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利伐沙班或阿司匹林用于静脉血栓栓塞延长治疗的研究
Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism


Jeffrey I. Weitz ... 心脑血管疾病 呼吸系统疾病 • 2017.03.30
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中国应在新型抗凝药革命中扮演何种角色

 

郑哲

北京阜外心血管病医院心外科

 

华法林曾经是静脉血栓栓塞性疾病(venous thromboembolism,VTE)长期二级预防的基石1。由于口服华法林需要监测国际标准化比值(International Normalized Ratio,INR)、调整药量且面临较高的出血风险,因此国际医学界不断探索着更加安全、有效、便利的VTE二级预防策略。但早期研究显示,小剂量华法林效果不佳2;阿司匹林尽管提高用药便利性,降低出血风险,但每年5.1%的血栓事件发生率仍不理想3。新型口服抗凝药(new oral anticoagulants,NOAC)不需要持续监测INR和调整剂量,业已在房颤患者的卒中预防4和VTE早期预防中大显身手5,有望替代阿司匹林和华法林成为VTE长期二级预防的一线药物。

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摘要


背景

虽然很多静脉血栓栓塞患者需要延长治疗,但目前尚未确定全强度抗凝、低强度抗凝或阿司匹林哪种疗法更好。

 

方法

在此项随机、双盲、3期临床试验中,我们将3,396例静脉血栓栓塞患者分配到接受每日1次的利伐沙班(20 mg或10 mg)或100 mg阿司匹林治疗。入组前,所有患者均已完成了6~12个月的抗凝治疗,并且在对于继续抗凝的需求方面符合临床均势原则。研究给药时间最长12个月。主要有效性结局是有症状的、复发的致死性或非致死性静脉血栓栓塞,主要安全性结局是大出血。

 

结果

共有3,365例患者被纳入了意向治疗分析(中位治疗时间为351日)。利伐沙班20 mg组的1,107例患者中的17例(1.5%)患者、利伐沙班10 mg组的1,127例患者中的13例(1.2%)和阿司匹林组的1,131例患者中的50例(4.4%)发生了主要有效性结局(利伐沙班20 mg对阿司匹林的风险比为0.34,95%置信区间[CI]为0.20~0.59;利伐沙班10 mg对阿司匹林的风险比为0.26,95% CI为0.14~0.47;两项比较P<0.001)。利伐沙班20 mg组、利伐沙班10 mg组和阿司匹林组的大出血事件发生率分别为0.5%、0.4%和0.3%;临床相关的非大出血事件发生率分别为2.7%、2.0%和1.8%。三组的不良事件发生率相似。

 

结论

在继续抗凝方面符合临床均势原则的静脉血栓栓塞患者中,治疗剂量(20 mg)或预防剂量(10 mg)的利伐沙班在事件复发的风险方面均显著低于阿司匹林,而且出血发生率未见显著升高(由拜耳制药公司[Bayer Pharmaceuticals]资助;EINSTEIN CHOICE在ClinicalTrials.gov注册号为NCT02064439)。





作者信息

Jeffrey I. Weitz, M.D., Anthonie W.A. Lensing, M.D., Ph.D., Martin H. Prins, M.D., Ph.D., Rupert Bauersachs, M.D., Jan Beyer-Westendorf, M.D., Henri Bounameaux, M.D., Timothy A. Brighton, M.D., Alexander T. Cohen, M.D., Bruce L. Davidson, M.D., M.P.H., Hervé Decousus, M.D., Maria C.S. Freitas, M.D., Ph.D., Gerlind Holberg, V.D., Ph.D., Ajay K. Kakkar, M.B., B.S., Ph.D., Lloyd Haskell, M.D., Bonno van Bellen, M.D., Akos F. Pap, M.Sc., Scott D. Berkowitz, M.D., Peter Verhamme, M.D., Philip S. Wells, M.D., and Paolo Prandoni, M.D., Ph.D., for the EINSTEIN CHOICE Investigators*
From the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON (J.I.W.), and the Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa (P.S.W.) — both in Canada; Bayer Pharmaceuticals, Leverkusen (A.W.A.L., M.C.S.F., G.H., A.F.P., S.D.B.), Vascular Medicine, Klinikum Darmstadt, Darmstadt (R.B.), the Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz (R.B.), and the Department of Hematology, Medical Clinic I, University Hospital Carl Gustav Carus, Dresden (J.B.-W.) — all in Germany; the Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands (M.H.P.); the Division of Angiology and Hemostasis and the Faculty of Medicine, University of Geneva, Geneva (H.B.); the Department of Haematology, Prince of Wales Hospital, Sydney (T.A.B.); the Department of Haematology and Oncology, King’s College London (J.B.-W.), the Department of Haematological Medicine, Guy’s and St. Thomas’ Hospitals, King’s College Hospital (A.T.C.), and Thrombosis Research Institute and University College London (A.K.K.) — all in London; the University of Washington School of Medicine, Seattle (B.L.D.); Centre d’Investigation Clinique 1408, Sainbiose U1059, Investigation Network on Venous Thromboembolism, Service de Médecine Vasculaire et Thérapeutique, Centre Hospitalo-Universitaire, Hôpital Nord, Saint Etienne, France (H.D.); Janssen Research and Development, Raritan, NJ (L.H.); Hospital Beneficência Portuguesa, São Paulo (B.B.); Vascular Medicine and Hemostasis, University of Leuven, Leuven, Belgium (P.V.); and the Department of Cardiothoracic and Vascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy (P.P.). Address reprint requests to Dr. Weitz at the Thrombosis and Atherosclerosis Research Institute, 237 Barton St. E., Hamilton, ON L8L 2X2, Canada, or at weitzj@taari.ca. *A list of the Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN CHOICE) investigators and collaborators is provided in the Supplementary Appendix, available at NEJM.org.

 

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