Published Online
on June 14, 2004

A more recent version of this article appeared on June 22, 2004

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Submitted on January 12, 2004
Revised on April 22, 2004
Accepted on April 27, 2004

Nonsteroidal Antiinflammatory Drugs and the Risk of Myocardial Infarction in the General Population

Luis A. García Rodríguez MD, MSc^*, Cristina Varas-Lorenzo MD, MSc, PhD, Andrew Maguire MSc, BSc (Hons), and Antonio González-Pérez MSc, BPharm

From Centro Español de Investigación Farmacoepidemiológica (L.A.G.R., A.G.-P.), Madrid, and Pfizer (C.V.-L., A.M.), Global Epidemiology, Barcelona, Spain.

^* To whom correspondence should be addressed. E-mail: lagarcia{at}ceife.es.

Background--Nonsteroidal antiinflammatory drugs (NSAIDs) are reversible inhibitors of cyclooxygenase (COX)-1 and COX-2. Whether transient and incomplete COX-1 inhibition with NSAIDs other than aspirin will translate into clinical cardioprotection is unclear. Some reports suggest that concurrent aspirin and ibuprofen might be associated with lower cardioprotection than aspirin alone because of a pharmacodynamic interaction.

Methods and Results----We conducted a cohort study with a nested case-control analysis. Overall, 4975 cases of acute myocardial infarction (MI) and death from coronary heart disease (CHD) were identified (January 1997 to December 2000) in the UK. A total of 20 000 controls were randomly sampled, and frequency was matched to cases by age, sex, and calendar year. The incidence rate was 5.0 per 1000 person-years. The multivariate-adjusted OR for current NSAID use compared with nonuse was 1.07 (95% CI, 0.95 to 1.20). Treatment duration or daily dose did not change the results. The effect was similar among patients free of CHD history (1.04; 95% CI, 0.90 to 1.20) and patients with previous history (1.12; 95% CI, 0.91 to 1.38). Estimates for individual NSAIDs were all comparable, with no major effect on the risk of acute MI. Naproxen was associated with an OR of 0.89 (95% CI, 0.64 to 1.24). The OR of aspirin and concurrent NSAIDs use was 1.10 (95% CI, 0.89 to 1.37) compared with aspirin alone. We observed the same result when analyzing ibuprofen and aspirin taken concomitantly.

Conclusions--This study could not demonstrate any detectable risk reduction of NSAIDs on the occurrence of MI. Our results do not support the existence of a clinically meaningful interaction between aspirin and NSAIDs, including ibuprofen.

Key words: myocardial infarction • aspirin • epidemiology

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