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June 7, 2026Diabetes

2188-P: Clinical Benefits and Risks of Reduced-Dose vs. Standard-Dose Direct Oral Anticoagulants in Patients with Atrial Fibrillation: An Observational Analysis of Veterans Affairs Data

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Why the study?

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?

Population

369,480 patients with atrial fibrillation initiating apixaban or rivaroxaban, excluding those with…

Comparison

Reduced-dose direct oral anticoagulants vs Standard-dose direct oral anticoagulants

Design

Cohort

Authors

YLYUN LEEYLYILU LINLDLIPING DU

Discussion

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Overview

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.

Key Points

  • This study aimed to compare outcomes of reduced vs. standard-dose direct oral anticoagulants in patients with atrial fibrillation.
  • Analyzed Veterans Affairs EHR data from Jan 2011 to Oct 2025
  • Identified 369,480 patients initiating apixaban or rivaroxaban
  • Used Cox proportional hazards models to estimate stroke and bleeding risks.
  • Reduced-dose DOACs associated with higher stroke/systemic embolism risk (HR = 1.06; p < 0.001)
  • Lower major bleeding risk observed with reduced-dose DOACs (HR = 0.92; p < 0.001)
  • In patients < 65, reduced-dose linked to higher stroke (HR = 1.31; p = 0.001) and major bleeding risk (HR = 1.13; p = 0.04).

Structured PICO

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?

P
Population
369,480 patients with atrial fibrillation 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. Predominantly male (98%), with a mean age of 74.17 years in the standard-dose group and 84.13 years in the reduced-dose group.
I
Intervention
Reduced-dose direct oral anticoagulants (apixaban 2.5 mg or rivaroxaban 15 mg)
C
Comparator
Standard-dose direct oral anticoagulants (apixaban 5 mg or rivaroxaban 20 mg)
O
Outcome
Stroke prevention (any stroke/systemic embolism [SE] and ischemic stroke) and bleeding risks (any major bleeding [MB], intracranial, gastrointestinal, and genitourinary bleedings)hard clinical

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.

Cite This Study

LEE et al. (2026) studied this question.

synapsesocial.com/papers/6a250c687def13d035e1c8ebhttps://doi.org/10.2337/db26-2188-p
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Efficacy and safety of low-dose vs. standard-dose direct oral anticoagulants for secondary prevention of venous thromboembolism: A systematic review and meta-analysis2025
  2. 2Full-dose versus reduced-dose comparison of direct oral anticoagulants for extended treatment of venous thromboembolism: a systematic review and meta-analysis of randomized controlled trials2025 · 1 citations
  3. 3Efficacy and safety of reduced-dose versus full-dose direct oral anticoagulants for extended treatment of venous thromboembolism: A meta-analysis with trial sequential analysis and reconstructed time-to-event data2025 · 5 citations
  4. 4From prescription to outcome: real-world utilization of direct oral anticoagulants in atrial fibrillation across Europe2026
  5. 5Anticoagulation for Atrial Fibrillation with Intermediate Stroke Risk2026