Meta-analysis of randomized clinical trials comparing PCSK9 monoclonal antibody versus ezetimibe/placebo in patients at high cardiovascular risk
Meta-analysis of randomized clinical trials comparing PCSK9 monoclonal antibody versus ezetimibe/placebo in patients at high cardiovascular risk
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DOI：
10.1016/j.atherosclerosis.2021.04.008
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发表时间：
2021-05-15
期刊：
影响因子：
5.3
通讯作者：
Hu, Zhao
中科院分区：
文献类型：
--
作者：
Ma, Wenfang;Guo, Xiying;Hu, Zhao
背景和目标：前蛋白转化酶枯草杆菌蛋白酶/kexin 9型单克隆抗体（PCSK 9 mAb）通过控制肝细胞表面LDL受体的表达来降低循环低密度脂蛋白胆固醇（LDL-C）。该荟萃分析旨在评价PCSK 9 mAb对临床和降脂结局的疗效。方法：检索PubMed、Embase和ClinicalTrials.gov从开始到2020年11月的随机对照试验（RCT），比较PCSK 9 mAb与依折麦布或安慰剂在心血管高风险患者中的作用。结果：共纳入28项RCT，共89，115例受试者。与安慰剂相比，PCSK 9 mAb显著降低了主要不良心脏事件（MACE）的风险（RR 0.83，95% CI 0.79至0.88，p < 0.00001）。然而，PCSK 9 mAb与依折麦布之间发生的MACE无差异（RR 0.70，95% CI 0.40 - 1.20，p = 0.20）。次要分析显示，PCSK 9 mAb在预防卒中方面不优于依折麦布上级（RR 0.38，95% CI 0.09至1.69，p = 0.20）、心肌梗死（RR 0.95，95% CI 0.47至1.90，p = 0.88）和心血管死亡（RR 0.44，95% CI 0.14至1.43，p = 0.17）。与安慰剂相比，PCSK 9 mAb显著降低了卒中的发生率（RR 0.75，95% CI 0.66至0.86，p < 0.0001）和心肌梗死（RR 0.81，95% CI 0.76至0.87，p < 0.00001），但心血管死亡风险不高（RR 0.96，95% CI 0.86至1.07，p = 0.45）。关于降脂疗效，与依折麦布或安慰剂相比，PCSK 9 mAb显著降低了LDL-C自基线至第12周和第24周的百分比变化。结论：在心血管高危患者中，与安慰剂相比，PCSK 9 mAb可有效减少MACE、卒中和心肌梗死。然而，在我们的研究中，PCSK 9 mAb在预防心血管不良事件方面并不上级依折麦布;仍然需要以长期随访和心血管事件作为研究终点的RCT。
Background and aims: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) reduce circulating low-density lipoprotein cholesterol (LDL-C) by controlling the expression of LDL-receptor on the surface of hepatocytes. This meta-analysis aimed at evaluating the efficacy of PCSK9 mAbs on clinical and lipidlowering outcomes. Methods: PubMed, Embase, and ClinicalTrials.gov were searched from inception until November 2020 for randomized controlled trials (RCTs) that compared PCSK9 mAbs with ezetimibe or placebo in patients at high cardiovascular risk. Results: Twenty eight RCTs with a total of 89,115 participants were included. Compared with placebo, PCSK9 mAbs significantly reduced the risk of major adverse cardiac events (MACEs) (RR 0.83, 95% CI 0.79 to 0.88, p < 0.00001). However, no difference was observed in occurring MACEs between PCSK9 mAbs and ezetimibe (RR 0.70, 95% CI 0.40 to 1.20, p = 0.20). Secondary analyses show that PCSK9 mAbs were not superior to ezetimibe in preventing stroke (RR 0.38, 95% CI 0.09 to 1.69, p = 0.20), myocardial infarction (RR 0.95, 95% CI 0.47 to 1.90, p = 0.88), and cardiovascular death (RR 0.44, 95% CI 0.14 to 1.43, p = 0.17). Compared with placebo, PCSK9 mAbs significantly reduced the incidence of stroke (RR 0.75, 95% CI 0.66 to 0.86, p < 0.0001) and myocardial infarction (RR 0.81, 95% CI 0.76 to 0.87, p < 0.00001), but not the risk of cardiovascular death (RR 0.96, 95% CI 0.86 to 1.07, p = 0.45). As for lipid-lowering efficacy, PCSK9 mAbs markedly reduced percent change of LDL-C from baseline to week 12 and 24 compared to ezetimibe or placebo. Conclusions: In patients at high cardiovascular risk, PCSK9 mAbs could effectively reduce MACEs, stroke, and myocardial infarction compared with placebo. However, PCSK9 mAbs were not superior to ezetimibe in preventing adverse cardiovascular events in our study; RCTs with long-term follow-up and cardiovascular events as the research endpoint are still needed.