Adverse Cardiovascular Effects of Rofecoxib
Steven E. Nissen, M.D., Cleveland Clinic Foundation
New England Journal of Medicine 355;2 – July 13, 2006
The recent public disclosure of data from a 12-month extension study of the Adenomatous Polyp Prevention on Vioxx (APPROVe) trial provides new insights into the effect of rofecoxib on cardiovascular events. These new data reveal the full results of both the original study and the extension phase, including data tables and Kaplan–Meier curves. In the original article, the APPROVe investigators reported event rates using an unusual censoring rule in which events were excluded if they occurred more than 14 days after the study drug was stopped. All data in the new report are assessed by a conventional intention-to-treat analysis. This new report also provides analysis that uses several different end points, including the widely used end point of the Antiplatelet Trialists’ Collaboration (APTC) study. The original article included a post hoc hypothesis that curves for confirmed thrombotic events would not begin to diverge until after 18 months of exposure to rofecoxib. However, all intention-to-treat analyses in the newly released report show that the event curves begin to diverge much earlier, generally within four to six months.