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他汀治疗后联合依折麦布在急性冠脉综合征中的作用
Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes


Christopher P. Cannon ... 心脑血管疾病 • 2015.06.18
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摘要


背景

他汀治疗可降低低密度脂蛋白(LDL)胆固醇水平和心血管事件风险。依折麦布是降低肠内胆固醇吸收的非他汀类药物,但我们目前尚不清楚他汀联合依折麦布治疗能否进一步降低心血管事件的发生风险。

 

方法

本研究为双盲、随机研究,纳入18,144例患者,入选者均为发病10天内住院的急性冠脉综合征患者,其中包括接受降脂治疗的LDL胆固醇水平为50~100 mg/dL(1.3~2.6 mmol/L)的患者或未接受降脂治疗的LDL胆固醇水平在50~125 mg/dL(1.3~3.2 mmol/L)的患者。所有患者分为辛伐他汀(40 mg)+依折麦布(10 mg)联合治疗组(辛伐他汀-依折麦布组)和辛伐他汀(40 mg)+安慰剂组(辛伐他汀单药治疗组)进行对照。主要终点为心源性死亡、非致死性心梗、需要再入院治疗的不稳定型心绞痛、冠状动脉血运重建(随机分组≥30天后)和非致死性卒中的复合终点,平均随访时间6年。

 

结果

在研究期间,中位时间加权的平均LDL胆固醇水平在辛伐他汀-依折麦布组是53.7 mg/dL(1.4 mmol/L),而辛伐他汀单药治疗组是69.5 mg/dL(1.8 mmol/L)(P<0.001)。7年主要终点的Kaplan-Meier事件发生率在辛伐他汀-依折麦布组为32.7%,而在辛伐他汀单药治疗组为34.7%(绝对风险差异是2.0百分点;风险比为0.936;95%可信区间为0.89~0.99;P=0.016)。预设的包括肌肉、胆囊、肝脏不良反应及肿瘤在内的发生率在两组间相似。

 

结论

依折麦布与他汀类药物联合应用能够能进一步降低LDL胆固醇水平,改善结局。此外,在原有目标基础上进一步降低LDL胆固醇水平提供了额外获益(由默克[Merck]公司赞助;IMPROVE-IT ClinicalTrials.gov注册号为NCT00202878)。





作者信息

Christopher P. Cannon, M.D., Michael A. Blazing, M.D., Robert P. Giugliano, M.D., Amy McCagg, B.S., Jennifer A. White, M.S., Pierre Theroux, M.D., Harald Darius, M.D., Basil S. Lewis, M.D., Ton Oude Ophuis, M.D., Ph.D., J. Wouter Jukema, M.D., Ph.D., Gaetano M. De Ferrari, M.D., Witold Ruzyllo, M.D., Paul De Lucca, Ph.D., KyungAh Im, Ph.D., Erin A. Bohula, M.D., D.Phil., Craig Reist, Ph.D., Stephen D. Wiviott, M.D., Andrew M. Tershakovec, M.D., M.P.H., Thomas A. Musliner, M.D., Eugene Braunwald, M.D., and Robert M. Califf, M.D., for the IMPROVE-IT Investigators*
From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Brigham and Women’s Hospital, and Harvard Medical School, Boston (C.P.C., R.P.G., A.M., K.I., E.A.B., S.D.W., E.B.); Duke Clinical Research Institute (DCRI), Durham, NC (M.A.B., J.A.W., C.R., R.M.C.); Montreal Heart Institute, Montreal (P.T.); Vivantes Neukölln Medical Center, Berlin (H.D.); Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.); Canisius-Wilhelmina Ziekenhuis, Nijmegen (T.O.O.), and the Netherlands Leiden University Medical Center, Leiden (J.W.J.) — both in the Netherlands; Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy (G.M.D.F.); National Institute of Cardiology, Warsaw, Poland (W.R.); and Merck, Kenilworth, NJ (P.D.L., A.M.T., T.A.M.). Address reprint requests to Dr. Cannon at the Cardiovascular Division, Brigham and Women’s Hospital, 350 Longwood Ave., 1st Fl., Boston, MA 02115, or at cpcannon@partners.org. * A complete list of investigators in the Improved Reduction of Outcomes: Vyto-rin Efficacy International Trial (IMPROVE-IT) is provided in the Supplementary Appendix, available at NEJM.org.

 

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