Circulation. 2004;109:2068-2073
Published online before print April 19, 2004, doi: 10.1161/01.CIR.0000127578.21885.3E
Published online before print April 19, 2004, doi: 10.1161/01.CIR.0000127578.21885.3E
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(Circulation. 2004;109:2068-2073.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Relationship Between Selective Cyclooxygenase-2 Inhibitors and Acute Myocardial Infarction in Older Adults
From the Division of Pharmacoepidemiology and Pharmacoeconomics (D.H.S., S.S., R.J.G., Y.K., R.L., H.M., J.A.) and Division of Rheumatology, Immunology, and Allergy (D.H.S.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Daniel H. Solomon, MD, MPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women’s Hospital, Harvard Medical School, 1620 Tremont St, Suite 3030, Boston, MA 02120. E-mail dhsolomon{at}partners.org
Received October 7, 2003; revision received January 22, 2004; accepted February 5, 2004.
Background— Although cyclooxygenase-2 inhibitors (coxibs) were developed to cause less gastrointestinal hemorrhage than nonselective nonsteroidal antiinflammatory drugs (NSAIDs), there has been concern about their cardiovascular safety. We studied the relative risk of acute myocardial infarction (AMI) among users of celecoxib, rofecoxib, and NSAIDs in Medicare beneficiaries with a comprehensive drug benefit.
Methods and Results— We conducted a matched case-control study of 54 475 patients 65 years of age or older who received their medications through 2 state-sponsored pharmaceutical benefits programs in the United States. All healthcare use encounters were examined to identify hospitalizations for AMI. Each of the 10 895 cases of AMI was matched to 4 controls on the basis of age, gender, and the month of index date. We constructed matched logistic regression models including indicators for patient demographics, healthcare use, medication use, and cardiovascular risk factors to assess the relative risk of AMI in patients who used rofecoxib compared with persons taking no NSAID, taking celecoxib, or taking NSAIDs. Current use of rofecoxib was associated with an elevated relative risk of AMI compared with celecoxib (odds ratio [OR], 1.24; 95% CI, 1.05 to 1.46; P=0.011) and with no NSAID (OR, 1.14; 95% CI, 1.00 to 1.31; P=0.054). The adjusted relative risk of AMI was also elevated in dose-specific comparisons: rofecoxib 
25 mg versus celecoxib 200 mg (OR, 1.21; 95% CI, 1.01 to 1.44; P=0.036) and rofecoxib >25 mg versus celecoxib >200 mg (OR, 1.70; 95% CI, 1.07 to 2.71; P=0.026). The adjusted relative risks of AMI associated with rofecoxib use of 1 to 30 days (OR, 1.40; 95% CI, 1.12 to 1.75; P=0.005) and 31 to 90 days (OR, 1.38; 95% CI, 1.11 to 1.72; P=0.003) were higher than >90 days (OR, 0.96; 95% CI, 0.72 to 1.25; P=0.8) compared with celecoxib use of similar duration. Celecoxib was not associated with an increased relative risk of AMI in these comparisons.
Conclusions— In this study, current rofecoxib use was associated with an elevated relative risk of AMI compared with celecoxib use and no NSAID use. Dosages of rofecoxib >25 mg were associated with a higher risk than dosages 25 mg. The risk was elevated in the first 90 days of use but not thereafter.
Key Words: cyclooxygenase inhibitors • myocardial infarction • aging
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