PCSK9抑制剂对动脉粥样硬化性心血管疾病有效性及安全性的meta分析

目的 系统评价PCSK9抑制剂对动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)患者的有效性及安全性。方法 计算机检索PubMed、Embase、Cochrane图书馆和临床试验注册平台Clinical Trails.gov,检索年限从建库至2022年5月。筛选并纳入PCSK9抑制剂治疗ASCVD患者的随机对照试验(randomized controlled trials,RCTs),应用Review Manager 5.4软件对符合标准的RCTs进行meta分析。结果 共纳入10项随机对照试验,共计54 472例患者。有效性分析结果显示:与对照组相比,PCSK9抑制剂可降低ASCVD患者低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平49.26%(95% CI:-54.00~-44.52,P<0.01),并显著降低了其他5项血脂水平;PCSK9抑制剂组动脉粥样硬化斑块体积百分比(percent atheroma volume,PAV)降低1.1%(95%CI:-1.48~-0.73,P<0.01),最小纤维帽厚度(fibrous cap thickness,FCT)增加31.32%(95%CI:15.82~-46.82,P<0.01);PCSK9抑制剂并没有降低心血管死亡风险(RR=0.97,95%CI0.86~1.10,P>0.05),但可降低心肌梗死风险(RR=0.73,95%CI:0.65~0.81,P<0.01)和卒中风险(RR=0.78,95%CI:0.68~0.90,P<0.01)。安全性分析结果显示:PCSK9抑制剂组与对照组严重不良反应事件(serious adverse events,SAEs)发生率相似(RR=0.97,95%CI:0.95~1.00,P>0.05); 注射部位反应,PCSK9抑制剂组较对照组发生率高(RR=1.57,95%CI:1.40~1.76,P<0.01)。而肌痛、神经认知反应、新发糖尿病发生率与对照组相比差异无统计学意义(P>0.05)。结论 PCSK9抑制剂可显著降低LDL-C水平,降低心肌梗死、卒中发生率,无严重不良反应。

Efficacy and safety of PCSK9 inhibitors on atherosclerotic cardiovascular disease: A meta-analysis

Objective To systematically evaluate the efficacy and safety of proprotein convertase subtilisin/kexin type 9(PCSK9) inhibitors on atherosclerotic cardiovascular disease (ASCVD). Methods PubMed, Embase, Cochrane Library and Clinical Trails.gov were subject to the computer retrieval from the data of database construction to May 2022. The randomized controlled trials (RCTs) of PCSK9 inhibitors for ASCVD patients were screened and incorporated, and the meta analysis on conforming RCTs was performed with Review Manager 5.4 software. Results A total of 10 RCTs comprising 54 472 patients were enrolled. Efficacy analysis results showed that PCSK9 inhibitors could reduce the level of low-density lipoprotein cholesterol (LDL-C) by 49.26%(95%CI: -54.00 to -44.52, P<0.01) and significantly reduced the other five lipid levels compared with the control group. Percent atheroma volume (PAV) reduced by 1.1% (95%CI: -1.48 to 0.73, P<0.01) and the minimum fibrous cap thickness (FCT) increased by 31.32%(95%CI: 15.82 to -46.82, P<0.01) in the PCSK9 inhibitors group. PCSK9 inhibitors did not reduce the risk of cardiovascular death (RR=0.97, 95%CI: 0.86 to 1.10, P>0.05), and reduced the risk of myocardial infarction (RR=0.73, 95%CI 0.65 to 0.81, P<0.01) and stroke (RR=0.78, 95%CI 0.68 to 0.90, P<0.01). The incidence of serious adverse events (SAEs) between the PCSK9 inhibitors group and control group was similar (RR=0.97, 95%CI 0.95 to 1.00, P>0.05). The incidence of injection site reaction in the PCSK9 inhibitor group was higher (RR=1.57, 95%CI: 1.40 to 1.76, P<0.01). Differences in myalgia, neurocognitive reaction and incidence new-onset diabetes weren't statistically significant when compared to such indexes in the control group (P>0.05). Conclusion PCSK9 inhibitors is capable of significantly reducing the level of LDL-C, incidence of myocardial infarction and stroke without serious adverse reactions.