Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials

Ann Rheum Dis. 2007 Oct;66(10):1296-304. doi: 10.1136/ard.2006.068650. Epub 2007 Mar 7.

Abstract

Objective: The comparative risk of myocardial infarction (MI) with cyclo-oxygenase-2-specific drugs and traditional non-steroidal anti-inflammatory drugs (NSAIDs) was determined.

Methods: The results of studies of a suitable size in colonic adenoma and arthritis-that had been published in English and from which crude data about MIs could be extracted-were evaluated. Medline, Embase and Cinahl (2000-2006) databases, as well as published bibliographies, were used as data sources. Systematic reviews examined MI risks in case-control and cohort studies, as well as in randomised controlled trials (RCTs).

Results: 14 case-control studies (74 673 MI patients, 368 968 controls) showed no significant association of NSAIDs with MI in a random-effects model (OR 1.17; 95% CI 0.99 to 1.37) and a small risk of MI in a fixed-effects model (OR 1.32; 95% CI 1.29 to 1.35). Sensitivity analyses showed higher risks of MI in large European studies involving matched controls. Six cohort studies (387 983 patient years, 1 120 812 control years) showed no significant risk of MI with NSAIDs (RR 1.03; 95% CI 1.00 to 1.07); the risk was higher with rofecoxib (RR 1.25; 95% CI 1.17 to 1.34) but not with any other NSAIDs. Four RCTs of NSAIDs in colonic adenoma (6000 patients) showed an increased risk of MI (RR 2.68; 95% CI 1.43 to 5.01). Fourteen RCTs in arthritis (45 425 patients) showed more MIs with cyclo-oxygenase-2-specific drugs (Peto OR 1.6; 95% CI 1.1 to 2.4), but fewer serious upper gastrointestinal events (Peto OR 0.40; 95% CI 0.31 to 0.53).

Conclusion: The overall risk of MI with NSAIDs and cyclo-oxygenase-2-specific drugs was small; rofecoxib showed the highest risk. There was an increased MI risk with cyclo-oxygenase-2-specific drugs compared with NSAIDs, but less serious upper gastrointestinal toxicity.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adenoma / drug therapy
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Arthritis / drug therapy
  • Colonic Neoplasms / drug therapy
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Myocardial Infarction / chemically induced*
  • Randomized Controlled Trials as Topic
  • Research Design
  • Risk Assessment

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors