PCSK9抑制剂在ASCVD一、二级预防中对脑卒中的预防效果和安全性分析  

Prevention effecacy and safety of PCSK9 inhibitors in stroke in patients with atherosclerotic cardiovascular disease at primary and secondary prevention

作　　者：石叶军 荆玉雷 张晟奕 李超生 程力群[1] Shi Yejun;Jing Yulei;Zhang Shengyi;Li Chaosheng;Cheng Liqun(Department of Neurology,Affiliated Hospital of Jiangnan University,Wuxi 214122,China;Department of Pediatric Surgery,Children's Hospital Affiliated to Jiangnan University(Wuxi Children's Hospital),Wuxi 214023,China)

机构地区：[1]江南大学附属医院神经内科,无锡214122 [2]江南大学附属儿童医院(无锡市儿童医院)儿外科,无锡214023

出　　处：《中华神经医学杂志》2024年第8期806-816,共11页Chinese Journal of Neuromedicine

摘　　要：目的系统评价前蛋白转化酶枯草杆菌蛋白酶9(PCSK9)抑制剂用于动脉粥样硬化性心血管病(ASCVD)的一级预防及二级预防时,对脑卒中的预防作用及安全性。方法应用计算机检索PubMed、Embase、Web of Science、Cochrane图书馆、中国知网、万方数据库中自建库起至2024年3月收录的关于依洛尤单抗、阿利西尤单抗、托莱西单抗或英克司兰(试验组)治疗高脂血症和ASCVD的随机对照试验研究(对照组使用安慰剂或采用常规治疗)。筛选及应用Cochrane文献质量评估工具评估文献质量后提取有效数据,有效性指标包括脑卒中发生率、缺血性脑卒中发生率,安全性指标包括心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应、出血性脑卒中发生率。使用Stata软件对提取数据进行Meta分析,统计风险差异(RD)。结果共纳入20篇文献(21项随机对照试验研究),包含62799例患者。Meta分析显示:一级预防时试验组与对照组患者脑卒中发生率(RD=0.000,95%CI:-0.002~0.003,P=0.905)、缺血性脑卒中发生率(RD=0.001,95%CI:-0.005~0.006,P=0.824)的差异无统计学意义;试验组患者肌酸激酶升高3倍以上发生率低于对照组,差异有统计学意义(RD=-0.005,95%CI:-0.010~0.000,P=0.039)。二级预防时试验组患者脑卒中发生率(RD=-0.004,95%CI:-0.006~-0.002,P<0.001)、缺血性脑卒中发生率(RD=-0.003,95%CI:-0.005~-0.002,P<0.001)低于对照组,差异均有统计学意义;试验组和对照组患者心血管死亡、转氨酶升高3倍以上、肌酸激酶升高3倍以上、过敏反应及出血性脑卒中发生率的差异均无统计学意义(P>0.05)。结论PCSK9抑制剂用于ASCVD的一级预防时,对脑卒中及缺血性脑卒中发生率无显著影响,但能降低肌酸激酶升高3倍以上发生率;用于ASCVD的二级预防时,能有效降低脑卒中和缺血性卒中的发生风险,且不增加并发症的发生率,临床应用具有一定的安全性。ObjectiveTo examine the prevention effecacy and safety of preprotein convertase subtilisin-kexin 9(PCSK9)inhibitors in stroke in patients with atherosclerotic cardiovascular disease(ASCVD)at primary and secondary prevention.MethodsPubMed,Embase,Web of Science,Cochrane Library,and Wanfang and CNKI databases were searched for randomized controlled trials comparing evolocumab,alirocumab,tafolecimab or inclisiran(experimental group)with placebo or conventional therapy(control group)in hyperlipidemia and ASCVD from inception to March 2024.Valid data were extracted after screening and applying Cochrane Literature quality assessment tool to assess the literature quality.Efficacy outcome(incidences of stroke and ischemic stroke)and safety outcome(cardiovascular mortality,and incidences of aminotransferase increased by more than 3 times,creatine kinase increased by more than 3 times,allergic reaction and hemorrhagic stroke)were recorded.Meta analysis of the extracted data was conducted using Stata software to calculate the risk difference(RD).ResultsTwenty articles(21 randomized controlled trials)were included with 62799 patients.For primary prevention,no significant difference was found between PCSK9 inhibitors and control groups in stroke incidence(RD=0.000,95%CI:-0.002-0.003,P=0.905)or ischemic stroke incidence(RD=0.001,95%CI:-0.005-0.006,P=0.824);incidence of creatine kinase increased by more than 3 times in the PCSK9 inhibitors group was significantly decreased compared with that in the control group(RD=-0.005,95%CI:-0.010-0.000,P=0.039).For secondary prevention,PCSK9 inhibitors group had significantly reduced stroke incidence(RD=-0.004,95%CI:-0.006--0.002,P<0.001)and ischemic stroke incidence(RD=-0.003,95%CI:-0.005--0.002,P<0.001)compared with control group;no significant differences in cardiovascular mortality,or incidences of aminotransferase increased by more than 3 times,creatine kinase increased by more than 3 times,allergic reaction and hemorrhagic stroke were noted between the PCSK9 inhibitors group and contr

关 键 词：前蛋白转化酶枯草杆菌蛋白酶9抑制剂 动脉粥样硬化性心血管病 脑卒中 缺血性脑卒中 一级预防 二级预防 

分 类 号：R743.3[医药卫生—神经病学与精神病学]