title: Meta-analysis: cardiovascular events associated with nonsteroidal anti-inflammatory drugs.
abstract: OBJECTIVE
  We performed a meta-analysis of randomized controlled trials to assess the effect of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) on cardiovascular events in trials of joint disease and Alzheimer's disease.
  
  
  METHODS
  We performed comprehensive searches of MEDLINE, EMBASE, CINAHL and Cochrane databases from 1966 to July 2005, and references of identified articles and reviews. We included randomized placebo-controlled trials of at least 6 weeks duration that evaluated nonselective NSAIDs in trials of joint disease or Alzheimer's disease, and reported at least one cardiovascular event or death. The outcome measured was the composite of death, myocardial infarction or cerebrovascular accident, with the pooled results reported as odds ratios (OR). Subgroup analyses evaluated the difference between trials of joint disease and Alzheimer's disease, and for naproxen and non-naproxen NSAIDs.
  
  
  RESULTS
  Pooled data from 13 trials with 7718 participants showed that nonselective NSAIDs had no significant effect on cardiovascular events (OR 1.3; 95% confidence interval [CI], 0.8 to 2.1). No significant effect was seen for joint disease trials (OR 0.6; 95% CI, 0.2 to 1.7) or Alzheimer disease trials (OR 1.6; 95% CI, 0.9 to 2.7). There was no significant difference in results for naproxen and non-naproxen NSAIDs.
  
  
  CONCLUSIONS
  Nonselective NSAIDs have no significant effect on cardiovascular events or death in trials of joint disease and Alzheimer disease, but a small adverse effect could not be excluded. An indication for risk was present in trials of Alzheimer's disease but not in joint disease trials. There was no significant adverse or cardioprotective effect of naproxen.
authors.affiliation: Stanford University School of Medicine, Stanford, California, USA. salpeter@stanford.edu
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Salpeter
authors.forename: Peter
authors.initials: P
authors.lastname: Gregor
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Ormiston
authors.forename: Richard
authors.initials: R
authors.lastname: Whitlock
authors.forename: Parminder
authors.initials: P
authors.lastname: Raina
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000209:etiology*; D006801:Humans; D007592:Joint Diseases / Q000188:drug therapy; D009288:Naproxen / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen