Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, PR China.
Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan Province, PR China.
Atherosclerosis. 2021 Jun;326:25-34. doi: 10.1016/j.atherosclerosis.2021.04.008. Epub 2021 May 7.
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 lipid-lowering outcomes.
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.
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.
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.
前蛋白转化酶枯草溶菌素 9 单克隆抗体（PCSK9 mAb）通过控制肝细胞表面 LDL 受体的表达来降低循环中的低密度脂蛋白胆固醇（LDL-C）。本荟萃分析旨在评估 PCSK9 mAb 在临床和降脂方面的疗效。
从建库起至 2020 年 11 月，我们在 PubMed、Embase 和 ClinicalTrials.gov 上检索了比较 PCSK9 mAb 与依折麦布或安慰剂在心血管高危患者中的随机对照试验（RCT）。
共纳入 28 项 RCT，总计 89115 名参与者。与安慰剂相比，PCSK9 mAb 可显著降低主要不良心脏事件（MACEs）的风险（RR 0.83，95%CI 0.79 至 0.88，p<0.00001）。然而，PCSK9 mAb 与依折麦布之间在 MACEs 发生率方面无差异（RR 0.70，95%CI 0.40 至 1.20，p=0.20）。亚组分析显示，PCSK9 mAb 在预防卒中（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）方面并不优于依折麦布。与安慰剂相比，PCSK9 mAb 可显著降低卒中（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）的发生率，但对心血管死亡的风险无影响（RR 0.96，95%CI 0.86 至 1.07，p=0.45）。在降脂疗效方面，PCSK9 mAb 与依折麦布或安慰剂相比，在第 12 周和第 24 周时可显著降低 LDL-C 从基线的百分比变化。
在心血管高危患者中，PCSK9 mAb 可有效降低 MACEs、卒中及心肌梗死的发生风险，与安慰剂相比。然而，在本研究中，PCSK9 mAb 在预防不良心血管事件方面并不优于依折麦布；仍需要进行具有长期随访和以心血管事件为研究终点的 RCT。
