阿利西尤单抗与依折麦布治疗高胆固醇血症合并心血管高危患者的疗效及安全性比较:ODYSSEY EAST研究中国地区亚组分析  

Efficacy and safety of alirocumab versus ezetimibe in high cardiovascular risk Chinese patients with hyperlipidemia:ODYSSEY EAST Study-Chinese sub-population analysis

作　　者：韩雅玲 马颖艳 苏国海[2] 李毅 李晔 刘东方 宋蓉 李建勇 Han Yaling;Ma Yingyan;Su Guohai;Li Yi;Li Ye;Liu Dongfang;Song Rong;Li Jianyong(Department of Cardiology,General Hospital of Northern War Zone,Shenyang 110016,China;Department of Cardiology,Jinan Central Hospital Affiliated to Shandong University,Jinan 250000,China;Medical,Sanofi(China)Investment Co.,Ltd.Shanghai Branch,Shanghai 200040,China;R&D,Sanofi(China)Investment Co.,Ltd.Shanghai Branch,Shanghai 200040,China)

机构地区：[1]北部战区总医院心内科,沈阳110016 [2]山东省济南市中心医院心内科,250000 [3]赛诺菲(中国)投资有限公司上海分公司医学部,200040 [4]赛诺菲(中国)投资有限公司上海分公司研发部,200040

出　　处：《中华心血管病杂志》2020年第7期593-599,共7页Chinese Journal of Cardiology

摘　　要：目的在已接受最大耐受剂量他汀治疗的高胆固醇血症合并心血管高危的中国患者中,比较阿利西尤单抗[前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂]与依折麦布的疗效及安全性。方法ODYSSEY EAST研究为一项随机、双盲、双模拟、阳性平行对照、多中心临床研究,其中中国亚组包含456例已接受最大耐受剂量他汀治疗的高胆固醇血症合并心血管高危患者,以2∶1的比例随机分组,其中阿利西尤单抗组患者接受阿利西尤单抗皮下注射75 mg每2周1次(Q2W),若第8周低密度脂蛋白胆固醇(LDL-C)≥1.81 mmol/L,则在第12周上调阿利西尤单抗剂量至150 mg Q2W;依折麦布组患者接受依折麦布10 mg/d口服治疗,治疗持续24周。主要疗效指标为LDL-C第24周较基线的变化百分比。关键次要疗效指标包括第12和24周LDL-C(12周)及脂蛋白(a)[Lp(a)]、载脂蛋白A1(Apo A1)、载脂蛋白B(Apo B)、总胆固醇、高密度脂蛋白胆固醇(HDL-C)、非HDL-C、空腹甘油三酯较基线的变化百分比,和第24周达到LDL-C<1.81 mmol/L的患者比例。同时在治疗期间评价治疗药物的安全性。结果456例中国患者年龄(59.5±10.9)岁,男性341例(74.8%),阿利西尤单抗组303例(66.4%),依折麦布组153(33.5%),2组间人口学、临床特征和血脂指标各项基线值差异无统计学意义。在第12和24周,阿利西尤单抗降低LDL-C的幅度均大于依折麦布,较基线变化百分比的均值差分别为(-35.2±2.2)%和(-36.9±2.5)%(P均<0.001)。第12周,阿利西尤单抗组Lp(a)、Apo B、总胆固醇和非HDL-C较基线的降幅比依折麦布组更显著,2组变化百分比的均值差分别为(-40.3±2.8)%,(-27.7±1.8)%,(-19.6±1.5)%和(-27.7±1.9)%(P均<0.001)。第24周,阿利西尤单抗组达到LDL-C<1.81 mmol/L(85.3%比42.2%)和<1.42 mmol/L(70.5%比17.0%)的患者比例显著高于依折麦布组(P均<0.001);且Lp(a)、ApoB、总胆固醇和非HDL-C较基线的降幅也更为显著,2组变化百分比的均值差分别为ObjectiveTo compare the efficacy and safety profile of alirocumab(PCSK9 inhibitor)versus ezetimibe on top of maximally tolerated statin dose in high cardiovascular risk Chinese patients with hyperlipidemia.MethodsThe ODYSSEY EAST study was a randomized,double-blinded,double dummy,active-control,parallel group,multi-centers clinical trial,the Chinese sub-population included 456 patients with hyperlipidemia and high cardiovascular risk on maximally tolerated statin dose.Patients were randomized(2∶1)to receive the subcutaneous injection of alirocumab(75 mg Q2W;with dose up titration to 150 mg Q2W at week 12 if low-density lipoprotein cholesterol(LDL-C)was≥1.81 mmol/L at week 8)or the oral administration of ezetimibe(10 mg daily)for 24 weeks.The primary endpoint was percentage change in calculated LDL-C from baseline to week 24.Key secondary efficacy endpoints included percentage change from baseline to week 12 or 24 in LDL-C(week 12)and other lipid parameters,including apolipoprotein(Apo)B,non-high-density lipoprotein cholesterol(non-HDL-C),TC,lipoprotein(a)(Lp(a)),HDL-C,fasting triglycerides(TG),and Apo A1,and the proportion of patients reaching LDL-C<1.81 mmol/L at week 24.Safety profile of therapeutic drugs was also assessed during the treatment period.ResultsThe mean age of 456 Chinese patients was(59.5±10.9)years,341(74.8%)patients were male,303 patients(66.4%)in alirocumab group and 153 patients(33.5%)in ezetimibe group.Demographic characteristics,disease characteristics,and lipid parameters at baseline were similar between the two groups.LDL-C was reduced more from baseline to week 12 and 24 in alirocumab group versus ezetimibe group,the difference of their least-squares mean(standard error)percent change were(-35.2±2.2)%and(-36.9±2.5)%(both P<0.001).At 12 weeks,alirocumab had significant reduction on Lp(a),Apo B,total cholesterol and non HDL-C,the difference of their least-squares mean(standard error)percent change were(-40.3±2.8)%,(-27.7±1.8)%,(-19.6±1.5)%and(-27.7±1.9)%,respectively(all P<0.001)

关 键 词：高胆固醇血症 心血管疾病 阿利西尤单抗 前蛋白转化酶枯草溶菌素9抑制剂 低密度脂蛋白胆固醇 

分 类 号：R589.2[医药卫生—内分泌] R54[医药卫生—内科学]