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高危患者使用bococizumab的心血管疗效和安全性
Cardiovascular Efficacy and Safety of bococizumab in High-Risk Patients


Paul M Ridker ... 心脑血管疾病 • 2017.04.20
相关阅读
• 通过抑制PCSK9减少心血管事件 • bococizumab降脂效果的变异性和抗药抗体的产生

摘要


背景

bococizumab是一种人源化单克隆抗体,可抑制前蛋白转化酶枯草溶菌素9(PCSK9)和降低低密度脂蛋白(LDL)胆固醇的水平。本研究旨在对心血管高危患者使用bococizumab的疗效进行评估。

 

方法

在两项对LDL胆固醇水平有不同入选标准的平行、多国试验中,两项试验一共有27,438例患者随机分配到bococizumab治疗组和安慰剂组,治疗组每2周一次皮下注射150 mg bococizumab。主要终点是非致死性心肌梗死、非致死性卒中、因需要紧急血运重建的不稳定型心绞痛而住院治疗或者心血管性死亡。基线时93%的患者正在接受他汀治疗。正如研究项目中其他数据所显示的,这两项试验中抗药抗体的产生比例较高,申办方一定程度上由于该原因决定终止bococizumab研发,因此这两项试验也提前终止。整个试验的中位随访时间是10个月。

 

结果

在14周时,在合并的试验中,bococizumab治疗组患者的LDL胆固醇水平较基线的平均变化为-56.0%,而安慰剂组为+2.9%,组间差异达到-59.0个百分点(P<0.001),较基线的中位降幅为64.2%(P<0.001)。在对较低危患者进行的较短期试验中,患者基线LDL胆固醇水平≥70 mg/dL(1.8 mmol/L),中位随访时间为7个月;bococizumab治疗组和安慰剂组均有173位患者发生了主要不良心血管事件(风险比,0.99;95%置信区间[CI],0.80~1.22;P=0.94)。在对较高危患者进行的持续时间较长的试验中(患者基线LDL胆固醇水平≥100 mg/dL [2.6 mmol/L],中位随访时间为12个月),bococizumab治疗组和安慰剂组分别有179例和224例患者发生了主要不良心血管事件(风险比,0.79;95% CI,0.65~0.97;P=0.02)。在合并的试验中,主要终点的风险比为0.88(95% CI,0.76~1.02;P=0.08)。bococizumab治疗组注射部位反应比安慰剂组更加常见(10.4%对1.3%;P<0.001)。

 

结论

在这两项比较PCSK9抑制剂bococizumab和安慰剂的随机试验中,在较低危患者中bococizumab治疗未能在主要心血管不良事件方面带来益处,但是在较高危患者中则产生了显著益处(由辉瑞公司[Pfizer]资助,SPIRE-1和SPIRE-2在ClinicalTrials.gov注册号为NCT01975376和NCT01975389)。





作者信息

Paul M Ridker, M.D., James Revkin, M.D., Pierre Amarenco, M.D., Robert Brunell, Ph.D., Madelyn Curto, D.V.M., Fernando Civeira, M.D., Marcus Flather, M.D., Robert J. Glynn, Sc.D., Jean Gregoire, M.D., J. Wouter Jukema, M.D., Yuri Karpov, M.D., John J.P. Kastelein, M.D., Wolfgang Koenig, M.D., Alberto Lorenzatti, M.D., Pravin Manga, M.D., Urszula Masiukiewicz, M.D., Michael Miller, M.D., Arend Mosterd, M.D., Jan Murin, M.D., Jose C. Nicolau, M.D., Steven Nissen, M.D., Piotr Ponikowski, M.D., Raul D. Santos, M.D., Pamela F. Schwartz, Ph.D., Handrean Soran, M.D., Harvey White, M.D., R. Scott Wright, M.D., Michal Vrablik, M.D., Carla Yunis, M.D., Charles L. Shear, Dr.P.H., and Jean-Claude Tardif, M.D., for the SPIRE Cardiovascular Outcome Investigators*
From Brigham and Women’s Hospital and Harvard Medical School, Boston (P.M.R., R.J.G.); Pfizer, New York (J.R., R.B., M.C., U.M., P.F.S., C.Y., C.L.S.); Paris-Diderot, Sorbonne Paris Cité University, Paris (P.A.); Universidad de Zaragoza, IIS Aragon, Zaragoza, Spain (F.C.); University of East Anglia, Norwich (M.F.), and Central Manchester University Hospital, Manchester (H.S.) — both in the United Kingdom; the Montreal Heart Institute, Université de Montréal, Montreal (J.G., J.-C.T.); Leiden University Medical Center, Leiden (J.W.J.), Academic Medical Center of the University of Amsterdam, Amsterdam (J.J.P.K.), and Meander Medical Center, Amersfoort (A.M.) — all in the Netherlands; Russian Cardiology Research and Production Center, Moscow (Y.K.); Deutsches Herzzentrum München, Technische Universität München, Munich Heart Alliance, Munich, Germany (W.K.); Cordoba Hospital, Cordoba, Argentina (A.L.); University of the Witwatersrand, Johannesburg (P.M.); University of Maryland, Baltimore (M.M.); University of Comenius, Bratislava, Slovakia (J.M.); Heart Institute, University of São Paulo Medical School (J.C.N.), and Lipid Clinic Heart Institute, University of São Paulo Medical School Hospital (R.D.S.), São Paulo; Cleveland Clinic Foundation, Cleveland (S.N.); Wroclaw Medical University, Wroclaw, Poland (P.P.); Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand (H.W.); Mayo Clinic, Rochester, MN (R.S.W.); and First Faculty of Medicine, Charles University, Prague, Czech Republic (M.V.). Address reprint requests to Dr. Ridker at the Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Ave., Boston, MA 02215, or at pridker@partners.org. *A complete list of the Studies of PCSK9 Inhibition and the Reduction of Vascular Events (SPIRE) Cardiovascular Outcome Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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