COX-2 Inhibitors — Lessons in Drug Safety

Approximately six years after the cyclooxygenase-2 (COX-2) inhibitors were approved for use in the United States, the results of three randomized, placebo-controlled trials provide new evidence about the cardiovascular risks of rofecoxib, celecoxib, and valdecoxib.13 The Adenomatous Polyp Prevention on Vioxx (APPROVe) trial, a study of patients with a history of colorectal adenomas, was stopped early because rofecoxib doubled the risk of major cardiovascular events (relative risk, 1.92; 95 percent confidence interval, 1.19 to 3.11). These findings confirmed the increased risk of myocardial infarction previously seen in the Vioxx Gastrointestinal Outcomes Research (VIGOR) trial4 and some observational studies.5 The . . .