetone for 4 weeks&#44; had recurrence in the first 9<span class="elsevierStyleHsp" style=""></span>days after taking the drug&#46; This did not occur in those taking nimesulide &#40;selective inhibitor of COX-2&#41;&#44; low-dose aspirin or paracetamol&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">137</span></a> Few clinical trials have tested whether the use of selective COX-2 inhibitors is associated with quiescent IBD relapses&#46; A double-blind randomized trial compared etoricoxib &#40;60&#8211;120<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; versus placebo over a period of 3<span class="elsevierStyleHsp" style=""></span>months in patients with Crohn&#39;s disease or ulcerative colitis&#46; The recurrence rate was 10&#37; in both situations&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">138</span></a> In another similar trial&#44; but with a shorter observation period of 14 days celecoxib 200<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h was compared to placebo in patients with ulcerative colitis&#44; with the same recurrence rates below 3&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">139</span></a></p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Renal Risk</span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Renal Risk Stratification</span><p id="par0705" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0145"></elsevierMultimedia></p><p id="par0730" class="elsevierStylePara elsevierViewall">NSAIDs interfere with renal homeostasis&#46; This has implications for renal function&#44; known in classic NSAIDs&#44; which as a result of the most recent investigations have been better defined in COXIBs&#46; Systematic reviews of the risk of developing renal comorbidity in rheumatic patients have difficulty concluding on the magnitude of the problem&#44; because clinical trials do not measure systematically renal outcomes or as part of the primary events of interest&#46;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">140&#8211;142</span></a></p><p id="par0735" class="elsevierStylePara elsevierViewall">The Spanish Society of Nephrology recommended an annual estimate of renal function by glomerular filtration&#46; Accordingly&#44; the presence of chronic renal disease is categorized according to <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">143</span></a> A moderate risk of developing renal adverse event is present if patients have chronic kidney disease stage 3 and&#47;or intravascular volume depletion&#44; hypertension or congestive heart failure and peripheral edema is&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0740" class="elsevierStylePara elsevierViewall">Stages 4 and 5 are considered at high risk of developing renal adverse event&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Renal Complications Associated With the Use of Nonsteroidal Anti-inflammatory Drugs</span><p id="par0745" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0150"></elsevierMultimedia></p><p id="par0780" class="elsevierStylePara elsevierViewall">NSAIDs lead to a decreased renal function and sodium and water retention&#46; Clinically&#44; this may present as elevated serum creatinine&#44; edema&#44; hypertension&#44; water and electrolyte imbalance&#44; renal failure&#44; renal papillary necrosis or nephrotic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">140</span></a> The relative risk of renal adverse event is different for each type of NSAID&#44; and apparently there is no class effect&#46; As with other toxic effects&#44; these are dose dependent and accumulate over time&#46; Moreover&#44; in rheumatic patients renal and CV comorbidities are often associated&#44; which increases the risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">140&#44;141&#44;144</span></a></p><p id="par0785" class="elsevierStylePara elsevierViewall">Decreased renal function &#40;elevated serum creatinine&#62;1&#46;3 times the upper normal limit&#41; occurs with a frequency of 1&#37;&#46; This elevation was observed equally in patients receiving therapeutic doses of NSAIDs&#44; and is higher with NSAIDs than placebo&#46;</p><p id="par0790" class="elsevierStylePara elsevierViewall">Another clinically relevant side effect associated with NSAIDs is the development of peripheral edema&#44; with an estimated risk of 3&#37;&#46; This risk is even greater when COXIBs are used than with placebo &#40;5&#37;&#8211;38&#37; higher in clinical trials in which edema is a major variable in the research&#41;&#46; However&#44; celecoxib at doses of 200<span class="elsevierStyleHsp" style=""></span>mg&#47;day was not associated with increased risk of edema&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">145</span></a> This suggests that the presence of edema does not follow a specific effect of the coxib class&#46; The development of heart failure due to the retention of sodium and water in susceptible patients is another common side effect of all NSAIDs&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">70</span></a></p><p id="par0795" class="elsevierStylePara elsevierViewall">All NSAIDs are associated with increased blood pressure in hypertensive subjects&#44; and this has little effect in individuals with normal blood pressure&#46; In general&#44; the frequency of hypertension associated with NSAIDs is &#8776;2&#37; and occurs more frequently in subjects with renal comorbidity and&#47;or pre-existing CV disease&#46; The minimum mean change in blood pressure after initiation of NSAID is an elevation of 5<span class="elsevierStyleHsp" style=""></span>mmHg but the clinical significance of this increase is uncertain&#46; The risk is higher for coxibs &#40;rofecoxib&#62;etoricoxib and lower for celecoxib&#41;&#46; It is important to monitor blood pressure after initiation of NSAID&#44; especially in the elderly&#44; in patients with pre-hypertension and in patients with chronic renal disease&#46; The use of NSAIDs is contraindicated in patients with uncontrolled hypertension&#46;<a class="elsevierStyleCrossRefs" href="#bib0730"><span class="elsevierStyleSup">146&#8211;148</span></a></p><p id="par0800" class="elsevierStylePara elsevierViewall">The presence of severe renal damage associated with NSAIDs is a rare event&#44; with little information about its occurrence and risk factors&#46;</p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Other Relevant Aspects</span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Anemia</span><p id="par0805" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0155"></elsevierMultimedia></p><p id="par0820" class="elsevierStylePara elsevierViewall">NSAID use is associated with GI bleeding made clinically apparent by hematemesis&#44; melena or rectal bleeding&#44; but also hidden GI bleeding and anemia&#46; The origin of this occult blood loss may be due to mucosal lesions that affect the entire GI