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

P A Scott ¹, G H Kingsley ², C M Smith ², E H Choy ² and D L Scott ^2*

¹ Portsmouth Hospitals NHS Trust, United Kingdom
² Kings College London, United Kingdom

^* To whom correspondence should be addressed. E-mail: david.l.scott{at}kcl.ac.uk.

Accepted 18 February 2007

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.

Keywords: adverse events, coxibs, myocardial infarctions, NSAIDs, systematic review

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