Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (B.A.B., J.-G.P., G.E.M.M., E.M.A., C.T.R., E.B., R.P.G.).
Wills Eye Institute, Philadelphia, PA (R.A.H.).
Circ Cardiovasc Qual Outcomes. 2024 Jul;17(7):e010561. doi: 10.1161/CIRCOUTCOMES.123.010561. Epub 2024 Jun 3.
Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events.
ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin. In an exploratory analysis, we analyzed the trial outcomes using an unmatched win ratio approach. The win ratio for each edoxaban regimen was the total number of edoxaban wins divided by the number of warfarin wins for the following ranked clinical outcomes: 1: death; 2: hemorrhagic stroke; 3: ischemic stroke/systemic embolic event/epidural or subdural bleeding; 4: noncerebral International Society on Thrombosis and Haemostasis major bleeding; and 5: cardiovascular hospitalization.
21 105 patients were randomized to higher dose edoxaban regimen (N=7035), lower dose edoxaban regimen (N=7034), or warfarin (N=7046), yielding >49 million pairs for each treatment comparison. The median age was 72 years, 38% were women, and 59% had prior vitamin K antagonist use. The win ratio was 1.11 (95% CI, 1.05-1.18) for higher dose edoxaban regimen versus warfarin and 1.11 (95% CI, 1.05-1.18) for lower dose edoxaban regimen versus warfarin. The favorable impacts of edoxaban on death (34% of wins) and cardiovascular hospitalization (41% of wins) were the major contributors to the win ratio. Results consistently favored edoxaban in subgroups based on creatine clearance and dose reduction at baseline, with heightened benefit among those without prior vitamin K antagonist use.
In a win ratio analysis of the ENGAGE AF-TIMI 48 trial, both dose regimens of edoxaban were superior to warfarin for the net clinical outcome incorporating ischemic and bleeding events. As the win ratio emphasizes the most severe clinical events, this analysis supports the superiority of edoxaban over warfarin in patients with atrial fibrillation.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.
心血管试验通常使用复合终点和首次事件时间模型。我们旨在使用赢率比较依度沙班与华法林，赢率提供了与首次事件分析互补的数据，强调最严重的临床事件。
ENGAGE AF-TIMI 48（房颤-血栓溶栓心肌梗死 48 时新型 Xa 因子抗凝剂）是一项双盲、随机试验，将房颤患者以 1:1:1 的比例随机分配至高剂量依度沙班组（每日 60/30mg）、低剂量依度沙班组（每日 30/15mg）或华法林组。在一项探索性分析中，我们使用非匹配赢率方法分析了试验结果。每个依度沙班组的赢率为依度沙班的总赢数除以华法林的赢数，用于排名以下临床结局：1：死亡；2：出血性卒中；3：缺血性卒中/全身性栓塞事件/硬膜外或蛛网膜下腔出血；4：非脑国际血栓与止血协会大出血；5：心血管住院。
21105 名患者被随机分配至高剂量依度沙班组（N=7035）、低剂量依度沙班组（N=7034）或华法林组（N=7046），每种治疗比较的配对数均超过 4900 万对。中位年龄为 72 岁，38%为女性，59%有既往维生素 K 拮抗剂使用史。高剂量依度沙班组与华法林相比的赢率为 1.11（95%CI，1.05-1.18），低剂量依度沙班组与华法林相比的赢率为 1.11（95%CI，1.05-1.18）。依度沙班对死亡（34%的赢）和心血管住院（41%的赢）的有利影响是赢率的主要贡献因素。基于肌酐清除率和基线时剂量减少的亚组分析结果一致表明依度沙班更优，无既往维生素 K 拮抗剂使用史的患者获益更高。
在 ENGAGE AF-TIMI 48 试验的赢率分析中，两种剂量的依度沙班在纳入缺血性和出血性事件的净临床结局方面均优于华法林。由于赢率强调最严重的临床事件，本分析支持在房颤患者中依度沙班优于华法林。