tract&#44; from the stomach to the small intestine and the colon&#46;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">149</span></a> Different studies in healthy volunteers have demonstrated the appearance of petechiae&#44; intraluminal blood and mucous substance losses compatible with erosions and ulcers in the small intestine&#46; In these studies it has been observed that ibuprofen or naproxen with a PPI were more associated with these injuries than celecoxib at doses of 400<span class="elsevierStyleHsp" style=""></span>mg&#47;day or placebo&#46;<a class="elsevierStyleCrossRefs" href="#bib0530"><span class="elsevierStyleSup">106&#44;107</span></a> In patients on chronic NSAIDs or coxibs it has also been seen&#44; by capsule endoscopy&#44; that 40&#37;<a class="elsevierStyleCrossRefs" href="#bib0750"><span class="elsevierStyleSup">150&#44;151</span></a> of them had lesions in the small intestine&#44; although the frequency was numerically lower in patients treated with coxibs&#46; The CONDOR<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">103</span></a> study showed that patients with osteoarthritis or rheumatoid arthritis treated with celecoxib 200<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h had 4 times the risk of developing lower hematocrit or hemoglogin decreases &#40;&#62;2<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41; of GI origin or&#44; presumably&#44; from the small bowel versus diclofenac 75<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h plus omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg&#47;day after 6 months of treatment&#46; This study has been confirmed by another randomized multicenter study&#44; the PROBE trial&#44; designed to compare celecoxib versus traditional NSAIDs associated or not to PPI&#46;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">152</span></a> In the MEDAL program&#44; however&#44; no significant difference between diclofenac etoricoxib and the number of GI tract complications was observed&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">110</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Postoperative</span><p id="par0825" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="tb0160"></elsevierMultimedia></p><p id="par0860" class="elsevierStylePara elsevierViewall">The non-opioid analgesics&#44; paracetamol and NSAIDs are often given with opioids as part of multimodal analgesia after major surgery&#46; The choice of method of postoperative pain relief should be well balanced and combining different drugs and different routes of administration may be employed with the aim of using smaller doses to minimize potential side effects&#46;</p><p id="par0865" class="elsevierStylePara elsevierViewall">A recent systematic review<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">153</span></a> demonstrated a statistically significant reduction in morphine consumption at 24<span class="elsevierStyleHsp" style=""></span>h after surgery&#44; when using combination therapy with acetaminophen or NSAIDs versus placebo&#59; there was also a clear difference between paracetamol and NSAIDs&#44; in favor of the latter&#46; A statistically significant difference was also shown in the level of sedation and the occurrence of adverse effects &#40;post operative nausea and vomiting&#41; with any of the combinations&#44; with no superiority of one over another&#46; In another review<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">154</span></a> renal function was evaluated after administration of NSAIDs for postoperative pain control&#46; In 1459 patients from 23 randomized trials&#44; creatinine clearance &#40;48<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; serum creatinine&#44; urine volume&#44; Na&#47;K urinary and need for dialysis were determined&#46; The results show a decrease in creatinine clearance 16<span class="elsevierStyleHsp" style=""></span>ml&#47;min but no differences in other parameters&#46; Nor difference was seen between NSAIDs or cases of renal failure requiring dialysis were observed&#46;</p><p id="par0870" class="elsevierStylePara elsevierViewall">A single oral dose of celecoxib or etoricoxib<a class="elsevierStyleCrossRefs" href="#bib0775"><span class="elsevierStyleSup">155&#44;156</span></a> &#40;120<span class="elsevierStyleHsp" style=""></span>mg&#41; is effective for postoperative pain relief and adverse events did not differ from placebo&#46;</p><p id="par0875" class="elsevierStylePara elsevierViewall">Dexketoprofen administered parenterally has a similar analgesic efficacy as postoperative ketoprofen and diclofenac&#46;<a class="elsevierStyleCrossRefs" href="#bib0785"><span class="elsevierStyleSup">157&#44;158</span></a> The recommended dose is 50<span class="elsevierStyleHsp" style=""></span>mg every 8<span class="elsevierStyleHsp" style=""></span>or 12<span class="elsevierStyleHsp" style=""></span>h limited to the acute symptomatic period &#40;no more than 2<span class="elsevierStyleHsp" style=""></span>days&#41;&#46; The total daily dose should be limited to 50<span class="elsevierStyleHsp" style=""></span>mg on the following assumptions&#58; &#40;a&#41; in the elderly who have a mild physiological decline in renal function&#44; &#40;b&#41; in patients with mild to moderate hepatic impairment &#40;Child&#8211;Pugh score 5&#8211;9&#41;&#44; which also should be carefully monitored&#44; and &#40;c&#41; for mild renal impairment &#40;creatinine clearance 50&#8211;80<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#41;&#46;</p></span></span></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Summary and Final Recommendations</span><p id="par0880" class="elsevierStylePara elsevierViewall">A summary of the recommendations of this consensus&#44; and the graphic expression of the secondary effects of commonly used NSAIDs are detailed in <a class="elsevierStyleCrossRefs" href="#tbl0025">Tables 5 and 6</a>&#46; Finally&#44; in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a> an algorithm guiding the correct prescription of NSAIDs&#44; based on the presence of different levels of GI and CV risk has been constructed&#44; according to the evidence available in 2013&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Ethical Responsibilities</span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Protection of people and animals</span><p id="par0885" class="elsevierStylePara elsevierViewall">The authors declare that no experiments have been performed on humans or animals&#46;</p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Data confidentiality</span><p id="par0890" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article&#46;</p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Right to privacy and informed consent</span><p id="par0895" class="elsevierStylePara elsevierViewall">The authors state that no patient data appear in this