Published Online
on March 13, 2006

A more recent version of this article appeared on March 28, 2006

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Submitted on October 17, 2005
Revised on December 21, 2005
Accepted on January 11, 2006

Nonsteroidal Antiinflammatory Drugs, Acetaminophen, and the Risk of Cardiovascular Events

Andrew T. Chan MD, MPH^*, JoAnn E. Manson MD, DrPH, Christine M. Albert MD, MPH, Claudia U. Chae MD, MPH, Kathryn M. Rexrode MD, MPH, Gary C. Curhan MD, ScD, Eric B. Rimm ScD, Walter C. Willett MD, DrPH, and Charles S. Fuchs MD, MPH

From the Gastrointestinal Unit (A.T.C.) and Cardiology Division (C.U.C.), Massachusetts General Hospital and Harvard Medical School; Divisions of Cardiology (C.M.A.) and Preventive Medicine (J.E.M., C.M.A., C.U.C., K.M.R.) and Channing Laboratory (A.T.C., J.E.M., G.C.C., E.B.R., W.C.W., C.S.F.), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School; Departments of Epidemiology (J.E.M., G.C.C., E.B.R., W.C.W.) and Nutrition (G.C.C., E.B.R., W.C.W.), Harvard School of Public Health; and Department of Medical Oncology, Dana-Farber Cancer Institute (C.S.F.), Boston, Mass.

^* To whom correspondence should be addressed. E-mail: achan{at}partners.org.

Background--Although randomized trials of cyclooxygenase-2 (COX-2) inhibitors have shown increased cardiovascular risk, studies of nonselective, nonsteroidal antiinflammatory drugs (NSAIDs) and acetaminophen have been inconsistent.

Methods and Results--We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events (nonfatal myocardial infarction, fatal coronary heart disease, nonfatal and fatal stroke) in a prospective cohort of 70 971 women, aged 44 to 69 years at baseline, free of known cardiovascular disease or cancer, who provided medication data biennially since 1990. During 12 years of follow-up, we confirmed 2041 major cardiovascular events. Women who reported occasional (1 to 21 d/mo) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events. However, after adjustment for cardiovascular risk factors, women who frequently (22 d/mo) used NSAIDs had a relative risk (RR) for a cardiovascular event of 1.44 (95% CI, 1.27 to 1.65) compared with nonusers, whereas those who frequently consumed acetaminophen had a RR of 1.35 (95% CI, 1.14 to 1.59). The elevated risk associated with frequent NSAID use was particularly evident among current smokers (RR=1.82; 95% CI, 1.38 to 2.42) and was absent among never smokers (P_interaction=0.02). Moreover, we observed significant dose-response relations: Compared with nonusers, the RRs for a cardiovascular event among women who used 15 tablets per week were 1.86 (95% CI, 1.27 to 2.73) for NSAIDs and 1.68 (95% CI, 1.10 to 2.58) for acetaminophen.

Conclusions--Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events, although more moderate use did not confer substantial risk.

Key words: acetaminophen • aspirin • cardiovascular diseases • cyclooxygenase-2 inhibitors • nonsteroidal antiinflammatory drugs

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