Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial

被引:1876
作者
Bresalier, RS
Sandler, RS
Quan, H
Bolognese, JA
Oxenius, B
Horgan, K
Lines, C
Riddell, R
Morton, D
Lanas, A
Konstam, MA
Baron, JA
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med & Nutr, Houston, TX 77030 USA
[2] Univ N Carolina, Dept Med, Chapel Hill, NC USA
[3] Merck Res Labs, West Point, PA USA
[4] Mt Sinai Hosp, Dept Pathol, Toronto, ON M5G 1X5, Canada
[5] Univ Birmingham, Dept Surg, Birmingham, W Midlands, England
[6] Clin Univ Hosp, Dept Med, Zaragoza, Spain
[7] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA
[8] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA
[9] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA
关键词
D O I
10.1056/NEJMoa050493
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页码:1092 / 1102
页数:11
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