Kerr DJ et al. (2007) Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer. N Engl J Med 357: 360–369

Inhibition of cyclo-oxygenase 2 might slow the progression of colorectal cancer, but might also increase the risk of adverse cardiovascular events. The cyclo-oxygenase 2 inhibitor rofecoxib was withdrawn worldwide in 2004 after a large trial demonstrated that patients receiving this drug were at an elevated risk of cardiovascular thrombotic events. Kerr et al. have now analyzed data from the VICTOR trial of rofecoxib in patients who had undergone curative surgery for colorectal cancer in order to evaluate the cardiovascular risks associated with the short-term use of this drug to prevent disease recurrence. Patients were randomized to receive either 25 mg/day rofecoxib or placebo.

The VICTOR trial was prematurely stopped after the withdrawal of rofecoxib, with a total of 2,434 patients having been recruited. The median duration of treatment was 7.4 months for the rofecoxib group and 8.2 months in the placebo group. Median durations of follow-up were 33.0 and 33.4 months, respectively. After adjustment for cardiovascular risk factors, the relative risk of a cardiovascular thrombotic event occurring during treatment or within 14 days after termination of treatment was 2.41 (95% CI 0.93–6.26) for the rofecoxib group (16 events) compared with the placebo group (7 events). During the treatment phase and a 2-year follow-up period, the unadjusted relative risk for a cardiovascular thrombotic event was 1.50 (95% CI 0.76–2.94) for the rofecoxib group compared with the placebo group.

The authors conclude that even short-term (<18 months) use of rofecoxib is associated with increased risk for a cardiovascular thrombotic event.