Treatment of osteoarthritis

Objectives: Although cyclooxygenase-2 inhibitors (coxibs) were developed to cause less gastrointestinal hemorrhage than nonselective nonsterodial antiinflammatory drugs (NSAIDs), there has been concern about their cardiovascular safety. The relative risk of acute myocardial infarction (AMI) was studied among users of celecoxib, rofecoxib, and NSAIDs in Medicare beneficiaries with a comprehensive drug benefit. Methods: A matched case-control study was conducted of 54,475 patients 65 years of age or older who received their medications through two 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 were matched to four controls on the basis of age, gender, and the month of index date. A matched logistic regression model was constructed, including indicators for patient demographics, healthcare use, medication use, and cardiovascular risk factors to assess the relative risk of AMI in patients I who used rofecoxib compared with persons taking no NSAID, taking celecoxib, or taking NSAIDs. Results: Current use of rofecoxib was associated with an elevated relative risk of AMI compared with celecoxib (OR 1.14; 95% Cl, 1.05-1.46; P = 0.011), and with no NSAID (OR, 1.14; 95% CI, 1.00-1.31; P = 0.054). The adjusted relative risk of AMI was also elevated,in dose-specific comparasions; rofecoxib less than or equal to25 mg versus celecoxib less than or equal to200 mg (OR 1.21; 95% Cl, 1.01-1.44; P = 0.036) and rofecoxib >25 mg versus celecoxib >200 mg (OR 1.70; 95% Cl, 1.07-2.7 1; P = 1 0.026). The adjusted relative risks of AMI associated with rofecoxib use of I to 30 days (OR, 1.40; 95% CI, 1.12-1.75; P = 0.005) and 31 to 90 days (OR, 1.38; 95% CI, 1.11-1.72; P = 0.003) were higher than >90 days (OR, 0.96; 95% CI, 0.72-1.25; P = 0.8) compared with celecoxib use of similar duration. Celecoxib was not associated with an increased relative risk of AMI in these comparisions. 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 greater than 25 mg were associated with a higher risk than dosages of 25 mg or less. The risk was elevated in the first 90 days of use, but not thereafter.