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Muhammad Mamdani, PharmD, MA, MPH; Paula Rochon, MD, MPH; David N. Juurlink, MD; Geoffrey M. Anderson, MD, PhD; Alex Kopp, BA; Gary Naglie, MD; Peter C. Austin, PhD; Andreas Laupacis, MD, MSc

Arch Intern Med. 2003;163:481-486.

Background  Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium. We compared the rates of acute myocardial infarction (AMI) among elderly patients dispensed selective cyclooxygenase 2 inhibitors, naproxen, and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods  We conducted a population-based retrospective cohort study using administrative health care data from Ontario, Canada, from April 1, 1998, to March 31, 2001. We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib (n = 15 271), rofecoxib (n = 12 156), naproxen (n = 5669), and nonnaproxen nonselective NSAIDs (n = 33 868), along with a randomly selected control cohort not exposed to NSAIDs (n = 100 000). Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders.

Results  Relative to control subjects, the multivariate model showed no significant differences in AMI risk for new users of celecoxib (adjusted rate ratio [aRR], 0.9; 95% confidence interval [CI], 0.7-1.2), rofecoxib (aRR, 1.0; 95% CI, 0.8-1.4), naproxen (aRR, 1.0; 95% CI, 0.6-1.7), or nonnaproxen nonselective NSAIDs (aRR, 1.2; 95% CI, 0.9-1.4).

Conclusions  The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice. Furthermore, the findings do not support a short-term reduced risk of AMI with naproxen.

From the Institute for Clinical Evaluative Sciences (Drs Mamdani, Rochon, Juurlink, Anderson, Naglie, Austin, and Laupacis and Mr Kopp); Faculty of Pharmacy (Dr Mamdani) and the Departments of Medicine (Drs Rochon, Juurlink, Naglie, and Laupacis), Health Policy, Management, and Evaluation (Dr Anderson), and Public Health Sciences (Dr Austin), Faculty of Medicine, University of Toronto; Division of General Internal Medicine, Sunnybrook and Women's College Health Sciences Centre (Drs Juurlink and Laupacis); Department of Geriatric Medicine, University Health Network and Toronto Rehabilitation Institute (Dr Naglie); and Department of Geriatric Medicine, Baycrest Centre for Geriatric Care (Dr Rochon), Toronto, Ontario. In the past 2 years, Dr Mamdani has conducted research in an unrelated content area at the request of an academic institution whose funding was supported by Pharmacia Corporation (Peapack, NJ), but none of the funding for this study was provided by any pharmaceutical company.

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