Coxibs and cardiovascular risk.

J Cotter and Eric Wooltorton highlight the importance of differences in cyclooxygenase 2 (COX-2) selectivity as a potential explanation for the prothrombotic effects of coxibs. However, they neglect important evidence that celecoxib might not share the same cardiovascular (CV) risk as rofecoxib. An increased thrombotic risk with celecoxib has been demonstrated only in the APC (Adenoma Prevention with Celecoxib) study. On the other hand, data from the CLASS trial and a metaanalysis of multiple controlled trials have not uncovered any prothrombotic effect of celecoxib compared with either conventional NSAIDs or placebo. This is consistent with many observational studies that found increased CV risk with both high and low doses of rofecoxib but not with celecoxib. It is noteworthy that the APC trial demonstrated a trend toward increased CV risk of celecoxib among ASA users. Celecoxib might have caused this effect by interference with ASA-induced inactivation of platelet COX-1, which can occur at significantly lower concentrations of celecoxib than are necessary for inhibition of platelet COX-1 activity. This notion does not contradict our previously stated view that ASA might mitigate CV risk associated with coxibs. However, a recent case–control study showed that the risk-modifying effects of ASA were seen only at a low dose but not at a high dose of rofecoxib. We have, therefore, suggested that higher doses of coxibs could also interfere with the anti-inflammatory effects of ASA mediated by COX-2.