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

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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Journal
Stroke
Published
2026-01-29
DOI
https://doi.org/10.1161/str.57.suppl_1.wp146
Primary Topic
Acute Ischemic Stroke Management
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article
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article

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

Wayneho Kam, Emiliya Melkumova, Setareh Salehi Omran, Franziska Herpich et al.
Stroke
Acute Ischemic Stroke Management
article

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

Wayneho Kam, Emiliya Melkumova, Setareh Salehi Omran, Franziska Herpich, Simona Nedelcu, Diana Rojas-Soto, Patrick A. Glover, Mahan Shahrivari, Hassan Aboul Nour, Dinesh V. Jillella, James Ernest Siegler, Collin J. Culbertson, Guillermo Linares, Kelsey Eklund, James R. Brorson, Alireza Borghei, Aaron Rothstein, Russell J. Van Coevering, Mark Smith, D Liebeskind, Farid Khasiyev, Mudassir Farooqui, Alicia Zha, Jesse Thon, Mary Penckofer, Christina Lineback, Shadi Yaghi, Richa Sharma, Sami Al Kasab, Deborah Kerrigan, Shani Mannion, Muhammad Alvi, Yasmin Aziz, Fadi Nahab, Adam de Havenon, Oana Dumitrascu, Marissa D'Souza, Thanh N. Nguyen
article en

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.

StrokeVol. 57(Suppl_1)
West Virginia University (US), University of Iowa (US), Christiana Care Health System (US), Boston Medical Center (US), Dartmouth–Hitchcock Medical Center (US), Tufts Medical Center (US), Emory University (US), Medical University of South Carolina (US), University of Tennessee Health Science Center (US), Duke University (US), Brown University (US), University of Michigan (US), UCLA Health (US), University of Minnesota System (US), Cooper University Hospital (US), Yale University (US), University of Chicago (US), Massachusetts General Hospital (US), Cooper Medical School of Rowan University (US), Lahey Medical Center (US), Michigan United (US), Emory Johns Creek Hospital (US), Mayo Clinic in Arizona (US), Saint Louis University (US), University of Colorado Anschutz Medical Campus (US), The Ohio State University (US), University of Cincinnati (US), University of Pennsylvania (US), Vanderbilt University Medical Center (US), The University of Texas Health Science Center at Houston (US), University of Colorado Denver (US), Brookhaven College (US)
Good health and well-being
Openalex Percentile: Top 72%
Acute Ischemic Stroke Management
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