article&#46;</p></span></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflicts of Interest</span><p id="par0900" class="elsevierStylePara elsevierViewall">Dr&#46; Lanas claims to have received research grants from AstraZeneca&#44; Pfizer and Bayer over the past two years&#46; He has also participated in Advisory Board meetings organized by Pfizer and Bayer&#46;</p><p id="par0905" class="elsevierStylePara elsevierViewall">Dr&#46; Calvet states he has participated&#44; for the past two years&#44; in Boards organized by Pfizer&#46;</p><p id="par0910" class="elsevierStylePara elsevierViewall">Dr&#46; P&#46; Benito claims to have received&#44; over the past two years&#44; research grants from Pfizer&#44; Abbott&#44; Roche&#44; UCB and Esteve&#46;</p><p id="par0915" class="elsevierStylePara elsevierViewall">Dr&#46; Garc&#237;a Llorente states that he has participated&#44; for the past two years&#44; at scientific meetings sponsored by Abbott&#44; Pfeizer&#44; UCB&#44; Roche&#44; BMS&#44; as well as a UCB advisory board&#46;</p><p id="par0920" class="elsevierStylePara elsevierViewall">Dr&#46; Blanca Hern&#225;ndez Cruz states that in the past two years she has received research grants&#44; consulting fees paid and fee-for-papers with various companies&#44; the Spanish Society of Rheumatology&#44; Abbott&#44; Roche&#44; Pfizer&#44; MSD and BMS&#46;</p><p id="par0925" class="elsevierStylePara elsevierViewall">The rest of the participants declared no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Introduction"
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        "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This article outlines key recommendations for the appropriate prescription of non steroidal anti-inflammatory drugs to patients with different musculoskeletal problems&#46; These recommendations are based on current scientific evidence&#44; and takes into consideration gastrointestinal and cardiovascular safety issues&#46; The recommendations have been agreed on by experts from three scientific societies &#40;Spanish Society of Rheumatology &#91;SER&#93;&#44; Spanish Association of Gastroenterology &#91;AEG&#93; and Spanish Society of Cardiology &#91;SEC&#93;&#41;&#44; following a two-round Delphi methodology&#46; Areas that have been taken into account encompass&#58; efficiency&#44; cardiovascular risk&#44; gastrointestinal risk&#44; liver risk&#44; renal risk&#44; inflammatory bowel disease&#44; anemia&#44; post-operative pain&#44; and prevention strategies&#46; We propose a patient management algorithm that summarizes the main aspects of the recommendations&#46;</p>"
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        "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Este art&#237;culo se&#241;ala las recomendaciones claves para una adecuada prescripci&#243;n de antiinflamatorios no esteroideos a pacientes que presentan indicaci&#243;n de tratamiento con esta medicaci&#243;n&#44; en base a la evidencia cient&#237;fica actual y teniendo en consideraci&#243;n aspectos de seguridad gastrointestinal y cardiovascular&#46; Las recomendaciones se han consensuado por expertos designados por 3 sociedades cient&#237;ficas &#40;Sociedad Espa&#241;ola de Reumatolog&#237;a&#44; Asociaci&#243;n Espa&#241;ola de Gastroenterolog&#237;a y Sociedad Espa&#241;ola de Cardiolog&#237;a&#41;&#44; siguiendo una metodolog&#237;a Delphi a 2 rondas&#46; Las &#225;reas que se han tenido en cuenta engloban&#58; eficacia&#44; riesgo cardiovascular&#44; riesgo gastrointestinal&#44; riesgo hep&#225;tico&#44; riesgo renal&#44; enfermedad inflamatoria intestinal&#44; anemia&#44; dolor postoperatorio y estrategias de prevenci&#243;n&#46; Se propone un algoritmo de manejo de pacientes que recoge los aspectos fundamentales de las recomendaciones&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Lanas A&#44; Benito P&#44; Alonso J&#44; Hern&#225;ndez-Cruz B&#44; Bar&#243;n-Esquivias G&#44; Perez-A&#237;sa &#193;&#44; et al&#46; Recomendaciones para una prescripci&#243;n segura de antiinflamatorios no esteroideos&#58; documento de consenso elaborado por expertos nominados por 3 sociedades cient&#237;ficas &#40;SER-SEC-AEG&#41;&#46; Reumatol Clin&#46; 2014&#59;10&#58;68&#8211;84&#46;</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Algorithm recommendations for the use of NSAIDs according to the cardiovascular and gastrointestinal risk &#40;upper and lower digestive tract&#41;&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#42;</span> If necessary naproxen&#43;PPI or celecoxib at low doses &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&#177;PPI as soon as possible in both cases&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#42;&#42;</span> More robust information for celecoxib than for etoricoxib</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#35;</span> Naproxen should be taken 2<span class="elsevierStyleHsp" style=""></span>h before ASA&#46; Ifenteric coated aspirin are used&#44; interaction possibilities are greater&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">&#35;&#35;</span> If there is a prior cardiovascular event&#44; EMA and AEM currently contraindicate this option&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">It is assumed that patients with very high cardiovascular risk should be treated with ASA&#46; Therefore&#44; in the group of low gastrointestinal risk&#44; very high cardiovascular risk is not contemplated&#44; because use of ASA&#44; and gastrointestinal risk is intermediate at best&#46;</p>"
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Angel Lanas Arbeloa&#44; Pere Benito Ruiz&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Methodology</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Milena Gobbo Montoya&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Effectiveness</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Directions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Pere Benito Ruiz&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Timing&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Francisco Garc&#237;a Llorente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Quality of life&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blanca Hern&#225;ndez Cruz&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cardiovascular risk</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cardiovascular risk stratification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jos&#233; Ram&#243;n Gonz&#225;lez-Juanatey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Associated cardiovascular complications of NSAID use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Joaqu&#237;n Mart&#237;n Alonso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of anticoagulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gonzalo Bar&#243;n Esquivas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Antiplatelet