2期和3期研究均显示，PCSK9单克隆抗体Evolocumab (AMG 145)可显著降低低密度脂蛋白胆固醇(LDL-C)水平。日本学者开展了一项3期研究，旨在评估evolocumab联合他汀治疗对高脂血症或混合性血脂异常以及心血管风险高危患者的有效性和安全性。

        患者被随机分为阿托伐他汀5 mg/d或20mg/d两组，治疗4周。随后，患者第二次被随机分为evolocumab140mg(两周一次，Q2W)或420mg(每月一次，QM)或安慰剂治疗(Q2W或QM)组。共同主要终点事件为基线至12周以及平均10周和12周的LDL-C变化百分比(%)。次要终点事件包括其他血脂谱变化和变化的百分比(%)，以及LDL-C达到<70mg/dl的患者比例。记录不良事件和实验室指标。404例患者被随机分为接受试验药物治疗。基线时安慰剂组和evolocumab组患者平均年龄分别为61岁和62岁，女性分别为39%和40%，心血管疾病或外周动脉疾病比例分别为14%和12%，伴188bet在线平台网址 比例分别为51%和47%。

        结果显示，入组时平均LDL-C水平为128 mg/dL，用阿托伐他汀5 和20mg/d治疗后基线LDL-C水平分别为118 mg/dL和94mg/dL。第2次随机化治疗12周时，与安慰剂组相比，evolocumab组的平均LDL-C降低了67%至76%。治疗组间不良事件的发生率相似。不同剂量evolocumab(Q2W或QM)的安全性和有效性相似。

        该研究表明，高风险患者在接受他汀稳定治疗后，evolocumab可显著降低其LDL-C水平并能耐受。

        相关论文近期发表于《美国心脏病学杂志》(AmJ Cardiol)。

        参考文献：ArihiroKiyosue, et al. Published OnlineAmJ Cardiol:October 16, 2015.DOI:http://dx.doi.org/10.1016/j.amjcard.2015.10.021

A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk
Arihiro Kiyosue, MD, PhD 
,
Narimon Honarpour, MD, PhD
,
Christopher Kurtz, MD
,
Allen Xue, PhD
,
Scott M. Wasserman, MD
,
Atsushi Hirayama, MD, PhD
Open Access
DOI: http://dx.doi.org/10.1016/j.amjcard.2015.10.021
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Article Info
Publication History
Published Online:October 16, 2015Accepted:October 9, 2015Received in revised form:October 9, 2015Received:July 24, 2015
Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk.Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM.Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points includedchange and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded.Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes.At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively.Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar.In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated.