• DOI:10.1056/NEJMOA050493
• Corpus ID: 8161299

Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.

@article{Bresalier2005CardiovascularEA,
  title={Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.},
  author={Robert S. Bresalier and Robert S. Sandler and Hui Quan and James A. Bolognese and Bettina Oxenius and Kevin J. Horgan and Christopher R. Lines and Robert H Riddell and Dion G. Morton and {\'A}ngel Lanas and Marvin A. Konstam and John A. Baron},
  journal={The New England journal of medicine},
  year={2005},
  volume={352 11},
  pages={
          1092-102
        }
}

• R. Bresalier, R. Sandler, +9 authors J. Baron
• Published 17 March 2005
• Medicine
• The New England journal of medicine

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.