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evacetrapib治疗后高危血管疾病患者的心血管结局
Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease


A. Michael Lincoff ... 心脑血管疾病 • 2017.05.18
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• 又一种胆固醇酯转运蛋白抑制剂,但又一次出现阴性试验结果

摘要


背景

胆固醇酯转运蛋白抑制剂evacetrapib可明显提高高密度脂蛋白(HDL)胆固醇水平,降低低密度脂蛋白(LDL)胆固醇水平,并且增加细胞胆固醇外流能力。我们旨在确定evacetrapib对高危血管疾病患者的主要心血管不良结局产生的影响。

 

方法

在一项多中心、随机、双盲、安慰剂对照的3期试验中,我们纳入了12,092例至少有以下一项状况的患者:在既往30~365日发生过急性冠脉综合征、脑血管动脉粥样硬化疾病、外周血管动脉疾病,或者伴有冠状动脉病变的糖尿病。除了标准的药物治疗外,患者被随机分配接受每日130 mg的evacetrapib或对应的安慰剂治疗。主要疗效终点是初次发生复合终点(包括心血管原因死亡、心肌梗死、卒中、冠脉血运重建,或不稳定型心绞痛住院治疗)的任何构成部分。

 

结果

在3个月时,evacetrapib组的平均LDL胆固醇水平降低了31.1%,而安慰剂组却升高了6.0%。evacetrapib组的平均HDL胆固醇水平升高了133.2%,而安慰剂组升高了1.6%。在计划的1,670起主要终点事件发生了1,363起之后,数据和安全监察委员会因缺乏疗效而建议试验提前终止。经过中位26个月的evacetrapib或安慰剂用药之后,evacetrapib组有12.9%的患者发生了主要终点事件,而安慰剂组有12.8%(风险比,1.01;95%置信区间[CI],0.91~0.11;P=0.91)。

 

结论

尽管胆固醇酯转运蛋白抑制剂evacetrapib对既定的脂质生物标志物产生有益作用,但在高危血管疾病患者中,evacetrapib治疗没有产生比安慰剂更低的心血管事件发生率(礼来制药[Eli Lilly]资助;ACCELERATE在ClinicalTrials.gov注册号为NCT01687998)。





作者信息

A. Michael Lincoff, M.D., Stephen J. Nicholls, M.B., B.S., Ph.D., Jeffrey S. Riesmeyer, M.D., Philip J. Barter, M.B., B.S., Ph.D., H. Bryan Brewer, M.D., Keith A.A. Fox, M.B., Ch.B., F.Med.Sci., C. Michael Gibson, M.D., Christopher Granger, M.D., Venu Menon, M.D., Gilles Montalescot, M.D., Ph.D., Daniel Rader, M.D., Alan R. Tall, M.B., B.S., Ellen McErlean, M.S.N., Kathy Wolski, M.P.H., Giacomo Ruotolo, M.D., Ph.D., Burkhard Vangerow, M.D., Govinda Weerakkody, Ph.D., Shaun G. Goodman, M.D., Diego Conde, M.D., Darren K. McGuire, M.D., M.H.Sc., Jose C. Nicolau, M.D., Jose L. Leiva-Pons, M.D., Yves Pesant, M.D., Weimin Li, M.D., David Kandath, M.D., Simon Kouz, M.D., Naeem Tahirkheli, M.D., Denise Mason, B.S.N., and Steven E. Nissen, M.D., for the ACCELERATE Investigators*
From the Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland (A.M.L., V.M., E.M., K.W., D.M., S.E.N.); South Australian Heart and Medical Research Institute, University of Adelaide, Adelaide (S.J.N.), and School of Medical Sciences, University of New South Wales, Sydney (P.J.B.) — both in Australia; Eli Lilly, Indianapolis (J.S.R., G.R., B.V., G.W.); Washington Cardiovascular Associates, Medstar Research Institute, Washington, DC (H.B.B.); Centre for Cardiovascular Science, University of Edinburgh, Edinburgh (K.A.A.F.); Beth Israel Deaconess Medical Center, Boston (C.M.G.); Duke University Medical Center, Durham, NC (C.G.); Université Sorbonne Paris 6, ACTION Study Group, Hôpital Pitié–Salpêtrière, Assistance Publique–Hôpitaux de Paris, Institut de Cardiologie, Paris (G.M.); Penn Heart and Vascular Center, Philadelphia (D.R.); Columbia University, New York (A.R.T.), and Saratoga Cardiology Associates, Saratoga Springs (D.K.) — both in New York; St. Michael’s Hospital, Toronto (S.G.), Recherche Médicale Saint-Jérôme, Saint-Jérôme, QC (Y.P.), and Centre de Santé et de Services Sociaux du Nord de Lanaudière–Centre Hospitalier Régional de Lanaud, Saint-Charles-Borromée, QC (S.K.) — all in Canada; Instituto Cardiovascular de Buenos Aires, Buenos Aires (D.C.); University of Texas Southwestern Medical Center, Dallas (D.K.M.); Heart Institute (InCor)–University of São Paulo Medical School, São Paulo (J.C.N.); Hospital Central Dr. Ignacio Morones Prieto, San Luis Potosi, Mexico (J.L.L.-P.); the First Affiliated Hospital of Harbin Medical University, Harbin, China (W.L.); and South Oklahoma Heart Research, Oklahoma City (N.T.).Address reprint requests to Dr. Lincoff at C5Research, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, or at lincofa@ccf.org.A complete list of investigators in the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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