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Previous Volume 357:360-369 July 26, 2007 Number 4 Next

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ABSTRACT

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, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P=0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P=0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes.

Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months' duration. (Current Controlled Trials number, ISRCTN98278138 [controlled-trials.com] .)

Source Information

From the Oncology Clinical Trials Office, University of Oxford, Oxford (D.J.K., J.L.S., R.S.J.M., J.C.S., P.J., C.I., R.D.); the Statistical Centre at Warwick Medical School Clinical Trials Unit, University of Warwick, Coventry (J.A.D., M.J.L., C.C.M.); and City Hospital, Birmingham (A.S.) — all in the United Kingdom.

Address reprint requests to Dr. Kerr at the Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Woodstock Rd., Oxford OX2 6HA, United Kingdom, or at david.kerr{at}clinpharm.ox.ac.uk.

Full Text of this Article

This article has been cited by other articles:

• Psaty, B. M., Kronmal, R. A. (2008). Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment: A Case Study Based on Documents From Rofecoxib Litigation. JAMA 299: 1813-1817 [Abstract] [Full Text]  
• (2007). Again, Vioxx Is Shown to Increase Cardiovascular Risk. Journal Watch Cardiology 2007: 4-4 [Full Text]  
• (2007). Coxibs, Colorectal Cancer, and Cardiac Risk. JWatch Gastroenterology 2007: 1-1 [Full Text]