Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin

IF 22.3 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Journal of the American College of Cardiology Pub Date : 2025-08-04 DOI:10.1016/j.jacc.2025.05.060

Andre M. Nicolau MD , Robert P. Giugliano MD, SM , Andre Zimerman MD, PhD , Jonathan Afilalo MD, MSc , Baris Gencer MD, MPH , Jan Steffel MD , Michael G. Palazzolo MS , John W. Eikelboom MBBS , Christopher B. Granger MD , Manesh R. Patel MD , Renato D. Lopes MD, PhD , Bernard J. Gersh MD , Belal Suleiman MD , Joris R. de Groot MD , Mauricio I. Scanavacca MD , Christian T. Ruff MD, MPH , Elliott M. Antman MD , Eugene Braunwald MD , Lars Wallentin MD

{"title":"Outcomes in Older Patients After Switching to a Newer Anticoagulant or Remaining on Warfarin","authors":"Andre M. Nicolau MD , Robert P. Giugliano MD, SM , Andre Zimerman MD, PhD , Jonathan Afilalo MD, MSc , Baris Gencer MD, MPH , Jan Steffel MD , Michael G. Palazzolo MS , John W. Eikelboom MBBS , Christopher B. Granger MD , Manesh R. Patel MD , Renato D. Lopes MD, PhD , Bernard J. Gersh MD , Belal Suleiman MD , Joris R. de Groot MD , Mauricio I. Scanavacca MD , Christian T. Ruff MD, MPH , Elliott M. Antman MD , Eugene Braunwald MD , Lars Wallentin MD","doi":"10.1016/j.jacc.2025.05.060","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Whether frail, elderly patients with atrial fibrillation (AF) on a vitamin K antagonist (VKA) should switch to a direct-acting oral anticoagulant (DOAC) was studied in the FRAIL-AF trial and remains controversial.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to evaluate, in the COMBINE-AF data set, the impact on clinical outcomes of switching frail, elderly AF patients from VKA to DOAC.</div></div><div><h3>Methods</h3><div>COMBINE-AF consists of individual patient-level data from 71,683 patients with AF in 4 randomized clinical trials comparing DOAC vs warfarin. Frailty was evaluated using a frailty index derived from a modified Rockwood’s Accumulation Model including 18 age-related conditions. Patients with a frailty index score above the median were considered frail. Prespecified outcomes were stroke or systemic embolic events, bleeding events, death, and a net clinical outcome combining these events.</div></div><div><h3>Results</h3><div>We identified 5,913 patients who were frail, elderly (age ≥75 years), and VKA-experienced and 52,721 patients who did not meet all 3 of these criteria. Patients were randomized to a standard-dose (SD) DOAC or warfarin. After 27 months median follow-up, there was no heterogeneity in treatment effect with SD-DOAC vs warfarin among those who met all 3 criteria vs those who did not for the endpoints of stroke or systemic embolic events (HR: 0.83 vs 0.81; <em>P</em><sub><em>int</em></sub> = 0.75) or for death (HR: 0.95 vs 0.91; <em>P</em><sub><em>int</em></sub> = 0.54). Major bleeding was similar with SD-DOAC vs warfarin in frail, elderly, VKA-experienced patients (HR: 1.06 [95% CI: 0.90-1.25]), while it was significantly reduced with SD-DOAC in patients without all 3 criteria (HR: 0.82 [95% CI: 0.76-0.89]; <em>P</em><sub><em>int</em></sub> = 0.007). Likewise, the net clinical outcome was similar in the frail, elderly, VKA-experienced patients with SD-DOAC vs warfarin (HR: 1.01 [95% CI: 0.91-1.13]), while significantly reduced with SD-DOAC patients without all 3 criteria (HR: 0.89 [95% CI: 0.85-0.93]; <em>P</em><sub><em>int</em></sub> = 0.028). Fatal and intracranial bleeding were significantly reduced with SD-DOAC in both subgroups to a similar degree (both <em>P</em><sub><em>int</em></sub> > 0.05), while gastrointestinal bleeding with SD-DOAC was increased to a greater degree in frail, elderly, VKA-experienced patients (HR: 1.83 [95% CI: 1.42-2.36]) compared with those without all 3 criteria (HR: 1.23 [95% CI: 1.09-1.39]; <em>P</em><sub><em>int</em></sub> = 0.006).</div></div><div><h3>Conclusions</h3><div>Frail, elderly, VKA-experienced patients with AF switched to SD-DOAC experienced significant reductions in stroke or systemic embolism, fatal and intracranial bleeding, and death. Gastrointestinal bleeding was increased with SD-DOAC, while major bleeding and the primary net clinical outcome were similar. Based on these findings, SD-DOAC is a reasonable choice for frail, elderly, VKA-experienced patients to reduce stroke and systemic embolism, death, and the most serious types of bleeding.</div></div>","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"86 6","pages":"Pages 426-439"},"PeriodicalIF":22.3000,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American College of Cardiology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0735109725067178","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Whether frail, elderly patients with atrial fibrillation (AF) on a vitamin K antagonist (VKA) should switch to a direct-acting oral anticoagulant (DOAC) was studied in the FRAIL-AF trial and remains controversial.

Objectives

The purpose of this study was to evaluate, in the COMBINE-AF data set, the impact on clinical outcomes of switching frail, elderly AF patients from VKA to DOAC.

Methods

COMBINE-AF consists of individual patient-level data from 71,683 patients with AF in 4 randomized clinical trials comparing DOAC vs warfarin. Frailty was evaluated using a frailty index derived from a modified Rockwood’s Accumulation Model including 18 age-related conditions. Patients with a frailty index score above the median were considered frail. Prespecified outcomes were stroke or systemic embolic events, bleeding events, death, and a net clinical outcome combining these events.

Results

We identified 5,913 patients who were frail, elderly (age ≥75 years), and VKA-experienced and 52,721 patients who did not meet all 3 of these criteria. Patients were randomized to a standard-dose (SD) DOAC or warfarin. After 27 months median follow-up, there was no heterogeneity in treatment effect with SD-DOAC vs warfarin among those who met all 3 criteria vs those who did not for the endpoints of stroke or systemic embolic events (HR: 0.83 vs 0.81; P_int = 0.75) or for death (HR: 0.95 vs 0.91; P_int = 0.54). Major bleeding was similar with SD-DOAC vs warfarin in frail, elderly, VKA-experienced patients (HR: 1.06 [95% CI: 0.90-1.25]), while it was significantly reduced with SD-DOAC in patients without all 3 criteria (HR: 0.82 [95% CI: 0.76-0.89]; P_int = 0.007). Likewise, the net clinical outcome was similar in the frail, elderly, VKA-experienced patients with SD-DOAC vs warfarin (HR: 1.01 [95% CI: 0.91-1.13]), while significantly reduced with SD-DOAC patients without all 3 criteria (HR: 0.89 [95% CI: 0.85-0.93]; P_int = 0.028). Fatal and intracranial bleeding were significantly reduced with SD-DOAC in both subgroups to a similar degree (both P_int > 0.05), while gastrointestinal bleeding with SD-DOAC was increased to a greater degree in frail, elderly, VKA-experienced patients (HR: 1.83 [95% CI: 1.42-2.36]) compared with those without all 3 criteria (HR: 1.23 [95% CI: 1.09-1.39]; P_int = 0.006).

Conclusions

Frail, elderly, VKA-experienced patients with AF switched to SD-DOAC experienced significant reductions in stroke or systemic embolism, fatal and intracranial bleeding, and death. Gastrointestinal bleeding was increased with SD-DOAC, while major bleeding and the primary net clinical outcome were similar. Based on these findings, SD-DOAC is a reasonable choice for frail, elderly, VKA-experienced patients to reduce stroke and systemic embolism, death, and the most serious types of bleeding.

