Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
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DOI：
10.1056/nejmoa1706444
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发表时间：
2017-09-28
影响因子：
158.5
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背景尽管基于他汀类药物的低密度脂蛋白（LDL）胆固醇水平治疗有效，但患有动脉粥样硬化性血管疾病的患者仍然面临心血管事件的高风险。Anacetrapib对胆固醇酯转移蛋白（CETP）的抑制作用可降低LDL胆固醇水平并增加高密度脂蛋白（HDL）胆固醇水平。然而，其他CETP抑制剂的试验显示了对心血管结局的中性或不良影响。方法我们进行了一项随机、双盲、安慰剂对照试验，涉及30，449例接受强化阿托伐他汀治疗的动脉粥样硬化性血管疾病成人，平均LDL胆固醇水平为61 mg/dl（1.58 mmol/L），平均非HDL胆固醇水平为92 mg/分升（2.38 mmol/L），平均HDL胆固醇水平为40 mg/分升（1.03 mmol/L）。这些患者被分配接受100 mg anacetrapib每日一次（15，225例患者）或匹配的安慰剂（15，224例患者）。主要结果是首次主要冠状动脉事件，包括冠状动脉死亡、心肌梗死或冠状动脉血运重建。在中位4.1年的随访期间，与安慰剂组相比，安塞曲匹组发生主要结果的患者明显较少（15，225例患者中的1640例[ 10.8%] vs. 15，224例患者中的1803例[11.8%];率比，0.91; 95%置信区间，0.85 - 0.97; P = 0.004）。在多个预先规定的亚组中，风险的相对差异相似。在试验中点，安塞曲匹组的HDL胆固醇平均水平比安慰剂组高43 mg/dl（1.12 mmol/L）（相对差异为104%），非HDL胆固醇平均水平低17 mg/dl（0.44 mmol/L），相对差异为-18%。死亡，癌症，或其他严重不良事件的风险没有显着的组间差异。CONCLUSIONSAmong与动脉粥样硬化性血管疾病的患者谁正在接受强化他汀类药物治疗，使用anacetrapib导致的主要冠状动脉事件的发生率低于使用安慰剂。
BACKGROUNDPatients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.METHODSWe conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.RESULTSDuring the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [ 10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P = 0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between group differences in the risk of death, cancer, or other serious adverse events.CONCLUSIONSAmong patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.