The purpose of the study was to evaluate the cardiovascular safety of celecoxib compared with placebo and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs).
A meta-analysis was carried out on 41 clinical trials involving 44,300 patients. Inclusion criteria were: randomized parallel-group design; at least 1 treatment group receiving celecoxib ≥ 200 mg total daily dose (TDD); at least 1 placebo, NSAID (ibuprofen, naproxen, or diclofenac at the recommended dose for osteoarthritis and rheumatoid arthritis), or rofecoxib comparator group; planned duration of ≥ 2 weeks; and study completed and report finalized by October 31, 2004. Cardiovascular end points of the study included nonfatal myocardial infarction, nonfatal stroke, CV death, and the Anti-Platelet Trialists’ Collaboration (APTC)-like composite end point (sum of above individual events). Cardiovascular risk associated with all patients receiving celecoxib ≥ 200 mg TDD was compared to patients receiving placebo or NSAIDs. The difference in cardiovascular incidence between the celecoxib, NSAID and placebo group was analysed using the Cochran-Mantel-Haenszel test.Researchers found that in studies comparing celecoxib (50-800 mg TDD; n = 8405) with placebo, 31% of patients were treated ≥ 12 weeks, 3% were treated ≥ 24 weeks, 3% were treated ≥ 36 weeks, and 2% were treated ≥ 52 weeks. In studies comparing celecoxib (50-800 mg TDD; n = 20,463) with NSAIDs, 55% of patients were treated ≥ 12 weeks, 15% were treated ≥ 24 weeks, 12% were treated ≥ 36 weeks, and 4% were treated ≥ 52 weeks. The relative risk for the APTC-like composite end point was not significantly different between the celecoxib ≥ 200 mg TDD and placebo groups or between the celecoxib and NSAID groups (Table). There were no significant differences in relative risk for nonfatal myocardial infection, nonfatal stroke, or cardiovascular death for the celecoxib vs placebo comparison. The incidence of nonfatal myocardial infarction was numerically higher with celecoxib compared with NSAIDs, and the incidence of nonfatal stroke was significantly smaller with celecoxib compared with NSAIDs.Researchers concluded that regardless of exposure length, celecoxib was not associated with an increased risk of serious cardiovascular thromboembolic events compared with placebo or NSAIDs.