Cyclooxygenase-2 inhibitors have been shown in several clinical trials to produce an increased risk of cardiovascular events. In a recent "cross trial safety analysis," researchers evaluated the results of six clinical trials involving celecoxib to compare the risk of cardiovascular events at baseline with those related to three celecoxib regimens.
Solomon and colleagues searched the literature for all randomized, double-blind, placebo-controlled clinical trials using celecoxib for conditions other than arthritis that had a minimum follow-up of three years; four studies met their criteria and two other studies were obtained from unpublished sources. A pooled analysis of the combined data from the six trials included 7,950 patients with a follow-up of 16,070 patient-years. The primary outcome for the statistical analysis was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, and thromboembolic event.
In the analysis based on a given dosage and calculated by individual hazard ratios, the greatest risk (3.1) of cardiovascular events was found for the dosage 400-mg twice daily; an "intermediate risk" (1.8) was attributed to the dosage 200 mg twice daily, and the lowest risk (1.1) was associated with the dosage 400 mg once daily. The total hazard ratio for the primary end point for all dosages combined was 1.6. The researchers also found that patients with the most cardiovascular risk factors at baseline had the greatest risk of celecoxib-induced adverse events.
Andrea Kayyali, MSN, RN
Solomon SD, et al. Circulation 2008;117(16):2104–13.