NEJM：Dalcetrapib对近期有急性冠脉综合征的稳定性冠心病患者的疗效

　　背景  在观察性分析中，较高水平的高密度脂蛋白胆固醇（HDL-C）与冠心病事件的较低危险相关。然而，通过治疗升高的HDL-C水平是否降低心血管危险尚不确定。抑制胆固醇酯转运蛋白（CETP）可使HDL-C水平升高，因此有可能改善心血管转归。

　　方法  我们随机分配15871 例近期有过急性冠脉综合征的患者,除接受最佳可用循证医疗之外，还接受600 mg/d 的CETP 抑制剂dalcetrapib 或安慰剂治疗。主要疗效终点是冠心病所致死亡、非致死性心肌梗死、缺血性卒中、不稳定型心绞痛或心脏停搏复苏的复合。

　　结果  在随机分组时，平均HDL-C水平为42 mg/dl（1.1 mmol/L），平均低密度脂蛋白胆固醇（LDL-C）水平为76 mg/dl（2.0 mmol/L）。在试验过程中，安慰剂组HDL-C水平与基线相比增加了4%～11%，dalcetrapib 组增加了31%～40%。Dalcetrapib 对LDL-C水平影响轻微。患者中位随访期为31 个月。在进行预先规定的中期分析[包括了1135 例主要终点事件（计划总数的71%）]时，独立数据和安全性监察委员会因（试验）无效建议终止试验。与安慰剂相比，dalcetrapib 没有改变主要终点危险（累计事件发生率分别为8.0%和8.3%，dalcetrapib 的风险比1.04，95%可信区间0.93～1.16，P＝0.52），并且对主要终点的各种组分或总死亡率均无显著影响。与安慰剂组相比，dalcetrapib组中位C-反应蛋白水平高出0.2 mg/L，平均收缩压高出0.6 mmHg（两种比较P值均＜0.001）。

　　结论  在近期有过急性冠脉综合征的患者中，dalcetrapib使HDL-C水平增高，但没有降低复发性心血管事件的危险。

Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome

BACKGROUND

In 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.

METHODS

We 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.

RESULTS

At 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<0.001 for both comparisons).

CONCLUSIONS

In patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann–La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)