use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gonzalo Bar&#243;n Esquivas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gastrointestinal risk</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Digestive risk stratification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aisa Angeles P&#233;rez&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Gastrointestinal complications associated with the use of NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aisa Angeles P&#233;rez&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prevention strategies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xavier Calvet Calvo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hepatic risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xavier Calvet Calvo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dyspepsia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Xavier Calvet Calvo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Angel Lanas Arbeloa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Renal risk</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Renal risk stratification&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blanca Hern&#225;ndez Cruz&#44; Francisco Garc&#237;a Llorente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Associated renal complications of NSAID use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Blanca Hern&#225;ndez Cruz&#44; Francisco Garc&#237;a Llorente&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Other relevant aspects</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Jos&#233; Ram&#243;n Gonz&#225;lez-Juanatey&#44; Angel Lanas Arbeloa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Postoperative&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gonzalo Bar&#243;n Esquivas&#44; Pere Benito Ruiz&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Very high</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;a&#41; Cardiovascular disease documented by invasive or non-invasive techniques &#40;coronary angiography&#44; isotope techniques&#44; stress echocardiography and evidence of atherosclerotic plaques by carotid ultrasound&#41;&#44; previous myocardial infarction&#44; previous acute coronary syndrome&#44; coronary revascularization&#44; other revascularization procedures&#44; stroke and peripheral arterial disease&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;b&#41; Diabetes mellitus type 2 or type 1 diabetes mellitus associated with target organ damage &#40;microalbuminuria&#58; 30&#8211;300<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;c&#41; chronic moderate to severe renal disease &#40;estimated glomerular filtration rate &#60;<span class="elsevierStyleHsp" style=""></span>60<span class="elsevierStyleHsp" style=""></span>ml&#47;min&#47;l&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;d&#41; SCORE&#8805;10&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">High</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;a&#41; Any markedly elevated individual risk factor&#44; familial hypercholesterolemia or severe hypertension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#40;b&#41; &#8805;SCORE 5&#37; and &#60;10&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SCORE&#8805;1&#37; and &#60;5&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Low</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SCORE&#60;1&#37; absence of other risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab476188.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Assessment of Cardiovascular Risk&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Accepted risk factors&#58;</span> Age&#62;60&#44; history of complicated and uncomplicated peptic ulcer&#46; Concomitant use of NSAIDs or aspirin plus COXIB with clopidogrel&#44; anticoagulants&#44; corticosteroids or inhibitors of serotonin reuptake&#44; high dose NSAIDs&#44; or 2 NSAID&#44; serious comorbidity&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">High</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>History of complicated peptic ulcers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of anticoagulants or&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Combination&#62;2 other risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Medium</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Nonanticoagulated patients or those with a history of complicated ulcer who have some other isolated risk factor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Low</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Patients without risk factors&#46; Does not take acetylsalicylic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab476189.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Evaluation of Gastrointestinal Risk&#46;</p>"
        ]
      ]
      6 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">GFR&#44; glomerular filtration rate&#59; eGFR&#44; estimated glomerular filtration rate&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Stage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">GFR &#40;ml&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kidney damage with normal GFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">60&#8211;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Kidney damage&#44; slight decrease in eGFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30&#8211;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderate decrease in eGFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">15&#8211;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serious decline in eGFR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;15 or dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Predialysis&#47;dialysis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab476185.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Estimation of Renal Damage&#46;</p>"
        ]
      ]
      7 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">The number of crosses indicates a semi-quantitative assessment of the level of risk vs non-use&#46; The levels of evidence are not identical and sometimes limited &#40;see specific recommendations&#41;&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">ASA&#44; acetylsalicylic acid&#59; ACO&#44; anticoagulants&#59; CV&#44; cardiovascular&#59; GI&#44; gastrointestinal&#59; PPI&#44; proton pump inhibitors&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">NSAID type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Upper GI damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Lower GI damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Use of PPI to protect the upper GI tract&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Interaction with ASA or ACO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">CV risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diclofenac&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ibuprofen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Naproxen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Celecoxib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#8722;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etoricoxib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#63;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">&#43;&#43;&#43;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Summary of the Effects of Different NSAIDs at Anti-inflammatory Doses&#46;</p>"
        ]
      ]
      8 => array:7 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Recommendations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Efficacy</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; <span class="elsevierStyleItalic">Indications&#46;</span> The primary indication for the use of NSAIDs is to decrease pain&#46; No NSAID has proven superior to another&#44; with the efficacy of traditional NSAIDs being similar to that of COXIB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; <span class="elsevierStyleItalic">Timing</span>&#46; Before using NSAIDs&#44; other treatment options should be evaluated&#44; and NSAIDs should always be prescribed at the lowest effective dose for the shortest possible time&#46; Only in very specific cases&#44; such as ankylosing spondylitis&#44; continued long-term use may be justified&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#46; <span class="elsevierStyleItalic">Quality of life</span>&#46; NSAIDs cause an improvement in the quality of life of patients with chronic or acute rheumatic disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Cardiovascular risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; <span class="elsevierStyleItalic">Cardiovascular risk stratification&#46;</span> All patients taking NSAIDs chronically should undergo an estimate of cardiovascular risk &#40;CV&#41; at least once a year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; <span class="elsevierStyleItalic">Cardiovascular complications associated with NSAID use&#46;</span> Administration of NSAIDs is associated with an increased risk of developing acute coronary syndrome &#40;ACS&#41; or other atherothrombotic cardiovascular events &#40;stroke and peripheral arterial problems&#41;&#46; The increased cardiovascular risk varies greatly depending on the type of NSAID used&#44; naproxen being one of the safest&#44; while rofecoxib&#44; diclofenac&#44; etodolac and indomethacin are associated with increased cardiovascular risk&#46; Etoricoxib and diclofenac have a similar CV profile&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#46; <span class="elsevierStyleItalic">Use of anticoagulants&#46;</span> The combination of anticoagulants &#40;warfarin&#44; coumarin derivatives&#44; etc&#46;&#41; and NSAIDs should be avoided&#46; If absolutely necessary&#44; COXIB appear to be associated with a lower risk of bleeding complications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&#46; <span class="elsevierStyleItalic">Use of antiplatelet&#46;</span> Avoid the use of NSAIDs&#44; even in the short term in patients with acute myocardial infarction before taking ASA as it is associated with increased cardiovascular risk&#46; In patients taking low-dose aspirin&#44; the association with ibuprofen and naproxen interferes with the antiplatelet effect of aspirin&#44; so one should avoid using them together&#46; In patients taking aspirin to prevent cardiovascular events requiring chronic treatment with NSAIDs&#44; coxibs are a therapeutic option to consider&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Gastrointestinal risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; <span class="elsevierStyleItalic">Gastrointestinal risk stratification&#46;</span> A custom profile assessment of baseline gastrointestinal risk of each patient and the NSAID to use should be performed&#46; Patients over 60 years of age are a risk factor by themselves for the occurrence of gastrointestinal complications in patients taking NSAIDs&#44; and this risk increases progressively with age&#46; The presence of a history of gastroduodenal ulcer&#44; complicated or uncomplicated peptic ulcer is a risk factor for the development of gastrointestinal complications in patients taking NSAIDs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; <span class="elsevierStyleItalic">Gastrointestinal complications associated with NSAID use&#46;</span> It is not recommended to use two or more NSAID simultaneously&#44; since there is increased efficiency and instead increases toxicity&#46; The risk of gastrointestinal complications increases if high doses of NSAIDs are used in a sustained manner&#46; This risk is constant regardless of the dose&#44; for as long as the treatment is continued&#46; NSAID use is associated with increased risk of lesion and complications of upper and lower gastrointestinal tract&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>3&#46; <span class="elsevierStyleItalic">Prevention strategies&#46;</span> The use of H2-antagonist receptors for the prevention of gastrointestinal complications of NSAIDs is not recommended&#46; The use of inhibitors of the proton pump &#40;PPI&#41; associated with a non-selective NSAID is a valid strategy for prevention of gastrointestinal complications of NSAIDs in patients at risk&#44; with coxibs &#40;celecoxib being the one with available data&#41; being preferrable over the combination of a nonselective NSAID with a PPI in the prevention of gastrointestinal tract lesions&#46; Using a COXIB reduces complications in the upper and lower gastrointestinal tract&#46; The use of low dose aspirin increases 2&#8211;4 times the risk of complications&#44; so patients with gastrointestinal risk factors should receive gastroprotection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>4&#46; <span class="elsevierStyleItalic">Hepatic risk&#46;</span> In patients treated with NSAIDs severe liver toxicity is rare and no special monitoring measures are recommended&#46; In patients with liver cirrhosis avoidance of NSAIDs is recommended&#44; and in the event that it becomes absolutely essential&#44; the use of a COXIB is recommended for the shortest possible time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>5&#46; <span class="elsevierStyleItalic">Dyspepsia&#46;</span> In patients with dyspepsia associated with nonselective NSAIDs or coxibs&#44; treatment with a PPI is recommended as the drug of choice&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>6&#46; <span class="elsevierStyleItalic">Inflammatory bowel disease&#46;</span> In patients with inflammatory bowel disease&#44; NSAIDs should be avoided&#44; and if necessary&#44; their use should be limited to quiescent phases of the disease&#44; the use of coxibs is recommended at low doses and for a short time&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Renal risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; <span class="elsevierStyleItalic">Renal risk stratification&#46;</span> In chronic rheumatic disease patients receiving NSAIDs&#44; renal function should be assessed by estimating glomerular filtration rate at least once a year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; <span class="elsevierStyleItalic">Renal complications associated with NSAID use</span>&#46; Patients with stage 3 chronic kidney disease&#44; or associated renal and&#47;or cardiovascular comorbidity&#44; NSAIDs should not be used&#44; except in special situations and with close clinical monitoring&#44; and NSAID doses higher than those recommended should be avoided&#46; In patients with CKD stages 4 and 5&#44; the use of NSAIDs is contraindicated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Other relevant aspects</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1&#46; <span class="elsevierStyleItalic">Anemia&#46;</span> The development of anemia or a hemoglobin decrease &#62;2<span class="elsevierStyleHsp" style=""></span>g&#47;dL is common in patients who take NSAIDs&#44; even if associated with PPI&#46; Treatment with celecoxib is less likely to be associated with this side effect&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>2&#46; <span class="elsevierStyleItalic">Postoperatively&#46;</span> We recommend the use of a paracetamol-NSAID combination for short term postoperative pain&#44; provided there is no contraindication for the administration of the latter&#46; One NSAID cannot be prioritized over another regarding their postoperative use&#46; The combination in terms of dose and type of drug used in the postoperative period must be balanced empirically&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Summary of Consensus Recommendations&#46;</p>"
        ]
      ]
      9 => array:5 [
        "identificador" => "tb0005"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The main indication for the use of NSAIDs is to decrease the pain</span>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE &#40;Level of Evidence&#41;&#58; 3&#44; DR &#40;degree of Recommendation&#41;&#58; D&#44; LA &#40;Level of Agreement&#41;&#58; 78&#37;</span></p></span>"
        ]
      ]
      10 => array:5 [
        "identificador" => "tb0010"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">No NSAID has been shown to be superior to another&#44; and the efficacy of traditional NSAIDs is similar to that of coxibs</span>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 3&#44; DR&#58; D&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      11 => array:5 [
        "identificador" => "tb0015"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">NSAIDs should be prescribed at the lowest effective dose and for the shortest possible time</span>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In general&#44; one should consider other treatment options before prescribing NSAIDs</span>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE 4&#44; DR&#58; D&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      12 => array:5 [
        "identificador" => "tb0020"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
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        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0140" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The continued long-term use with NSAIDs may be justified in certain conditions&#44; such as ankylosing spondylitis</span>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      13 => array:5 [
        "identificador" => "tb0025"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0160" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">NSAIDs lead to an improvement in the quality of life of patients with chronic or acute rheumatic pathology</span>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      14 => array:5 [
        "identificador" => "tb0030"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0185" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In all patients taking NSAIDs chronically CV risk estimation should be performed</span>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 89&#37;</span></p><p id="par0195" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">CV risk estimation should be performed systematically in all patients who chronically used NSAIDs at least once a year</span>&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE 4&#44; DR&#58; D&#44; LA&#58; 78&#37;</span></p></span>"
        ]
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      15 => array:5 [
        "identificador" => "tb0035"
        "tipo" => "MULTIMEDIATEXTO"
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        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The administration of NSAIDs is associated with an increased risk of developing acute coronary syndrome &#40;ACS&#41; or other character atherothrombotic CV events &#40;stroke and peripheral arterial problems&#41;</span>&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      16 => array:5 [
        "identificador" => "tb0040"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0240" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The increase in CV risk varies greatly depending on the type of NSAID used</span>&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p><p id="par0250" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Naproxen is one of the safest NSAID in terms of CV risk</span>&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p><p id="par0260" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Rofecoxib&#44; diclofenac&#44; indomethacin&#44; etodolac etoricoxib and NSAIDs are the drugs most associated to CV risk</span>&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      17 => array:5 [
        "identificador" => "tb0045"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0290" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The combination of anticoagulants &#40;warfarin&#44; coumarin derivatives&#44; etc&#46;&#41; and NSAIDs should be avoided&#46; If absolutely necessary&#44; COXIB appear to be associated with a lower risk of bleeding complications</span>&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      18 => array:5 [
        "identificador" => "tb0050"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0320" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Avoid the use of NSAIDs&#44; even in the short term&#44; in patients with acute myocardial infarction taking ASA as it is associated with an increased CV risk</span>&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; B&#44; LA&#58; 78&#37;</span></p><p id="par0330" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients taking low-dose aspirin&#44; the association with ibuprofen and naproxen interferes with the antiplatelet effect of aspirin&#44; so one should avoid using them together</span>&#46;</p><p id="par0335" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; C&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      19 => array:5 [
        "identificador" => "tb0055"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0350" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients taking aspirin to prevent CV events requiring chronic treatment with NSAIDs&#44; coxibs are a therapeutic option to consider</span>&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 78&#37;</span></p></span>"
        ]
      ]
      20 => array:5 [
        "identificador" => "tb0060"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0370" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">A custom profile assessment baseline of the GI risk of each patient and NSAID use should be performed</span>&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE 4&#44; DR&#58; D&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      21 => array:5 [
        "identificador" => "tb0065"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0385" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients over 60 years of age constitute a risk factor by itself due to the occurrence of GI complications in patients taking NSAIDs&#44; and this risk increases progressively with age</span>&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 100</span>&#37;</p></span>"
        ]
      ]
      22 => array:5 [
        "identificador" => "tb0070"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0400" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The presence of a history of complicated or uncomplicated gastroduodenal or peptic ulcer is a risk factor for the development of GI complications in patients taking NSAIDs</span>&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      23 => array:5 [
        "identificador" => "tb0075"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0415" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">It is not recommended to use 2 or more NSAIDs simultaneously&#44; since concomitant use does not increase the effectiveness and it does increase toxicity</span>&#46;</p><p id="par0420" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      24 => array:5 [
        "identificador" => "tb0080"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0440" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The risk of GI complications increases if high doses of NSAIDs are used in a sustained manner</span>&#46;</p><p id="par0445" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p><p id="par0450" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The risk of GI complications is constant throughout the time that treatment with NSAID is maintained</span>&#46;</p><p id="par0455" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2 -&#44; DR&#58; C&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      25 => array:5 [
        "identificador" => "tb0085"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0465" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Co-administration of aspirin and acetaminophen do not appear to increase the gastroduodenal mucosal damage with respect to the use of aspirin alone so&#44; if necessary&#44; can be jointly employed in these circumstances</span>&#46;</p><p id="par0470" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#8722;&#44; DR&#58; B&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      26 => array:5 [
        "identificador" => "tb0090"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0490" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">NSAID use is associated with increased risk of injury and complications of the upper and lower GI tract</span>&#46;</p><p id="par0495" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      27 => array:5 [
        "identificador" => "tb0095"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0515" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">H2 antagonist use for prevention of GI complications of NSAIDs is not recommended</span>&#46;</p><p id="par0520" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      28 => array:5 [
        "identificador" => "tb0100"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0530" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">PPI associated with a nonselective NSAID is valid strategy for the prevention of high GI complications of NSAIDs in patients at risk</span>&#46;</p><p id="par0535" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#43;&#44; DR&#58; A&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      29 => array:5 [
        "identificador" => "tb0105"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0545" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Coxibs are superior to the combination of classical NSAIDs with a PPI in preventing injury of the GI tract</span>&#46;</p><p id="par0550" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      30 => array:5 [
        "identificador" => "tb0110"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0560" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The use of a COXIB reduces complications in the upper and lower GI tract</span>&#46;</p><p id="par0565" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      31 => array:5 [
        "identificador" => "tb0115"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0580" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The use of low dose aspirin increases 2&#8211;4 times the risk of GI complications&#44; so patients with GI risk factors should be prescribed gastroprotection</span>&#46;</p><p id="par0585" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      32 => array:5 [
        "identificador" => "tb0120"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0610" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients treated with NSAIDs&#44; severe liver toxicity is rare&#44; so no special monitoring measures are recommended</span>&#46;</p><p id="par0615" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      33 => array:5 [
        "identificador" => "tb0125"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0625" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients with liver cirrhosis it is recommended to avoid the use of NSAIDs</span>&#46;</p><p id="par0630" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      34 => array:5 [
        "identificador" => "tb0130"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0640" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">If treatment with NSAIDs is absolutely essential in patients with liver cirrhosis&#44; using a COXIB is recommended for the shortest period of time possible</span>&#46;</p><p id="par0645" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 89&#37;</span></p></span>"
