title: NSAID use selectively increases the risk of non-fatal myocardial infarction: a systematic review of randomised trials and observational studies.
abstract: BACKGROUND
  Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.
  
  
  OBJECTIVE
  We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.
  
  
  METHODS
  We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.
  
  
  RESULTS
  NSAID therapy carried a RR of 1.30 (95% CI, 1.20-1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89-1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%-42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%-98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04-2.50) and 0.86 (95% CI 0.51-1.47) for fatal MIs.
  
  
  CONCLUSIONS
  NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi.
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain. lagarcia@ceife.es
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: García Rodríguez
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.forename: Héctor
authors.initials: H
authors.lastname: Bueno
authors.forename: John
authors.initials: J
authors.lastname: Hwa
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D006801:Humans; D009203:Myocardial Infarction / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal