After the use of rofecoxib was associated with an increased risk of cardiovascular events in the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial, the drug was withdrawn from the worldwide market in 2004. A 1-year period of postdrug observation has already revealed an increased cardiovascular risk even after stopping treatment, therefore the aim of this study was to retrospectively analyse data from one other rofecoxib clinical trial (study 078) to examine how long patients were at increased risk after stopping Vioxx.
Among 1451 patients enrolled in study 078, 723 were assigned to rofecoxib and 728 to placebo. During off-drug follow-up, 22 cardiovascular thromboembolic adverse events occurred among patients on rofecoxib, compared to only six amongst patients on placebo (P=.02). In addition, 23 deaths occurred in rofecoxib-treated subjects compared to 9 amongst patients on placebo (P=.06).
This study found a 100% increased cardiovascular risk associated with rofecoxib use even after discontinuation of the drug. It is currently unknown how long patients may remain at increased risk for, nor the exact mechanism responsible.
- Ross JS, Madigan D, Konstam MA, et al. Persistence of cardiovascular risk after rofecoxib discontinuation. Arch Intern Med 2010; 170:2035-2036.