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

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.