阿利西尤单抗调节血脂和减少心血管事件有效性与安全性的系统评价

Efficacy and safety of alirocumab for regulating blood lipid and reducing cardiovascular events:a systematic review

目的:评价阿利西尤单抗调节血脂和减少心血管事件的有效性与安全性,为其临床应用提供循证参考。方法:计算机检索PubMed、Embase、Cochrane Library、中国知网、维普、万方等数据库,检索时限均为建库至2020年2月,纳入阿利西尤单抗与安慰剂或阳性药物比较的随机对照试验(RCT),筛选文献,提取资料后采用Cochrane系统评价员手册5.1.0提供的偏倚风险评估工具进行质量评价,采用Stata 16.0软件进行Meta分析。结果:纳入23个RCT共26 404例患者。Meta分析结果显示,阿利西尤单抗降低低密度脂蛋白胆固醇(LDL-C)的百分比显著高于安慰剂(WMD=-56.56,95%CI:-60.17^-52.95,P=0.000)和依折麦布(WMD=-31.57,95%CI:-34.15^-28.98,P=0.000);与安慰剂相比,阿利西尤单抗可显著减少主要不良心血管事件(MACE)(RR=0.86,95%CI:0.79~0.93,P=0.000),但与依折麦布(RR=1.03,95%CI:0.62~1.70,P=0.913)相比差异无统计学意义。安全性方面,阿利西尤单抗的总不良反应发生率与安慰剂和依折麦布相比均无统计学差异,全因死亡率均显著低于安慰剂和依折麦布(均P<0.05),仅局部注射部位反应发生率较安慰剂有所增加(P<0.05)。结论:阿利西尤单抗能显著降低LDL-C,并有效减少心血管事件的发生,不良反应轻微可耐受。

Objective:To evaluate the efficacy and safety of alirocumab for regulating blood lipid, reducing cardiovascular events,and providing evidence-based references for the clinical application.Method:Randomized controlled trials(RCTs) about the efficacy and safety of alirocumab versus placebo/positive controls were retrieved from PubMed,Embase,Cochrane Library,CNKI,VIP and Wanfang database from their establishment to February 2020.After literature selection and data extraction,quality assessment of included literature were performed using the bias risk assessment tool provided by the Cochrane System Evaluator Manual 5.1.0.Meta-analysis was performed by Stata 16.0 software.Result:A total of 23 RCTs with 26 404 patients were included.Meta-analysis results showed that the percentage of LDL-C decreased by alirocumab was significantly greater than both the placebo [WMD=-56.56,95%CI:(-60.17,-52.95),P=0.000] and ezetimibe [WMD=-31.57,95%CI:(-34.15,-28.98),P=0.000].Compared with placebo,alirocumab significantly reduced major cardiovascular events(MACE)(RR=0.86,95%CI:0.79-0.93,P=0.000),but the difference was not statistically significant compared to ezetimibe(RR=1.03,95%CI:0.62-1.70,P=0.913).In terms of safety,the incidence of total adverse events in the alirocumab group was not statistically different compared to the placebo and ezetimibe group. However, the all-cause mortality in the alirocumab group was significantly lower than that in the placebo and ezetimibe group(both P<0.05). In contrast, it is just that the local injection-site reaction rate in the alirocumab group was increased compared to placebo with statistically significant difference(P<0.05).Conclusion:Alirocumab can significantly decrease LDL-C and reduce cardiovascular events,and adverse events are mild and tolerable.