Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials
- 1Department of Cardiology, Queen Alexandra Hospital, Portsmouth, UK
- 2Department of Rheumatology, Kings College London School of Medicine, London, UK
- Professor D L Scott, Department of Rheumatology, Kings College London School of Medicine, Weston Education Centre, Kings College London, 10 Cutcombe Road, London SE5 9RS, UK;
- Accepted 18 February 2007
- Published Online First 7 March 2007
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.
Competing interests: PAS, GHK and CMS have received no direct payments from companies involved in the evaluation or marketing of non-steroidal anti-inflammatory drugs in the last 5 years, including support to attend meetings, fees for consulting, and funding for research or educational support. EHC and DLS have received clinical trial grants, unrestricted educational grants and personal sponsorship for attending meetings from many companies involved in clinical trials and marketing of current anti-rheumatic drugs, including all those involved in cyclo-oxygenase-2-specific drugs. DLS has received fees for speaking at meetings, membership of national and international advisory boards, and giving professional advice from many pharmaceutical companies in the last 5 years including Amgen, Merck Sharp and Dhome, Novartis, Pfizer, Sumitomo Pharmaceuticals and Wyeth. He is medical adviser to Arthritis Care and Medical Vice-Chair of the Arthritis and Musculoskeletal Alliance, which have both received unrestricted grants from pharmaceutical companies. No pharmaceutical company or adviser or representative has been involved directly or indirectly in the inception, preparation or writing of this manuscript; its contents have not been disclosed to any pharmaceutical company before submission.
Contributions to authorship: conception, DLS, PAS, GHK; design, CMS, EHC; analysis/interpretation of data, PAS, DLS, EHC; drafting article, PAS, GHK, DLS; critical revisions, all authors.
- myocardial infarction
- non-steroidal anti-inflammatory drug
- odds ratio
- randomised controlled trial
- relative risk