        ]
      ]
      35 => array:5 [
        "identificador" => "tb0135"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0660" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients with nonselective NSAID or coxib treatment-associated dyspepsia&#44; a PPI is recommended as the drug of first choice</span>&#46;</p><p id="par0665" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#43;&#44; DR&#58; A&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      36 => array:5 [
        "identificador" => "tb0140"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0680" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients suffering from inflammatory bowel disease &#40;IBD&#41;&#44; the use of NSAIDs should be avoided</span>&#46;</p><p id="par0685" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#8722;&#44; DR&#58; B&#44; LA&#58; 89&#37;</span></p><p id="par0690" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients suffering from IBD and if it should be necessary to use NSAIDs in quiescent phases of the disease&#44; the use of COXIBs is recommended at low doses for a short time&#46;</span></p><p id="par0695" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#8722;&#44; DR&#58; B&#44; LA&#58; 100&#37;</span></p></span>"
        ]
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      37 => array:5 [
        "identificador" => "tb0145"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0710" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In chronic rheumatic patients receiving NSAIDs&#44; renal function should be assessed by estimating glomerular filtration rate</span>&#46;</p><p id="par0715" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 89&#37;</span></p><p id="par0720" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In chronic rheumatic patients receiving NSAIDs&#44; renal function should be assessed at least once a year&#46;</span></p><p id="par0725" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 100&#37;</span></p></span>"
        ]
      ]
      38 => array:5 [
        "identificador" => "tb0150"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0750" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients with chronic kidney disease stage 3 or renal comorbidity and&#47;or associated CV&#44; use of NSAIDs&#44; except in special situations and with close clinical monitoring&#44; is not recommended</span>&#46;</p><p id="par0755" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 100&#37;</span></p><p id="par0760" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients with chronic kidney disease stage 3 or renal comorbidity and&#47;or associated CV&#44; the use of higher doses than recommended of NSAIDs should be avoided&#44; especially COXIB&#46;</span></p><p id="par0765" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 89&#37;</span></p><p id="par0770" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">In patients with chronic kidney disease stage 4 and 5 NSAID use is contraindicated&#46;</span></p><p id="par0775" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#44; DR&#58; C&#44; LA&#58; 78&#37;</span></p></span>"
        ]
      ]
      39 => array:5 [
        "identificador" => "tb0155"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0810" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The development of anemia or hemoglobin decreases<span class="elsevierStyleMonospace">&#62;</span>2<span class="elsevierStyleHsp" style=""></span>g&#47;dL is common in patients who take NSAIDs&#44; even associated with PPI&#46; Treatment with celecoxib was associated with a lower likelihood of developing this adverse effect</span>&#46;</p><p id="par0815" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 100</span>&#37;</p></span>"
        ]
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      40 => array:5 [
        "identificador" => "tb0160"
        "tipo" => "MULTIMEDIATEXTO"
        "mostrarFloat" => false
        "mostrarDisplay" => true
        "texto" => array:1 [
          "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0830" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">We recommend the use of paracetamol&#8211;NSAID combination in postoperative pain in the short term&#44; provided there is no contraindication to the administration of the latter</span>&#46;</p><p id="par0835" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 1&#43;&#44; DR&#58; A&#44; LA&#58; 78&#37;</span></p><p id="par0840" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">One NSAID cannot be prioritized over another regarding their postoperative use</span>&#46;</p><p id="par0845" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 2&#43;&#43;&#44; DR&#58; B&#44; LA&#58; 89&#37;</span></p><p id="par0850" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The combination in terms of dose and type of drug use in the postoperative period must be balanced empirically</span>&#46;</p><p id="par0855" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">LE&#58; 3&#44; DR&#58; D&#44; LA&#58; 78&#37;</span></p></span>"
        ]
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    ]
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      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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              "identificador" => "bib0005"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "European Medicines Agency review concludes positive benefit-risk balance for non-selective NSAIDs"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [ …3]
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              "identificador" => "bib0010"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Estrategia cl&#237;nica para la prevenci&#243;n de los efectos adversos sobre el tracto digestivo de los antiinflamatorios no esteroideos"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [ …5]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical strategy to prevent the gastrointestinal adverse effects of nonsteroidal anti-inflammatory agents"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Appropriate use of non-steroidal anti-inflammatory drugs in rheumatology&#58; guidelines from the Spanish Society of Rheumatology and the Mexican College of Rheumatology"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1699-258X(09)70197-4"
                      "Revista" => array:6 [ …6]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "SIGN Scottish Intercollegiate Guidelines Network"
                      "autores" => array:1 [ …1]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [ …3]
                    ]
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              ]
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            5 => array:3 [
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2013.10.008

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