Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial
Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial
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DOI：
10.1056/nejmoa050493
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发表时间：
2005-03-17
影响因子：
158.5
通讯作者：
Baron, JA
中科院分区：
文献类型：
--
作者：
Bresalier, RS;Sandler, RS;Baron, JA
背景：选择性抑制环氧合酶-2（考克斯-2）可能与血栓事件风险增加相关，但只有有限的长期数据可供分析。我们报告了一项长期、多中心、随机、安慰剂对照、双盲试验中与选择性考克斯-2抑制剂罗非昔布的使用相关的心血管结局，该试验旨在确定罗非昔布治疗3年对有结直肠腺瘤病史的患者复发大肠肿瘤性息肉风险的影响。1287人被分配接受25毫克的罗非昔布每日，1299人接受安慰剂。所有代表潜在血栓性心血管事件的患者报告的严重不良事件均由外部委员会以盲法进行判定。结果：在3059患者年的随访中，罗非昔布组共有46例患者发生了确认的血栓性事件（1.50起事件/100患者-年），相比之下，安慰剂组在3327患者-年的随访中有26例患者（0.78例事件/100患者-年）;相应的相对风险为1.92（95%置信区间，1.19至3.11; P=0.008）。治疗18个月后，相对风险增加变得明显;在前18个月，两组的事件发生率相似。结果主要反映了罗非昔布组中心肌梗死和缺血性脑血管事件的数量更多。两组之间在未经裁定的治疗报告的充血性心力衰竭、肺水肿或心力衰竭的发生率方面存在较早的分离（大约在5个月时）（罗非昔布组与安慰剂组比较的风险比为4.61; 95%置信区间为1.50 ~ 18.83）。总体和心血管死亡率是相似的，在两个groups.CONCLUSIONS：在有结直肠腺瘤病史的患者中，使用罗非昔布与心血管风险增加相关。
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.