Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome
Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome
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DOI：
10.1056/nejmoa1206797
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发表时间：
2012-11-29
影响因子：
158.5
通讯作者：
Wright, R. Scott
中科院分区：
文献类型：
--
作者：
Schwartz, Gregory G.;Olsson, Anders G.;Wright, R. Scott
背景：在观察性分析中，较高水平的高密度脂蛋白（HDL）胆固醇与较低的冠心病事件风险相关。然而，提高高密度脂蛋白胆固醇水平是否能治疗性地降低心血管风险仍不确定。抑制胆固醇酯转移蛋白（CETP）可提高高密度脂蛋白胆固醇水平，从而可能改善心血管疾病的预后。方法：我们随机分配15,871例近期有急性冠状动脉综合征的患者接受CETP抑制剂dalcetrapib，剂量为每日600 mg，或安慰剂，以及现有的最佳循证护理。主要疗效终点为冠心病、非致死性心肌梗死、缺血性中风、不稳定型心绞痛或心脏骤停合并复苏导致的死亡。结果随机分组时，平均HDL胆固醇水平为42 mg /分升（1.1 mmol /升），平均低密度脂蛋白胆固醇水平为76 mg /分升（2.0 mmol /升）。在整个试验过程中，安慰剂组的高密度脂蛋白胆固醇水平从基线增加了4%到11%，dalcetrapib组增加了31%到40%。Dalcetrapib对低密度脂蛋白胆固醇水平的影响很小。患者的中位随访时间为31个月。在预先指定的中期分析中，包括1135个主要终点事件（占预计总数的71%），独立数据和安全监测委员会建议因无效而终止试验。与安慰剂相比，dalcetrapib没有改变主要终点的风险（累积事件率分别为8.0%和8.3%；dalcetrapib的风险比为1.04；95%可信区间为0.93至1.16;P = 0.52），对主要终点或总死亡率的任何组成部分都没有显著影响。与安慰剂相比，dalcetrapib组中位c反应蛋白水平升高0.2 mg / l，平均收缩压升高0.6 mm Hg
BACKGROUNDIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.METHODSWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.RESULTSAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P = 0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P