COX-2 Inhibition for Postoperative Analgesia

In their review article, McCrory and Lindahl state that “although . . .animal data suggest that COX-2 inhibition may worsen myocardial performance in the presence of ischemia, there now is evidence that COX-2 inhibition reduces atherosclerosis.” (1) The authors conclude their review by suggesting that “. . .selective COX-2 inhibitors. . .may represent a safer alternative to nonselective NSAIDs in the treatment of postoperative pain.” However, no data is available from large randomized controlled trials to conclusively demonstrate that COX-2 inhibitors, administered for postoperative analgesia or other indications, produce a reduction in cardiovascular or overall serious adverse events in humans. McCrory and Lindahl do not include in their article the recent evidence from two large and widely discussed trials with over 16,000 patients that show the contrary. Analysis of the safety data of the CLASS trial [celecoxib compared to non-COX-2 selective NSAIDs, 8059 patients (2); complete data set not included in the original publication but published later by the Food and Drug Administration (3)] showed that celecoxib had no advantage over non-selective NSAIDs in terms of either cardiovascular events or overall safety. In the VIGOR trial [rofecoxib vs. naproxen, 8076 patients (4)], patients treated with rofecoxib had a relative risk of 2.36 (95% confidence interval [CI], 1.38–4.02; P 0.002) to encounter a thrombotic cardiovascular adverse event, and a relative risk of 1.19 (95% CI, 1.04–1.38; P 0.016) to experience a serious adverse event [complete safety data published by the Food and Drug Administration (5)]. The potential of COX-2 inhibitors to increase cardiovascular risk has subsequently been subject of review in the literature (6,7). On the basis of the best evidence available to date, it would seem reasonable to treat claims that COX-2 inhibitors are safer agents for postoperative analgesia than non-COX-2 selective NSAIDs with caution.