Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events.
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.


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 (> or =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 (Pinteraction=0.02). Moreover, we observed significant dose-response relations: Compared with nonusers, the RRs for a cardiovascular event among women who used > or =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.
Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. achan@partners.org
Andrew T
AT
Chan
JoAnn E
JE
Manson
Christine M
CM
Albert
Claudia U
CU
Chae
Kathryn M
KM
Rexrode
Gary C
GC
Curhan
Eric B
EB
Rimm
Walter C
WC
Willett
Charles S
CS
Fuchs
D000082:Acetaminophen / Q000009:adverse effects*; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D011795:Surveys and Questionnaires
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D000082:Acetaminophen