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alirocumab与急性冠脉综合征后的心血管结局
Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome


Gregory G. Schwartz ... 心脑血管疾病 • 2018.11.29
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随访时间最长的PCSK9抑制剂试验表明alirocumab带来心血管受益

 

唐熠达

中国医学科学院附属阜外医院

 

2018年11月,PCSK9抑制剂alirocumab临床试验(ODYSSEY-OUTCOMES研究)正式发表于《新英格兰医学杂志》1。这是目前PCSK9抑制剂领域随访时间最长的研究。在长达2.8年的随访期中,研究者观察到alirocumab可将LDL-C目标值控制在25~50 mg/dL,甚至达到15 mg/dL,且较对照组显著减少了MACE、心肌梗死和缺血性卒中,并降低全因死亡,同时安全性和耐受性良好。目前完成临床验证的PCSK9抑制剂共有三种,包括依洛尤单抗、bococizumab,以及此次报道的alirocumab;上述三种药物均显示出强大的降胆固醇药效以及随之而来的心血管系统获益。PCSK9抑制剂成为动脉粥样硬化性疾病及家族性高胆固醇血症的强有利治疗手段。

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摘要


背景

急性冠脉综合征患者发生复发性缺血性心血管事件的风险较高。我们试图确定在接受高强度他汀类药物治疗的患者中,alirocumab(前蛋白转化酶枯草溶菌素-9 [PCSK9]的人单克隆抗体)是否会改善急性冠脉综合征后的心血管结局。

 

方法

我们在1~12个月前罹患急性冠脉综合征,低密度脂蛋白(LDL)胆固醇水平至少为70 mg/dL(1.8 mmol/L)、非高密度脂蛋白胆固醇水平至少为100 mg/dL(2.6 mmol/L)或载脂蛋白B水平至少为80 mg/dL,并且正在接受高强度剂量或最大耐受剂量他汀类药物治疗的18,924例患者中,开展了一项多中心、随机、双盲、安慰剂对照试验。患者被随机分组,接受75 mg剂量的alirocumab(9,462例患者)或匹配安慰剂(9,462例患者)每2周1次皮下给药。在设盲的情况下调整alirocumab剂量,以25~50 mg/dL(0.6~1.3 mmol/L)的LDL胆固醇水平为目标。主要终点是由冠心病死亡、非致死性心肌梗死、致死性或非致死性缺血性卒中或者需要住院的不稳定型心绞痛构成的复合终点。

 

结果

中位随访持续时间为2.8年。alirocumab组903例患者(9.5%)和安慰剂组1,052例患者(11.1%)发生了复合主要终点事件(风险比,0.85;95%置信区间[CI],0.78~0.93;P<0.001)。共有alirocumab组334例患者(3.5%)和安慰剂组392例患者(4.1%)死亡(风险比,0.85;95% CI,0.73~0.98)。在基线LDL胆固醇水平≥100 mg/dL的患者中,alirocumab在复合主要终点方面的绝对获益大于基线水平较低的患者。除了局部注射部位反应(alirocumab组3.8% vs.安慰剂组2.1%)之外,两组的不良事件发生率相似。

 

结论

在既往患急性冠脉综合征并且正在接受高强度他汀类药物治疗的患者中,接受alirocumab治疗患者的复发性缺血性心血管事件风险低于接受安慰剂治疗的患者(由赛诺菲和再生元制药[Regeneron Pharmaceuticals]资助;ODYSSEY OUTCOMES在ClinicalTrials.gov注册号为NCT01663402)。





作者信息

Gregory G. Schwartz, M.D., Ph.D., P. Gabriel Steg, M.D., Michael Szarek, Ph.D., Deepak L. Bhatt, M.D., M.P.H., Vera A. Bittner, M.D., M.S.P.H., Rafael Diaz, M.D., Jay M. Edelberg, M.D., Ph.D., Shaun G. Goodman, M.D., Corinne Hanotin, M.D., Robert A. Harrington, M.D., J. Wouter Jukema, M.D., Ph.D., Guillaume Lecorps, M.Sc., Kenneth W. Mahaffey, M.D., Angèle Moryusef, M.D., Robert Pordy, M.D., Kirby Quintero, R.N., Matthew T. Roe, M.D., M.H.S., William J. Sasiela, Ph.D., Jean-François Tamby, M.D., Pierluigi Tricoci, M.D., M.H.S., Ph.D., Harvey D. White, D.Sc., and Andreas M. Zeiher, M.D. for the ODYSSEY OUTCOMES Committees and Investigators*
From the Division of Cardiology, University of Colorado School of Medicine, Aurora (G.G.S.); Assistance Publique–Hôpitaux de Paris, Hôpital Bichat, Paris Diderot University, Sorbonne Paris Cité, FACT (French Alliance for Cardiovascular Trials), and INSERM Unité 1148 (P.G.S.), and Sanofi (C.H., G.L.) — all in Paris; the National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London (P.G.S.); the State University of New York Downstate School of Public Health, Brooklyn (M.S.), and Regeneron Pharmaceuticals, Tarrytown (R.P., W.J.S.) — both in New York; Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B.); the Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham (V.A.B.); Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Rosario, Argentina (R.D.); Sanofi, Bridgewater, NJ (J.M.E., A.M., J.-F.T.); the Canadian VIGOUR Centre, University of Alberta, Edmonton, and St. Michael’s Hospital, University of Toronto, Toronto — both in Canada (S.G.G.); Stanford Center for Clinical Research, Department of Medicine, Stanford University, Stanford, CA (R.A.H., K.W.M.); the Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands (J.W.J.); Duke Clinical Research Institute, Duke University Medical Center (K.Q., M.T.R., P.T.), and the Division of Cardiology, Department of Medicine, Duke University School of Medicine (M.T.R.), Durham, NC; Green Lane Cardiovascular Services, Auckland City Hospital, Auckland, New Zealand (H.D.W.); and the Department of Medicine III, Goethe University, Frankfurt am Main, Germany (A.M.Z.). Address reprint requests to Dr. Schwartz at the Division of Cardiology, University of Colorado School of Medicine, Box B130, Aurora, CO 80045, or at gregory.schwartz@ucdenver.edu. *A complete list of the ODYSSEY OUTCOMES committee members, investigators, and contributors and their institutional affiliations is provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.

 

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