英克司兰治疗亚洲动脉粥样硬化性心血管疾病患者或高危人群的疗效与安全性:ORION-18研究中国大陆亚组分析  

Efficacy and Safety of Inclisiran in Aisa Atherosclerotic Cardiovascular Disease Patients or High-risk Population:Chinese Mainland Sub-population Analysis of ORION-18 Study

作　　者：霍勇[1] 李勇[2] 韩雅君 丁春华[4] 邢晓春[5] 张雪莲[6] 李建平[1] 徐标[7] 陈纪言[8] HUO Yong;LI Yong;HAN Yajun;DING Chunhua;XING Xiaochun;ZHANG Xuelian;LI Jianping;XU Biao;CHEN Jiyan(Department of Cardiology,Peking University First Hospital,Beijing 100034,China;Department of Cardiology,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Cardiology,Inner Mongolia Autonomous Region People's Hospital,Hohhot 750306,China;Department of Cardiology,Aerospace Center Hospital,Beijing 100089,China;Department of Cardiology,Tianjin Fourth Central Hospital,Tianjin 300000,China;Department of Cardiology,Jilin Province People's Hospital,Changchun 130022,China;Department of Cardiology,Nanjing Drum Tower Hospital,The Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China;Department of Cardiology,Guangdong Provincial People's Hospital,Guangzhou 510080,China)

机构地区：[1]北京大学第一医院心血管内科,北京100034 [2]复旦大学附属华山医院心血管内科,上海200040 [3]内蒙古自治区人民医院心血管内科,呼和浩特750306 [4]航天中心医院心脏医学部,北京100089 [5]天津市第四中心医院心血管内科,天津300000 [6]吉林省人民医院心血管内科,长春130022 [7]南京大学医学院附属鼓楼医院心血管内科,南京210008 [8]广东省人民医院心血管内科,广州510080

出　　处：《中国循环杂志》2025年第2期124-130,共7页Chinese Circulation Journal

摘　　要：目的:ORION-18研究已证实,英克司兰在亚洲动脉粥样硬化性心血管疾病(ASCVD)患者或ASCVD高危人群中可显著降低低密度脂蛋白胆固醇(LDL-C),且安全性良好。本研究旨在进一步评估英克司兰在中国大陆人群中的疗效与安全性。方法:ORION-18研究是一项在亚洲开展的多中心、随机、双盲、安慰剂对照、Ⅲ期临床试验,其中中国大陆亚组包含232例已接受饮食控制和最大耐受剂量他汀类药物治疗(联合或不联合其他降脂治疗)但LDL-C仍升高的ASCVD患者或ASCVD高危受试者,以1:1的比例随机分组(英克司兰组和安慰剂组各116例),在第1天、第90天和第270天分别接受英克司兰300 mg或安慰剂治疗。主要终点为LDL-C从基线至第330天的百分比变化。次要终点包括:LDL-C从第90天至第360天经时间校正的百分比变化和绝对值变化;LDL-C从基线至第330天的绝对值变化;前蛋白转化酶枯草溶菌素9(PCSK9)、总胆固醇、载脂蛋白B(ApoB)、非高密度脂蛋白胆固醇(non-HDL-C)从基线至第330天的百分比变化。其他次要终点包括:第330天达到LDL-C<1.8 mmol/L、LDL-C较基线降低≥50%、达到所处ASCVD风险水平总体降脂目标(LDL-C总体目标值:ASCVD患者<1.4 mmol/L,ASCVD高危人群<1.8 mmol/L)的受试者比例。安全性终点为治疗期间出现的不良事件、实验室检查异常、严重不良事件及其严重程度和其与治疗的相关性。结果:英克司兰组LDL-C从基线至第330天经安慰剂校正的百分比变化为-61.16%,绝对值变化为-1.73 mmol/L;与安慰剂组相比,英克司兰组LDL-C从第90天至第360天经时间校正的百分比变化为-58.51%,绝对值变化为-1.64mmol/L;英克司兰组PCSK9、总胆固醇、ApoB、non-HDL-C从基线至第330天经安慰剂校正的百分比变化分别为-77.44%、-35.65%、-43.43%、-50.90%(P均<0.0001)。第330天时,英克司兰组和安慰剂组分别有79.6%(74/93)和7.8%(6/77)的受试者达到LDL-C<1.8 mmol/L,分别有Objectives:The ORION-18 study has demonstrated that inclisiran can significantly reduce low-density lipoprotein cholesterol(LDL-C)and has good safety in Asian atherosclerotic cardiovascular disease(ASCVD)patients or ASCVD high-risk population.This subgroup analysis aims to further evaluate the efficacy and safety of inclisiran in Chinese mainland population.Methods:ORION-18 study is a multi-center,randomized,double-blind,placebo-controlled,phaseⅢclinical trial among Asian subjects,Chinese mainland subgroup included 232 ASCVD patients or ASCVD high-risk subjects who had already been treated with diet control and maximum tolerated doses of statins treatment(with or without other lipid-lowering treatments)but still had elevated LDL-C levels.Subjects were randomized in a 1:1 ratio to the inclisiran group and the placebo group(n=116 each),and received 300 mg of inclisiran or placebo respectively on day 0,90 and 270.The primary endpoint was the percentage change in LDL-C from baseline to day 330.The secondary endpoints included the time-adjusted percentage change and absolute change in LDL-C from baseline after day 90 and up to day 360,the absolute change in LDL-C from baseline to day 330,and the percentage changes from baseline to day 330 in proprotein convertase subtilisin/kexin type 9(PCSK9),total cholesterol,apolipoprotein B(ApoB),non-high-density lipoprotein cholesterol(non-HDL-C).Other secondary endpoints included the proportion of participants reaching LDL-C levels of<1.8 mmol/L at day 330,the proportion of participants with≥50%LDL-C reduction from baseline to day 330 and the proportion of participants who attained global lipid targets(the LDL-C target was<1.4 mmol/L for ASCVD patients and<1.8 mmol/L for ASCVD highrisk subjects)at day 330.Safety endpoints included adverse events during treatment,aboratory test abnormalities during treatment,serious adverse events,and assessed their severity and relation to treatment.Results:The inclisiran group showed a placebo-corrected percentage change in LDL-C from basel

关 键 词：动脉粥样硬化性心血管疾病 心血管疾病 低密度脂蛋白胆固醇 英克司兰 小干扰核糖核酸 

分 类 号：R54[医药卫生—心血管疾病]