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evinacumab治疗难治性高胆固醇血症
Evinacumab in Patients with Refractory Hypercholesterolemia


Robert S. Rosenson ... 心脑血管疾病 • 2020.12.10
相关阅读
• evinacumab治疗纯合子家族性高胆固醇血症 • ANGPTL3的遗传学和药理学失活与心血管疾病

摘要


背景

以最大耐受剂量接受降脂治疗的情况下低密度脂蛋白(LDL)胆固醇水平仍较高的难治性高胆固醇血症患者发生动脉粥样硬化的风险增加。evinacumab是抗血管生成素样3蛋白的全人源性单克隆抗体,目前尚不知晓皮下给药和静脉给药的evinacumab对上述患者的疗效和安全性。

 

方法

在这项双盲、安慰剂对照的2期试验中,我们纳入了符合以下标准的患者:患或未患杂合子家族性高胆固醇血症,患难治性高胆固醇血症,并且筛查时的LDL胆固醇水平≥70 mg/dL(合并动脉粥样硬化的情况下)或≥100 mg/dL(未合并动脉粥样硬化的情况下)。患者被随机分配接受皮下给药或静脉给药的evinacumab或安慰剂。主要终点是evinacumab与安慰剂相比,第16周时的LDL胆固醇水平相对于基线的变化百分比。

 

结果

共计272例患者被随机分配到以下各组:每周450 mg(40例患者)、每周300 mg(43例患者)或每2周300 mg(39例患者)evinacumab或安慰剂(41例患者)皮下给药;或者每4周每千克体重15 mg(39例患者)或每4周每千克体重5 mg(36例患者)evinacumab或安慰剂(34例患者)静脉给药。第16周时,在每周450 mg、每周300 mg或每2周300 mg evinacumab皮下给药组中,LDL胆固醇水平相对于基线的最小二乘均值变化与安慰剂组之间的差异分别为-56.0、-52.9和-38.5个百分点(所有比较的P<0.001)。在15 mg/kg或5 mg/kg evinacumab静脉给药组与安慰剂组之间的差异分别为-50.5个百分点(P<0.001)和-24.2个百分点。各组在治疗期间的严重不良事件发生率为3%~16%。

 

结论

在难治性高胆固醇血症患者中,evinacumab显著降低了LDL胆固醇水平,最大剂量下可降低50%以上(由再生元制药[Regeneron Pharmaceuticals]资助,在ClinicalTrials.gov注册号为NCT03175367)。





作者信息

Robert S. Rosenson, M.D., Lesley J. Burgess, M.D., Ph.D., Christoph F. Ebenbichler, M.D., Seth J. Baum, M.D., Erik S.G. Stroes, M.D., Ph.D., Shazia Ali, Pharm.D., Nagwa Khilla, M.S., Robert Hamlin, B.S., Robert Pordy, M.D., Yuping Dong, Ph.D., Vladimir Son, Ph.D., and Daniel Gaudet, M.D., Ph.D.
From the Icahn School of Medicine at Mount Sinai, New York (R.S.R.), and Regeneron Pharmaceuticals, Tarrytown (S.A., N.K., R.H., R.P., Y.D., V.S.) — both in New York; TREAD Research, Cardiology Unit, Department of Internal Medicine and Tygerberg Hospital, Parow, South Africa (L.J.B.); the Department of Internal Medicine I, Medical University Innsbruck, Innsbruck, Austria (C.F.E.); Excel Medical Clinical Trials, Department of Integrated Medical Sciences, Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton (S.J.B.); the Department of Vascular Medicine, Academic Medical Center, Amsterdam (E.S.G.S.); and the Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine, Université de Montréal Community Gene Medicine Center, Montreal, and ECOGENE-21 Clinical and Translational Research Center, Chicoutimi, QC — both in Canada (D.G.). Address reprint requests to Dr. Rosenson at Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., MC Level, New York, NY 10029.

 

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