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bempedoic acid降低低密度脂蛋白胆固醇的安全性和疗效
Safety and Efficacy of Bempedoic Acid to Reduce LDL Cholesterol


Kausik K. Ray ... 心脑血管疾病 • 2019.03.14
相关阅读
• ACLY和心血管疾病的孟德尔随机化研究 • PCSK9和HMGCR的基因变异与心血管疾病和糖尿病的患病风险

降胆固醇药物治疗的小分子新药

 

张冯筱,黄恺*

华中科技大学同济医学院附属协和医院心血管内科

*通讯作者

 

对于服用最大耐受剂量他汀类药物仍然无法降低胆固醇到合理区间的患者,以依洛尤单抗为代表的PCSK9抑制剂是一种选择。然而其高昂的价格,让不少患者望而却步。2019年3月14日,《新英格兰医学杂志》(NEJM)发表了《bempedoic acid降低低密度脂蛋白胆固醇的安全性和疗效》一文,其结果提示bempedoic acid较好的安全性和疗效,可能为上述患者提供了依洛尤单抗之外的选择。

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摘要


背景

短期研究已经表明,bempedoic acid(ATP柠檬酸裂合酶抑制剂)可降低低密度脂蛋白(LDL)胆固醇水平。在对按照指南建议接受他汀类药物治疗的高胆固醇血症患者开展的长期研究中,bempedoic acid的安全性和疗效数据有限。

 

方法

我们对患动脉粥样硬化性心血管疾病、杂合子型家族性高胆固醇血症或同时患这两种疾病的患者开展了一项随机、对照试验。纳入本试验的患者必须在接受最大耐受剂量他汀类药物治疗(使用或不使用其他降脂疗法)的情况下LDL胆固醇水平至少为70 mg/dL(最大耐受剂量他汀类药物治疗的定义为研究者确定患者可维持的最大强度他汀类药物治疗方案)。以2∶1的比例将患者随机分组,分别接受bempedoic acid或安慰剂治疗。主要终点为安全性,重要的次要终点(重要疗效终点)为52周中的第12周时LDL胆固醇水平的变化百分比。

 

结果

本试验纳入了2,230例患者,其中1,488例被分配接受bempedoic acid治疗,742例被分配接受安慰剂治疗。基线时的平均(±SD)LDL胆固醇水平为103.2 mg/dL±29.4 mg/dL。在干预期间,两组的不良事件(bempedoic acid组1,487例患者中的1,167例[78.5%]和安慰剂组742例患者中的584例[78.7%])和严重不良事件(分别为216例患者[14.5%]和104例患者[14.0%])发生率无显著差异,但bempedoic acid组中导致终止治疗的不良事件(162例 [10.9%] vs. 53例[7.1%])和痛风(18例 [1.2%] vs. 2例[0.3%])发生率均高于安慰剂组。第12周时,bempedoic acid使平均LDL胆固醇水平降低了19.2 mg/dL,相对于基线变化了-16.5%(比较bempedoic acid组与安慰剂组相对于基线变化,差异为-18.1个百分点;95%置信区间,-20.0~-16.1;P<0.001)。不论背景他汀类药物治疗的强度如何,安全性和疗效结果均一致。

 

结论

在这项为期52周的试验中,最大耐受剂量他汀类药物治疗加用bempedoic acid与加用安慰剂相比,未增加全部不良事件的发生率,并且显著降低了LDL胆固醇水平(由Esperion Therapeutics资助;CLEAR Harmony在ClinicalTrials.gov注册号为NCT02666664)。





作者信息

Kausik K. Ray, M.D., M.Phil., Harold E. Bays, M.D., Alberico L. Catapano, Ph.D., Narendra D. Lalwani, Ph.D., M.B.A., LeAnne T. Bloedon, M.S., R.D., Lulu R. Sterling, Ph.D., Paula L. Robinson, M.S., and Christie M. Ballantyne, M.D. for the CLEAR Harmony Trial*
From the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, London (K.K.R.); the Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY (H.E.B.); the University of Milan and Multimedica IRCCS, Milan (A.L.C.); Esperion Therapeutics, Ann Arbor, MI (N.D.L., L.T.B., L.R.S., P.L.R.); and Baylor College of Medicine, Houston (C.M.B.). Address reprint requests to Dr. Ray at the Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care and Public Health, Imperial College London, St. Dunstan’s Rd., London W6 8RP, United Kingdom, or at k.ray@imperial.ac.uk. *A complete list of the investigators in the CLEAR Harmony trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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