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

Abstract

Objective: Determining the comparative risk of myocardial infarctions (MIs) with COXIBs (Cox-2 specific NSAIDs) and traditional non-steroidal anti-inflammatory drugs (NSAIDs).

Design: Systematic reviews (SRs) examined MI risks in case-control and cohort studies and randomised controlled trials (RCTs) in colonic adenomas and arthritis.

Data sources: MEDLINE, EMBASE, and CINAHL (1998- 2006) and published bibliographies.

Review Methods: We evaluated studies in English of suitable size from which crude data about MIs could be extracted.

Results: 14 case-control studies (74,673 MI patients, 368,968 controls) showed no significant association of NSAIDs with MIs in a random effects model (OR 1.17; 95% CI 0.99, 1.37) and a small risk in a fixed effects model (OR 1.32, 95% CI 1.29, 1.35). Sensitivity analyses showed higher risks in large, European studies involving matched controls. 6 cohort studies (387,983 patient years, 1,120,812 control years) showed no significant risk of MIs with NSAIDs (RR 1.03; 95% CI 1.00, 1.07); risks were higher with rofecoxib (RR 1.25; 95%CI 1.17, 1.34) but not other NSAIDs. 4 RCTs of NSAIDs in colonic adenomas (6000 patients) showed increased MI risks with NSAIDs (RR 2.68: 95% CI 1.43, 5.01). 14 RCTs in arthritis (45,425 patients) showed more MIs with COXIBs (Peto OR 1.6; 95% CI 1.1, 2.4), but fewer serious upper gastrointestinal events (Peto OR 0.40; 95% CI 0.31, 0.53).

Conclusion: Overall risks of MIs with NSAIDs and COXIBs were small; only rofecoxib showed increased MI risks in all studies. Although there was an increased MI risk in COXIBs compared to NSAIDs the incidence of serious upper gastrointestinal toxicity was reduced.