Abstract Image

查看原文本刊更多论文

老年患者改用新型抗凝剂或继续使用华法林后的预后

背景：虚弱的老年心房颤动（AF）患者服用维生素K拮抗剂（VKA）是否应该切换到直接作用的口服抗凝剂（DOAC），在虚弱的心房颤动（AF）试验中进行了研究，但仍存在争议。目的：本研究的目的是在合并房颤的数据集中，评估虚弱的老年房颤患者从VKA转为DOAC对临床结果的影响。方法：combine -AF包括4项比较DOAC与华法林的随机临床试验中71683例房颤患者的个体患者水平数据。脆弱性评估使用脆弱性指数衍生自改良的Rockwood积累模型，包括18个与年龄相关的条件。虚弱指数评分高于中位数的患者被认为是虚弱的。预先指定的结局是中风或全身性栓塞事件、出血事件、死亡，以及结合这些事件的净临床结局。结果我们确定了5,913例体弱、老年（年龄≥75岁）和有vka经历的患者，以及52,721例不符合所有这3个标准的患者。患者被随机分配到标准剂量DOAC或华法林。中位随访27个月后，在卒中或系统性栓塞事件终点方面，符合所有3个标准的患者与不符合3个标准的患者相比，SD-DOAC与华法林的治疗效果没有异质性(HR: 0.83 vs 0.81；品脱= 0.75)或死亡(风险比：0.95 vs 0.91；品脱= 0.54)。SD-DOAC与华法林在体弱、老年、有vka经历的患者中大出血相似（HR: 1.06 [95% CI: 0.90-1.25]），而在没有所有3项标准的患者中，SD-DOAC显著减少大出血(HR: 0.82 [95% CI: 0.76-0.89]；品脱= 0.007)。同样，SD-DOAC与华法林治疗的体弱、老年、有vka经历的患者的净临床结果相似（HR: 1.01 [95% CI: 0.91-1.13]），而没有所有3个标准的SD-DOAC患者的净临床结果显著降低(HR: 0.89 [95% CI: 0.85-0.93]；品脱= 0.028)。SD-DOAC在两个亚组中均显著减少致死性出血和颅内出血，且减少程度相似(均为Pint >；0.05)，而与没有所有3项标准的患者（HR: 1.23 [95% CI: 1.09-1.39]）相比，虚弱、老年、有vka经历的患者（HR: 1.83 [95% CI: 1.42-2.36]） SD-DOAC的胃肠道出血增加程度更高；品脱= 0.006)。结论：体弱多病、老年、有vka经验的房颤患者改用SD-DOAC后，卒中或全身性栓塞、致命性和颅内出血以及死亡的发生率显著降低。SD-DOAC增加了胃肠道出血，而大出血和主要净临床结果相似。基于这些发现，SD-DOAC是体弱、老年、有vka经验的患者减少中风、全身性栓塞、死亡和最严重类型出血的合理选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of the American College of Cardiology 医学-心血管系统

CiteScore

42.70

自引率

3.30%

发文量

5097

审稿时长

2-4 weeks

期刊介绍： The Journal of the American College of Cardiology (JACC) publishes peer-reviewed articles highlighting all aspects of cardiovascular disease, including original clinical studies, experimental investigations with clear clinical relevance, state-of-the-art papers and viewpoints. Content Profile: -Original Investigations -JACC State-of-the-Art Reviews -JACC Review Topics of the Week -Guidelines & Clinical Documents -JACC Guideline Comparisons -JACC Scientific Expert Panels -Cardiovascular Medicine & Society -Editorial Comments (accompanying every Original Investigation) -Research Letters -Fellows-in-Training/Early Career Professional Pages -Editor’s Pages from the Editor-in-Chief or other invited thought leaders