From the Baim Institute for Clinical Research (C.P.C., J.L.J.), Brigham and Women's Hospital, Heart and Vascular Center, and Harvard Medical School (C.P.C., D.L.B.), and the Cardiology Division, Massachusetts General Hospital, and Harvard Medical School (J.L.J.) - all in Boston; Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden (J.O.); the Institute of Cardiovascular Sciences, University of Birmingham, Birmingham (G.Y.H.L.), Boehringer Ingelheim, Bracknell (R.H., J.M.), and Imperial College, London, London (P.G.S.) - all in the United Kingdom; Cleveland Clinic, Cleveland (S.G.E.); Kyoto University, Department of Cardiovascular Medicine, Kyoto, Japan (T.K.); Aarhus University Hospital, Skejby, Denmark (M.M.); University Heart and Vascular Center, Budapest, Hungary (B.M.); Klinikum der Stadt Ludwigshafen am Rhein, Medizinische Klinik B, Ludwigshafen (U.Z.), Boehringer Ingelheim, Ingelheim (S.G., M.N., E.K.), and Johann Wolfgang Goethe University, Department of Medicine, Division of Cardiology, Frankfurt am Main (S.H.H.) - all in Germany; St. Antonius Ziekenhuis, Nieuwegein, the Netherlands (J.M.B.); and the French Alliance for Cardiovascular Trials, F-CRIN Network, DHU FIRE, Université Paris Diderot, INSERM Unité 1148, and Hôpital Bichat Assistance Publique, Paris (P.G.S.).
N Engl J Med. 2017 Oct 19;377(16):1513-1524. doi: 10.1056/NEJMoa1708454. Epub 2017 Aug 27.
Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.
In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (≥80 years of age; ≥70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization.
The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.
Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y inhibitor than among those who received triple therapy with warfarin, a P2Y inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events. (Funded by Boehringer Ingelheim; RE-DUAL PCI ClinicalTrials.gov number, NCT02164864 .).
在接受经皮冠状动脉介入治疗（PCI）的房颤患者中，华法林联合两种抗血小板药物的三联抗栓治疗是标准治疗方案，但这种治疗方案与出血风险高相关。
在这项多中心试验中，我们将 2725 名接受过 PCI 的房颤患者随机分为三联治疗组（华法林联合 P2Y 抑制剂[氯吡格雷或替格瑞洛]和阿司匹林[1-3 个月]）或双联治疗组（达比加群 110mg 或 150mg，每日两次，联合 P2Y 抑制剂[氯吡格雷或替格瑞洛]且不使用阿司匹林）。在美国以外地区，老年患者（≥80 岁；日本≥70 岁）被随机分配至 110mg 双联治疗组或三联治疗组。主要终点是随访期间主要或临床相关非大出血事件（平均随访 14 个月）。该试验还检测了达比加群（两种剂量联合）双联治疗与华法林三联治疗在血栓栓塞事件（心肌梗死、卒中和全身性栓塞）复合终点、死亡或未计划血运重建方面的非劣效性。
110mg 双联治疗组的主要终点发生率为 15.4%，三联治疗组为 26.9%（风险比，0.52；95%置信区间[CI]，0.42 至 0.63；非劣效性 P<0.001；优效性 P<0.001）；150mg 双联治疗组的发生率为 20.2%，相应的三联治疗组为 25.7%，该组不包括美国以外地区的老年患者（风险比，0.72；95%CI，0.58 至 0.88；非劣效性 P<0.001）。双联治疗组的复合疗效终点发生率为 13.7%，三联治疗组为 13.4%（风险比，1.04；95%CI，0.84 至 1.29；非劣效性 P=0.005）。各组严重不良事件发生率无显著差异。
在接受 PCI 的房颤患者中，与华法林三联治疗相比，达比加群和 P2Y 抑制剂双联治疗的出血风险更低。双联治疗在血栓栓塞事件风险方面不劣于三联治疗。（由勃林格殷格翰公司资助；RE-DUAL PCI 临床试验.gov 编号，NCT02164864）。
