Cardiovascular Safety of the Cyclooxygenase-2 Selective Inhibitors Parecoxib and Valdecoxib in the Postoperative Setting: An Analysis of Integrated Data

BACKGROUND: Studies of parecoxib, the inactive prodrug of the cyclooxygenase-2 selective inhibitor valdecoxib, and valdecoxib for postoperative pain relief in patients undergoing coronary artery bypass graft surgery revealed an increased risk of cardiovascular (CV) adverse events compared with placebo. We conducted this study to address whether parecoxib and valdecoxib increased CV risk in noncardiac surgery patients. METHODS: A pooled post hoc analysis was conducted using 2 large datasets: 17 controlled trials of parecoxib for noncardiac studies and 32 studies, including the 17 noncardiac parecoxib studies plus 15 studies of valdecoxib. The 32-study dataset provided 95% power to detect a twofold increase in the incidence of CV adverse events assuming a placebo group incidence of 1% (estimated from previous study data), and 69% power to detect a twofold increase from a 0.5% incidence. RESULTS: The incidence of total CV events for the 17 parecoxib studies was 0.44% (13 of 2966) in patients who received parecoxib and 0.37% (7 of 1915) in those receiving placebo (P > 0.20). In the analysis of 32 studies, the incidence of total CV events was 0.40% (21 of 5285) in the parecoxib/valdecoxib group compared with 0.50% (16 of 3226) in the placebo group (P > 0.20). No significant differences in the incidence of total or any individual CV event category were observed between the parecoxib or parecoxib/valdecoxib and placebo groups in the two analyses. When patients were stratified by number of baseline CV risk factors, no significant difference in CV events was detected in parecoxib/valdecoxib patients compared with placebo. CONCLUSIONS: In the largest analysis of the CV risk of cyclooxygenase selective inhibitors or nonsteroidal antiinflammatory drugs for perioperative pain management, parecoxib and valdecoxib were not found to increase the risk of CV adverse events after noncardiac surgery.