Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
BMC Med. 2020 Dec 24;18(1):401. doi: 10.1186/s12916-020-01870-w.
Atrial fibrillation (AF) is common in older people with frailty and is associated with an increased risk of stroke and systemic embolism. Whilst oral anticoagulation is associated with a reduction in this risk, there is a lack of data on the safety and efficacy of direct oral anticoagulants (DOACs) in people with frailty. This study aims to report clinical outcomes of patients with AF in the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial by frailty status.
Post hoc analysis of 20,867 participants in the ENGAGE AF-TIMI 48 trial, representing 98.8% of those randomised. This double-blinded double-dummy trial compared two once-daily regimens of edoxaban (a DOAC) with warfarin. Participants were categorised as fit, living with pre-frailty, mild-moderate, or severe frailty according to a standardised index, based upon the cumulative deficit model. The primary efficacy endpoint was stroke or systemic embolism and the safety endpoint was major bleeding.
A fifth (19.6%) of the study population had frailty (fit: n = 4459, pre-frailty: n = 12,326, mild-moderate frailty: n = 3722, severe frailty: n = 360). On average over the follow-up period, the risk of stroke or systemic embolism increased by 37% (adjusted HR 1.37, 95% CI 1.19-1.58) and major bleeding by 42% (adjusted HR 1.42, 1.27-1.59) for each 0.1 increase in the frailty index (four additional health deficits). Edoxaban was associated with similar efficacy to warfarin in every frailty category, and a lower risk of bleeding than warfarin in all but those living with severe frailty.
Edoxaban was similarly efficacious to warfarin across the frailty spectrum and was associated with lower rates of bleeding except in those with severe frailty. Overall, with increasing frailty, there was an increase in stroke and bleeding risk. There is a need for high-quality, frailty-specific population randomised control trials to guide therapy in this vulnerable population.
ClinicalTrials.gov NCT00781391 . First registered on 28 October 2008.
心房颤动（AF）在虚弱的老年人中很常见，与中风和全身性栓塞的风险增加有关。虽然口服抗凝剂可降低这种风险，但关于虚弱患者使用直接口服抗凝剂（DOAC）的安全性和有效性的数据有限。本研究旨在报告心房颤动-血栓溶解治疗 48 试验中有效抗凝因子 Xa 新一代在心房颤动中的临床结果（ENGAGE AF-TIMI 48）按虚弱状态分类的患者。
对 ENGAGE AF-TIMI 48 试验的 20867 名参与者进行事后分析，占随机分配人数的 98.8%。这项双盲双模拟试验比较了两种每日一次的依度沙班（一种 DOAC）与华法林的疗效。根据累积缺陷模型，根据标准化指数，参与者被归类为健康、患有预虚弱、轻度-中度或严重虚弱。主要疗效终点为中风或全身性栓塞，安全性终点为大出血。
研究人群中有五分之一（19.6%）患有虚弱（健康：n=4459，预虚弱：n=12326，轻度-中度虚弱：n=3722，严重虚弱：n=360）。在平均随访期间，每增加 0.1 分的虚弱指数（增加 4 项健康缺陷），中风或全身性栓塞的风险增加 37%（调整后的 HR 1.37，95%CI 1.19-1.58），大出血的风险增加 42%（调整后的 HR 1.42，1.27-1.59）。依度沙班在每个虚弱类别中的疗效与华法林相似，除了严重虚弱的患者外，出血风险也低于华法林。
依度沙班在虚弱谱中与华法林同样有效，出血率低于华法林，除了严重虚弱的患者。总的来说，随着虚弱程度的增加，中风和出血的风险也会增加。需要高质量的、针对虚弱人群的随机对照试验来指导这一脆弱人群的治疗。
ClinicalTrials.gov NCT00781391。于 2008 年 10 月 28 日首次注册。
