Sequential safety monitoring of rofecoxib for cardiovascular adverse effects

In 2004, a placebo-controlled trial, Adenomatous Polyp Prevention on Vioxx (APPROVe) was halted due to an increased cardiovascular (CV) risk in patients using rofecoxib. Based on this, Merck voluntarily withdrew rofecoxib from the market in September 2004. However, an estimated number of 80 million people had already taken rofecoxib by the time of its withdrawal. In this methodological study, we performed sequential monitoring of rofecoxib use and CV outcomes using a case-time-control design to investigate how early the association could have been identified if such a monitoring setup were in place.