Switching to DOACs associated with higher bleeding risk in frail elderly Asian patients with AF
In a Korean retrospective observational study among frail elderly Asian AF patients who were stably maintained on warfarin, switching warfarin to DOACs was associated with higher risks of bleeding, thromboembolic events, net clinical outcome, and all-cause mortality compared with warfarin treatment.
This summary is based on the publication of Lee SR, Go YH, Choi EK, et al. - Switching from warfarin to direct oral anticoagulants in frail elderly Asian patients with atrial fibrillation: a Korean nationwide study. Eur Heart J. 2026 Feb 27:ehaf999. [Online ahead of print]. doi: 10.1093/eurheartj/ehaf999.
Introduction and methods
Background
In the Dutch FRAIL-AF trial among frail elderly patients who were stably managed on warfarin, switching from warfarin to DOACs increased bleeding risk, while thromboembolic risk remained comparable [1]. It remains unclear whether warfarin is inferior to DOACs in Asian patients who were well-managed on long-term warfarin.
Aim of the study
The aim of the study was to evaluate the safety and effectiveness of switching from warfarin to DOACs in frail elderly Asian patients with AF.
Methods
This nationwide Korean, retrospective, observational cohort study included 12,461 frail elderly (≥75 years) patients with non-valvular AF who were receiving warfarin for stroke prevention between January 2013 and August 2015 from the Korean National Health Insurance Service (NHIS) database. Key inclusion criteria were a Hospital Frailty Risk Score ≥5 and no major bleeding or thromboembolic events during warfarin use from January 2013 to August 2015.
Patients were categorized into two groups: those who remained on warfarin (n=9,112), and those who switched to a DOAC at least once (n=3,349). Patients were followed for up to 1 year.
Outcomes
The primary outcome was major bleeding. Secondary outcomes included thromboembolic events, net clinical outcome, defined as a composite of major bleeding and thromboembolic events, and all-cause mortality.
Main results
- During 11,842 person-years of follow-up, switching from warfarin to a DOAC was associated with significantly worse clinical outcomes compared with remaining on warfarin:
- Major bleeding: adjusted HR 1.36 (95%CI: 1.01–1.81; P=0.040)
- Thromboembolic events: adjusted HR 1.61 (95%CI: 1.30–2.00; P<0.001)
- Net clinical outcome: adjusted HR 1.58 (95%CI: 1.29–1.94; P<0.001)
- All-cause mortality: adjusted HR 1.20 (95%CI: 1.02–1.42; P=0.029)
- Subgroup analyses showed consistent trends toward higher risks of clinical outcomes with switching to DOACs compared with warfarin treatment across age, sex, renal function, and frailty (all P for interaction>0.05).
Conclusion
Among frail elderly Asian patients with AF who were stable on warfarin, switching to a DOAC was associated with higher risks of major bleeding, thromboembolic events, net clinical outcome, and all-cause mortality compared with warfarin treatment. According to the authors “switching to DOACs in this population should be approached cautiously, with a strong emphasis on individualized anticoagulation strategies.”
References
- Joosten LPT, van Doorn S, van de Ven PM, Köhlen BTG, Nierman MC, Koek HL, et al. Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anti coagulant in frail older patients with atrial fibrillation: results of the FRAIL-AF rando mized controlled trial. Circulation 2024;149:279–89. https://doi.org/10.1161/ circulationaha.123.066485