Key result
Reduced-dose DOACs linked to ~6% higher stroke risk but less major bleeding vs standard doses.
Why the study?
Reduced-dose DOACs are commonly used in clinical practice for atrial fibrillation despite limited comparative evidence on their outcomes compared with standard doses.
Does reduced-dose DOAC therapy compared to standard-dose DOAC therapy alter the risk of stroke/systemic embolism and major bleeding in patients with atrial fibrillation?
Observational (n=369,480)
Yes
Does reduced-dose DOAC therapy compared to standard-dose DOAC therapy alter the risk of stroke/systemic embolism and major bleeding in patients with atrial fibrillation?
Answers are grounded in this paper and cite their sources.
In a large observational cohort of Veterans Affairs patients with atrial fibrillation, reduced-dose DOACs were associated with a higher risk of stroke/systemic embolism but a lower risk of major bleeding compared to standard-dose DOACs, with important variations by age and race.
Introduction and Objective: RCTs show direct oral anticoagulants (DOACs) are effective for non-valvular atrial fibrillation (AF) with lower major bleeding risk. While reduced doses are intended for select high-risk populations, they are commonly used in clinical practice despite limited comparative evidence. This study aimed to compare the outcomes associated with reduced-dose versus standard-dose DOACs in patients with AF. Methods: Using Veterans Affairs EHR (Jan 2011-Oct 2025), we identified 369,480 AF patients initiating apixaban (2.5/5 mg) or rivaroxaban (15/20 mg), excluding those with malignancy, renal impairment, liver failure, venous thromboembolism, and moderate-to-severe mitral stenosis. Patients were categorized by dose as standard (N = 332,630) or reduced (N = 36,850). Cox proportional hazards models estimated stroke prevention (any stroke/systemic embolism [SE] and ischemic stroke) and bleeding risks (any major bleeding [MB], intracranial, gastrointestinal, and genitourinary bleedings). Analyses were further stratified by age (< 65, 65-74, and ≥ 75 years) and race. Results: The study population was predominantly male (98%), with a mean age of 74.17 years (SD = 9.06) in the standard-dose group and 84.13 years (SD = 7.73) in the reduced-dose group. Overall, reduced-dosing was associated with higher risk of any stroke/SE (HR = 1.06; 95% CI: 1.03-1.09; p < 0.001) but lower MB risk (HR = 0.92; 95% CI: 0.90-0.94; p < 0.001). In subgroup analyses, among patients ≥ 75, reduced-dosing was associated with lower MB risk (HR = 0.87; p < 0.001). However, in patients < 65, it was associated with higher risks of both stroke/SE (HR = 1.31; p = 0.001) and MB (HR = 1.13; p = 0.04). Although the increased stroke risk was consistent for White and Black populations, Asian patients receiving reduced-dose DOACs showed a higher relative risk of MB (HR = 1.24; p = 0.03). Conclusion: Appropriate dose selection for DOACs is critical to balance stroke prevention and bleeding risk in treating AF patients. Disclosure Y. Lee: None. Y. Lin: None. L. Du: None. V. Fonseca: Consultant; Current; Abbott Diabetes. Stock/Shareholder; Current; BRAVO4HEALTH, LLC. Consultant; Ended; Bayer AG. Consultant; Current; Eli Lilly and Company, Corcept Therapeutics, Regeneron Pharmaceuticals Inc., Boehringer Ingelheim International GmbH. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. L. Shi: None.
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LEE et al. (2026) conducted an observational in Atrial Fibrillation (n=369,480). Reduced-dose direct oral anticoagulants vs. Standard-dose direct oral anticoagulants was evaluated on any stroke/systemic embolism [SE] (HR 1.06, 95% CI 1.03-1.09, p=<0.001). Reduced-dose DOACs were associated with a higher risk of stroke or systemic embolism but a lower risk of major bleeding compared to standard-dose DOACs.
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