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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?

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?

Population

369,480 AF patients initiating apixaban or rivaroxaban in Veterans Affairs EHR

Comparison

Reduced-dose vs standard-dose DOACs

Design

Observational analysis

Key result

Reduced-dose DOACs were associated with a higher risk of stroke or systemic embolism (HR 1.06; 95% CI 1.03-1.09; P<0.001) but a lower risk of major bleeding compared to standard-dose DOACs.

Authors

YLYUN LEEYLYILU LINLDLIPING DU

Discussion

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Overview

Should not yet change dosing practice in AF; leaves open optimal strategies pending randomized confirmation.

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).

Study Design

Type

Observational (n=369,480)

Multicenter

Yes

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 predominantly male patients with atrial fibrillation initiating apixaban or rivaroxaban, analyzed using Veterans Affairs EHR data from 2011 to 2025.
E
Exposure
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

Main Result

Hazard Ratio: 1.06 (95% CI 1.03–1.09)

p-value: p=<0.001

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) 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 (HR 1.06; 95% CI 1.03-1.09; P<0.001) but a lower risk of major bleeding compared to standard-dose DOACs.

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