Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention
Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention
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DOI：
10.1056/nejmoa050405
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发表时间：
2005-03-17
影响因子：
158.5
通讯作者：
Bertagnolli, M
中科院分区：
文献类型：
--
作者：
Solomon, SD;McMurray, JJV;Bertagnolli, M
背景：选择性环氧合酶-2（考克斯-2）抑制剂已受到审查，因为有报告表明其使用相关的心血管风险增加。实验研究表明，这些药物可能有助于血栓前状态提供了支持这种concerns.METHODS：我们回顾了所有潜在的严重的心血管事件在2035例患者的历史，结直肠肿瘤谁参加了一项试验，比较两种剂量的塞来昔布（200毫克或400毫克，每天两次）与安慰剂预防结直肠腺瘤。所有的死亡被归类为心血管或非心血管，非致命性心血管事件被归类为一个盲目的方式根据预先指定scheme.RESULTS：对于所有患者，除了那些谁死了，2.8至3.1年的随访数据。安慰剂组679例患者中有7例达到了心血管原因、心肌梗死、中风或心力衰竭导致的复合心血管终点死亡（1.0%），相比之下，685例接受200 mg塞来昔布每日两次的患者中有16例（2.3%;风险比，2.3; 95%置信区间，0.9至5.5），671例患者中有23例接受400 mg塞来昔布每日两次治疗（3.4%;风险比，3.4; 95%置信区间，1.4至7.8）。其他复合终点也观察到类似趋势。根据这些观察结果，数据和安全监测委员会建议提前终止研究drug.CONCLUSIONS：塞来昔布的使用与剂量相关的增加，在复合终点的心血管原因，心肌梗死，中风，或心力衰竭死亡。鉴于最近报告了与该类其他药物治疗相关的心血管损害，这些数据提供了进一步证据，证明使用考克斯-2抑制剂可能增加严重心血管事件的风险。
BACKGROUND:Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern.METHODS:We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme.RESULTS:For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug.CONCLUSIONS:Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events.