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May 31, 2026Journal of StrokeOpen Access

Divergent Small Vessel Disease Burden in Warfarin-Associated and Direct Oral Anticoagulant-Associated Intracerebral Hemorrhage

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Why the study?

Whether cerebral small vessel disease burden differs between warfarin-associated and DOAC-associated intracerebral hemorrhage remains unclear.

Does cerebral small vessel disease burden differ between DOAC-associated, warfarin-associated, and non-anticoagulant-associated spontaneous intracerebral hemorrhage?

Population

Consecutive patients aged ≥20 years admitted for spontaneous ICH

Comparison

DOAC users vs warfarin users vs matched AC non-users

Design

Prospective cohort study

Key result

Warfarin users who experienced intracerebral hemorrhage demonstrated a significantly lower small vessel disease burden compared with DOAC users (cOR 0.22) and anticoagulant non-users.

Authors

STSung-Chun TangYCYa‐Fang ChenCCChih-Hao Chen

Discussion

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Overview

Does not alter anticoagulation decisions in ICH; leaves open whether SVD burden differs by prior anticoagulant type.

Key Points

  • This study aims to compare the burden of cerebral small vessel disease (SVD) between warfarin-associated and direct oral anticoagulant (DOAC)-associated intracerebral hemorrhage (ICH).
  • Prospective cohort study of patients aged ≥20 years with spontaneous ICH admitted to the National Taiwan University Hospital.
  • Cohorts included DOAC users and warfarin users matched with AC non-users by sex and age.
  • Brain CT assessed SVD burden using a validated scoring system based on white matter lesions, lacunes, and cerebral atrophy.
  • DOAC users showed a higher SVD burden compared to warfarin users as per CT scoring.
  • Significantly higher hematoma volume was observed in the DOAC group during initial assessments.
  • Hematoma expansion rates were analyzed, providing insights into the severity of ICH between groups.

Study Design

Type

Cohort (n=384)

Multicenter

No

Structured PICO

Does cerebral small vessel disease burden differ between DOAC-associated, warfarin-associated, and non-anticoagulant-associated spontaneous intracerebral hemorrhage?

P
Population
Consecutive patients aged ≥20 years admitted for spontaneous intracerebral hemorrhage. Excluded: pure intraventricular hemorrhage, tumor bleeding, or cerebral venous sinus thrombosis.
I
Intervention
Direct oral anticoagulants (DOAC) or warfarin use prior to intracerebral hemorrhage
C
Comparator
Anticoagulant non-users matched by sex and age (±2 years)
O
Outcome
Cerebral small vessel disease (SVD) burden assessed by brain CT (CT-SVD score 0-3)surrogate

Main Result

Effect estimate: cOR 0.22 (95% CI 0.10-0.48)

Absolute Event Rate: 0% vs 2%

p-value: p=<0.001

This study investigates whether the burden of cerebral small vessel disease differs among patients presenting with spontaneous intracerebral hemorrhage who were previously treated with DOACs, warfarin, or no anticoagulation.

Limitations

  • Head CT is less sensitive than MRI for detecting microbleeds and superficial siderosis
  • Low CT-SVD burden scores in the supratherapeutic group may stem from coagulopathy masking microvascular contributions
  • Coarser granularity of CT-SVD compared with MRI
  • Data sparsity in small subgroups led to nominal violations of the proportional odds assumption
  • Cross-sectional design precludes assessing the influence of cumulative antithrombotic exposure

Cite This Study

Tang et al. (2026) conducted a cohort in Spontaneous intracerebral hemorrhage (n=384). Warfarin vs. Direct oral anticoagulants (DOAC) and anticoagulant non-users was evaluated on CT-evaluated small vessel disease (CT-SVD) burden score (cOR 0.22, 95% CI 0.10-0.48, p=<0.001). Warfarin users who experienced intracerebral hemorrhage demonstrated a significantly lower small vessel disease burden compared with DOAC users (cOR 0.22) and anticoagulant non-users.

synapsesocial.com/papers/6a1bd0155783ba022b6fbe3ahttps://doi.org/10.5853/jos.2025.05785
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