Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease
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DOI：
10.1056/nejmoa1609581
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发表时间：
2017-05-18
影响因子：
158.5
通讯作者：
Nissen, Steven E.
中科院分区：
文献类型：
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作者：
Lincoff, A. Michael;Nicholls, Stephen J.;Nissen, Steven E.
背景：胆固醇酯转移蛋白抑制剂evacetrapib可显著提高高密度脂蛋白（HDL）胆固醇水平，降低低密度脂蛋白（LDL）胆固醇水平，增强细胞胆固醇外排能力。我们试图确定evacetrapib对高危血管疾病患者主要不良心血管结局的影响。方法：在一项多中心、随机、双盲、安慰剂对照的3期试验中，我们招募了12092名至少患有以下一种疾病的患者：在过去30至365天内患有急性冠状动脉综合征、脑血管粥样硬化性疾病、外周血管动脉疾病或糖尿病合并冠状动脉疾病。患者被随机分配接受130毫克剂量的evacetrapib或匹配的安慰剂，每天给药，除了标准的药物治疗。主要疗效终点是首次出现心血管原因、心肌梗死、中风、冠状动脉血运重建术或因不稳定心绞痛住院的死亡。结果3个月后，观察到evacetrapib平均LDL胆固醇水平下降31.1%，而安慰剂增加6.0%；平均HDL胆固醇水平上升133.2%，而安慰剂增加1.6%。在计划的1670个主要终点事件中的1363个发生后，数据和安全监测委员会建议由于缺乏疗效而提前终止试验。在使用evacetrapib或安慰剂的中位时间为26个月后，12.9%的evacetrapib组患者和12.8%的安慰剂组患者发生了主要终点事件（风险比为1.01；95%可信区间为0.91至1.11;P = 0.91）。结论：尽管胆固醇酯转移蛋白抑制剂evacetrapib对已建立的脂质生物标志物有良好的影响，但在高危血管疾病患者中，使用evacetrapib治疗并不会导致心血管事件发生率低于安慰剂。（由礼来公司资助；ACCELERATE ClinicalTrials.gov编号：NCT01687998）
BACKGROUNDThe cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.METHODSIn a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.RESULTSAt 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P = 0.91).CONCLUSIONSAlthough the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998.)