What question did this study set out to answer?

This research aims to investigate the relationship between white matter disease and the risk of recurrent ischemic stroke in patients with ESUS, evaluating the influence of anticoagulation.

February 2, 2026Stroke0 citations

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Abstract WP146: White Matter Disease and Recurrent Stroke in ESUS: A Propensity-Weighted Analysis from the CASPR Registry

FKFarid KhasiyevUniversity of Minnesota ABAlireza BorgheiUniversity of Chicago MDMarissa D'SouzaUniversity of Michigan

Key Points

This research aims to investigate the relationship between white matter disease and the risk of recurrent ischemic stroke in patients with ESUS, evaluating the influence of anticoagulation.
Conducted a secondary analysis of the CASPR registry data from 27 centers.
Graded white matter disease severity using the Fazekas scale based on MRI findings.
Applied inverse probability of treatment weighting to adjust for baseline differences.
Utilized Cox proportional hazards models to assess associations between white matter disease and stroke outcomes.
Performed subgroup analyses for age, risk factors, and treatment type.
In the cohort of 1,890 ESUS patients, 684 (36.2%) had moderate-to-severe white matter disease (Fazekas 2-3).
Recurrent ischemic stroke occurred at a higher rate in patients with moderate-to-severe WMD (7.1% vs. 4.6% per year, HR 1.56).
No significant differences in major bleeding and mortality rates were observed between WMD groups.
Subgroup analyses revealed consistent risk of recurrent stroke regardless of age or treatment type.

Abstract

Background: Embolic stroke of undetermined source (ESUS) comprises infarct mechanisms presumed to be embolic and non-lacunar. One explanation for the lack of superiority of anticoagulation over aspirin is the inclusion of subcortical infarcts with white matter disease (WMD), reflecting small vessel pathology. We hypothesized that WMD is associated with recurrent ischemic stroke (RIS) in ESUS and this risk is not lessened by anticoagulation. Methods: We conducted a secondary analysis of the multicenter Cardiac Abnormalities in Stroke Prevention and Recurrence (CASPR) registry, including ESUS patients from 27 U.S. centers (2015–2024). WMD severity was graded using the Fazekas scale from MRI and dichotomized as mild (0–1) vs. moderate-to-severe (2–3). The primary outcome was RIS. Secondary outcomes were major bleeding and all-cause mortality. Inverse probability of treatment weighting (IPTW) adjusted for baseline differences. Cox proportional hazards models assessed associations between WMD and outcomes. Subgroup analyses explored effect modification by age, risk factors, and treatment type. Results: Among 1,890 ESUS patients with MRI data, 684 (36.2%) had Fazekas 2–3. These patients were older with more vascular risk factors, but IPTW achieved covariate balance. In the weighted cohort, RIS occurred more frequently in Fazekas 2–3 vs. 0–1 (7.1% vs. 4.6%/year; HR 1.56, 95% CI 1.10–2.22, p = 0.01). Major bleeding and mortality were similar (bleeding: 1.7% vs. 1.8%/yr, HR 0.96, p = 0.92; death: 7.0% vs. 6.7%/yr, HR 1.04, p = 0.81). Subgroup analyses showed no interaction between WMD and age, vascular risk factors, or treatment type (antiplatelet vs. anticoagulation), suggesting consistent RIS risk in those with higher WMD. Discussion: Moderate-to-severe WMD identifies ESUS patients at higher risk of ischemic stroke recurrence, with no mitigation by anticoagulation. These findings suggest that WMD may indicate non-embolic mechanisms and support the use of imaging-based risk stratification in ESUS.

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Cite This Study

Khasiyev et al. (Thu,) studied this question.

synapsesocial.com/papers/6980fd18c1c9540dea80ee1d https://doi.org/https://doi.org/10.1161/str.57.suppl_1.wp146

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