Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events
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DOI：
10.1056/nejmoa1500858
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发表时间：
2015-04-16
影响因子：
158.5
通讯作者：
Stein, Evan A.
中科院分区：
文献类型：
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作者：
Sabatine, Marc S.;Giugliano, Robert P.;Stein, Evan A.
在短期研究中，一种抑制前蛋白转化酶枯草杆菌蛋白酶-kexin 9型（PCSK 9）的单克隆抗体显著降低了低密度脂蛋白（LDL）胆固醇水平。我们进行了两个扩展研究，以获得长期data.METHODSIn两个开放标签，随机试验，我们招募了4465例患者谁完成了12个2期或3期研究（“母试验”）的evolocumab。无论母试验中的研究组分配如何，符合条件的患者以2：1的比例随机分配接受evolocumab（140 mg每2周一次或420 mg每月一次）加标准治疗或仅接受标准治疗。患者随访中位时间为11.1个月，评估血脂水平、安全性和（作为预先规定的探索性分析）裁定的心血管事件，包括死亡、心肌梗死、不稳定型心绞痛、冠状动脉血运重建、卒中、短暂性脑缺血发作和心力衰竭。将两项试验的数据结合起来，与单独的标准治疗相比，依洛尤单抗使LDL胆固醇水平降低了61%，从中位数120 mg/dl降至48 mg/dl（P
BACKGROUNDEvolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in short-term studies. We conducted two extension studies to obtain longer-term data.METHODSIn two open-label, randomized trials, we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ("parent trials") of evolocumab. Regardless of study-group assignments in the parent trials, eligible patients were randomly assigned in a 2: 1 ratio to receive either evolocumab (140 mg every 2 weeks or 420 mg monthly) plus standard therapy or standard therapy alone. Patients were followed for a median of 11.1 months with assessment of lipid levels, safety, and (as a prespecified exploratory analysis) adjudicated cardiovascular events including death, myocardial infarction, unstable angina, coronary revascularization, stroke, transient ischemic attack, and heart failure. Data from the two trials were combined.RESULTSAs compared with standard therapy alone, evolocumab reduced the level of LDL cholesterol by 61%, from a median of 120 mg per deciliter to 48 mg per deciliter (P