Rofecoxib and Cardiovascular Adverse Events in Adjuvant Treatment of Colorectal Cancer

作者：David J. Kerr, Janet Dunn, M. J. S. Langman, Justine L. Smith, Rachel Midgley, Andrew Stanley, Joanne C. Stokes, Patrick Julier, Claire Iveson, Ravi Duvvuri, Christopher C. McConkey · 发表于：New England Journal of Medicine · 年份：2007 · DOI：10.1056/nejmoa071841 · 被引用次数：134 · 研究领域：Inflammatory mediators and NSAID effects、Cancer, Stress, Anesthesia, and Immune Response、Chemotherapy-induced cardiotoxicity and mitigation

BACKGROUND: Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. METHODS: All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. RESULTS: The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P=0.04). Analysis of the Antiplatelet Trialists' Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagi...