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依度沙班治疗癌症相关静脉血栓栓塞
Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism


Gary E. Raskob ... 心脑血管疾病 肿瘤 • 2018.02.15
相关阅读
• 口服直接抗凝剂与使用华法林治疗静脉血栓栓塞的安全性比较 • 在新近诊断为癌症的患者中,动脉血栓栓塞有多常见

摘要


背景

低分子量肝素是癌症相关静脉血栓栓塞的标准治疗方法。口服直接抗凝剂的作用尚不明确。

 

方法

在这项开放标签的非劣效性试验中,我们将患急性有症状或偶发性静脉血栓栓塞的癌症患者随机分配到以下治疗组:接受低分子量肝素至少5日,之后每日1次口服60 mg依度沙班(依度沙班组);或接受200 IU/kg达肝素每日1次皮下给药1个月,之后将达肝素剂量变更为每日1次150 IU/kg(达肝素组)。治疗持续时间最短6个月,最长12个月。主要结局为随机分组后12个月内(无论治疗持续时间如何),复发性静脉血栓栓塞或大出血构成的复合结局。

 

结果

在随机分组的1,050例患者中,1,046例被纳入改良意向性治疗分析。依度沙班组的522例患者和达肝素组的524例患者中,分别有67例(12.8%)和71例(13.5%)发生了主要结局事件(风险比,0.97;95%置信区间[CI],0.70~1.36;非劣效性P=0.006;优效性P=0.87)。依度沙班组和达肝素组分别有41例(7.9%)和59例(11.3%)患者发生了复发性静脉血栓栓塞(风险差异,-3.4个百分点;95% CI,-7.0~0.2)。依度沙班组和达肝素组分别有36例(6.9%)和21例(4.0%)患者发生大出血(风险差异,2.9个百分点,95% CI,0.1~5.6)。

 

结论

在复发性静脉血栓栓塞或大出血构成的复合结局方面,口服依度沙班不劣于达肝素皮下给药。与达肝素组相比,依度沙班组的复发性静脉血栓栓塞发生率较低,但大出血发生率较高(由第一三共株式会社[Daiichi Sankyo]资助;Hokusai VTE Cancer在ClinicalTrials.gov注册号为NCT02073682)。





作者信息

Gary E. Raskob, Ph.D., Nick van Es, M.D., Peter Verhamme, M.D., Marc Carrier, M.D., Marcello Di Nisio, M.D., David Garcia, M.D., Michael A. Grosso, M.D., Ajay K. Kakkar, M.B., B.S., Michael J. Kovacs, M.D., Michele F. Mercuri, M.D., Guy Meyer, M.D., Annelise Segers, M.D., et al., for the Hokusai VTE Cancer Investigators*
From the University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City (G.E.R.); the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (N.E., H.R.B.), and ITREAS, Academic Research Organization (A.S.) — both in Amsterdam; the Department of Vascular Medicine and Hemostasis, University Hospitals Leuven, Leuven, Belgium (P.V.); Ottawa Hospital Research Institute, Ottawa (M.C.), London Health Sciences Centre–Victoria Hospital, London, ON (M.J.K.), University Health Network, University of Toronto, Toronto (E.Y.), and McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, ON (J.I.W.) — all in Canada; the Department of Medicine and Aging Sciences, University G. D’Annunzio, Chieti, Italy (M.D.N.); the Department of Medicine, Division of Hematology, University of Washington, Seattle (D.G.); Daiichi Sankyo Pharma Development, Basking Ridge, NJ (M.A.G., M.F.M., M.S., G.Z.); Thrombosis Research Institute and University College London, London (A.K.K.); the Department of Respiratory Disease, Hôpital Européen Georges-Pompidou, Assistance Publique–Hôpitaux de Paris, Paris (G.M.); the Department of Internal Medicine, Division of Hematology, Ohio State University Wexner Medical Center, Columbus (T.-F.W.); and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (J.I.Z.). Address reprint requests to Dr. Raskob at the University of Oklahoma Health Sciences Center, College of Public Health, 801 NE 13th St., Oklahoma City, OK 73104, or at gary-raskob@ouhsc.edu. *A complete list of Hokusai VTE Cancer Investigators is provided in the Supplementary Appendix, available at NEJM.org.

 

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