Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2005 Mar 17;352(11):1092-102.
doi: 10.1056/NEJMoa050493. Epub 2005 Feb 15.

Cardiovascular Events Associated With Rofecoxib in a Colorectal Adenoma Chemoprevention Trial

Affiliations
Free article
Clinical Trial

Cardiovascular Events Associated With Rofecoxib in a Colorectal Adenoma Chemoprevention Trial

Robert S Bresalier et al. N Engl J Med. .
Free article

Erratum in

  • N Engl J Med. 2006 Jul 13;355(2):221

Abstract

Background: Selective inhibition of cyclooxygenase-2 (COX-2) may be associated with an increased risk of thrombotic events, but only limited long-term data have been available for analysis. We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term, multicenter, randomized, placebo-controlled, double-blind trial designed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas.

Methods: A total of 2586 patients with a history of colorectal adenomas underwent randomization: 1287 were assigned to receive 25 mg of rofecoxib daily, and 1299 to receive placebo. All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee.

Results: A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up (1.50 events per 100 patient-years), as compared with 26 patients in the placebo group during 3327 patient-years of follow-up (0.78 event per 100 patient-years); the corresponding relative risk was 1.92 (95 percent confidence interval, 1.19 to 3.11; P=0.008). The increased relative risk became apparent after 18 months of treatment; during the first 18 months, the event rates were similar in the two groups. The results primarily reflect a greater number of myocardial infarctions and ischemic cerebrovascular events in the rofecoxib group. There was earlier separation (at approximately five months) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure, pulmonary edema, or cardiac failure (hazard ratio for the comparison of the rofecoxib group with the placebo group, 4.61; 95 percent confidence interval, 1.50 to 18.83). Overall and cardiovascular mortality was similar in the two groups.

Conclusions: Among patients with a history of colorectal adenomas, the use of rofecoxib was associated with an increased cardiovascular risk.

Comment in

Similar articles

See all similar articles

Cited by 566 articles

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources

Feedback