Risk of Acute MI With NSAIDs

Study Questions:

What are the determinants, time course, and risks of acute myocardial infarction (AMI) associated with use of oral nonsteroidal anti-inflammatory drugs (NSAIDs)?

Methods:

The investigators performed a systematic review followed by a one-stage Bayesian individual patient data meta-analysis. Studies from Canadian and European healthcare databases were included. Eligible studies were sourced from computerized drug prescription or medical databases, conducted in the general or an elderly population, documented AMI as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of AMI in NSAID users with nonusers, allowed for time-dependent analyses, and minimized effects of confounding and misclassification bias. Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first AMI after study entry for each category of NSAID use at index date (date of AMI for cases, matched date for controls) versus nonuse in the preceding year, and the posterior probability of AMI.

Results:

A cohort of 446,763 individuals including 61,460 with AMI was acquired. Taking any dose of NSAIDs for 1 week, 1 month, or >1 month was associated with an increased risk of MI. With use for 1-7 days, the probability of increased MI risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91-1.82) for celecoxib, 1.48 (1.00-2.26) for ibuprofen, 1.50 (1.06-2.04) for diclofenac, 1.53 (1.07-2.33) for naproxen, and 1.58 (1.07-2.17) for rofecoxib. Greater risk of MI was documented for higher dose of NSAIDs. With use for longer than 1 month, risks did not appear to exceed those associated with shorter durations.

Conclusions:

The authors concluded that all NSAIDs, including naproxen, were found to be associated with an increased risk of AMI.

Perspective:

This meta-analysis of individual patient data found that current use of a NSAID was associated with a significantly increased risk of AMI for all traditional NSAIDs, including naproxen. Since the onset of risk of AMI occurred in the first week and appeared greatest in the first month of treatment with higher doses, clinicians should consider weighing the risks and benefits of NSAIDs before instituting treatment, particularly with higher doses. A major limitation of this database study is that it measured drug dispensing or drug prescribing and not actual drug intake. Despite this limitation, there is now robust evidence of cardiovascular risks with NSAIDs with the risk attributed to celecoxib similar to other NSAIDs.

Clinical Topics: Acute Coronary Syndromes, Geriatric Cardiology, Prevention

Keywords: Acute Coronary Syndrome, Anti-Inflammatory Agents, Non-Steroidal, Diclofenac, Drug Prescriptions, Geriatrics, Ibuprofen, Lactones, Myocardial Infarction, Naproxen, Outcome Assessment (Health Care), Primary Prevention, Risk Assessment, Risk Factors


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