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.).
N Engl J Med. 2017 Mar 30;376(13):1211-1222. doi: 10.1056/NEJMoa1700518. Epub 2017 Mar 18.
Although many patients with venous thromboembolism require extended treatment, it is uncertain whether it is better to use full- or lower-intensity anticoagulation therapy or aspirin.
In this randomized, double-blind, phase 3 study, we assigned 3396 patients with venous thromboembolism to receive either once-daily rivaroxaban (at doses of 20 mg or 10 mg) or 100 mg of aspirin. All the study patients had completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation. Study drugs were administered for up to 12 months. The primary efficacy outcome was symptomatic recurrent fatal or nonfatal venous thromboembolism, and the principal safety outcome was major bleeding.
A total of 3365 patients were included in the intention-to-treat analyses (median treatment duration, 351 days). The primary efficacy outcome occurred in 17 of 1107 patients (1.5%) receiving 20 mg of rivaroxaban and in 13 of 1127 patients (1.2%) receiving 10 mg of rivaroxaban, as compared with 50 of 1131 patients (4.4%) receiving aspirin (hazard ratio for 20 mg of rivaroxaban vs. aspirin, 0.34; 95% confidence interval [CI], 0.20 to 0.59; hazard ratio for 10 mg of rivaroxaban vs. aspirin, 0.26; 95% CI, 0.14 to 0.47; P<0.001 for both comparisons). Rates of major bleeding were 0.5% in the group receiving 20 mg of rivaroxaban, 0.4% in the group receiving 10 mg of rivaroxaban, and 0.3% in the aspirin group; the rates of clinically relevant nonmajor bleeding were 2.7%, 2.0%, and 1.8%, respectively. The incidence of adverse events was similar in all three groups.
Among patients with venous thromboembolism in equipoise for continued anticoagulation, the risk of a recurrent event was significantly lower with rivaroxaban at either a treatment dose (20 mg) or a prophylactic dose (10 mg) than with aspirin, without a significant increase in bleeding rates. (Funded by Bayer Pharmaceuticals; EINSTEIN CHOICE ClinicalTrials.gov number, NCT02064439 .).
虽然许多患有静脉血栓栓塞症的患者需要延长治疗，但尚不确定使用全强度或低强度抗凝治疗或阿司匹林更好。
在这项随机、双盲、3 期研究中，我们将 3396 例静脉血栓栓塞患者分配接受每日一次利伐沙班（剂量为 20 毫克或 10 毫克）或 100 毫克阿司匹林治疗。所有研究患者均已完成 6 至 12 个月的抗凝治疗，并且在需要继续抗凝治疗方面处于平衡状态。研究药物的使用时间最长为 12 个月。主要疗效结局是有症状的复发性致命或非致命静脉血栓栓塞，主要安全性结局是大出血。
共有 3365 例患者纳入意向治疗分析（中位治疗时间为 351 天）。17 例（1.5%）接受 20 毫克利伐沙班的患者和 13 例（1.2%）接受 10 毫克利伐沙班的患者出现主要疗效结局，而 1131 例（4.4%）接受阿司匹林的患者中 50 例出现该结局（20 毫克利伐沙班与阿司匹林相比的风险比，0.34；95%置信区间 [CI]，0.20 至 0.59；10 毫克利伐沙班与阿司匹林相比的风险比，0.26；95%CI，0.14 至 0.47；两者均<0.001）。接受 20 毫克利伐沙班的患者大出血发生率为 0.5%，接受 10 毫克利伐沙班的患者为 0.4%，接受阿司匹林的患者为 0.3%；临床相关非大出血发生率分别为 2.7%、2.0%和 1.8%。三组患者的不良反应发生率相似。
在需要继续抗凝治疗且处于平衡状态的静脉血栓栓塞患者中，与阿司匹林相比，利伐沙班（治疗剂量 20 毫克或预防剂量 10 毫克）的复发事件风险显著降低，且出血率无显著增加。（拜耳制药公司资助；EINSTEIN CHOICE 临床试验.gov 编号，NCT02064439）。
