Small Vessel Disease Increases Risk of Ischemic Stroke

David J. Werring, PhD, FRCP

This article, "Oral Anticoagulation for AFib Insufficient After Ischemic Stroke in Patients with SVD," was originally published in NeurologyLive.

New data shows small vessel disease (SVD) is associated with an increased risk of recurrent ischemic stroke (IS) during follow-up for patients treated with anticoagulation for atrial fibrillation (AFib) after ischemic stroke or transient ischemic attack (TIA).

The IS rate during follow-up in patients with any SVD was 2.20 per 100 patient years (95% CI, 1.60–3.02), compared to 0.98 per 100 patient years (95% CI, 0.59–1.62) in patients without SVD.

Senior author David J. Werring, PhD, FRCP, Professor of Clinical Neurology and Honorary Consultant Neurologist, Stroke Research Centre, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, University College Hospitals NHS Foundation Trust, and colleagues wrote that “Our data did not demonstrate that baseline SVD is associated with the subtype of recurrent IS.

“However, the absolute rate of recurrent small artery occlusion in patients with baseline SVD was higher than in those without SVD... One possible explanation is that SVD is associated with risk factors for atherosclerosis, which are known predictors of stroke recurrence.”

Werring and colleagues analyzed data from 1419 patients enrolled in CROMIS-2 (Clinical Relevance of Microbleeds in Stroke Study), a prospective multicenter inception cohort study of IS or TIA anticoagulated for AFib.

These patients had a mean age of 75.8 years (standard deviation [SD], 10.4) and were 42.1% female. SVD was present in 768 (54.1%) of patients.

Individual SVD markers were assessed and ≥11 basal ganglia perivascular spaces (BGPVS) were present in 375 (26.4%) patients; ≥11 centrum semiovale perivascular spaces were present in 681 (48%) patients; cerebral microbleeds (CMBs) were present in 298 (21%) patients; lacunes in 295 (20.8%) patients; and moderate to severe white matter hyperintensities (WMH) were present in 283 (19.9%) patients.

Werring and colleagues found that patients that experienced IS during follow-up had a median CHA2DS2-VASc score of 6 (interquartile range [IQR], 5–7) versus patients who did not that had a median score of 5 (IQR, 4–6). Age (HR, 1.04; 95% CI, 1.01–1.07), female sex (HR, 2.01; 95% CI, 1.17–3.48), diabetes (HR, 2.11; 95% CI, 1.16–3.84), and vascular disease (HR, 2.24; 95% CI, 1.26–3.99) were associated with IS during follow-up.

Patients with ≥11 BGPVS were also more likely to experience a recurrent IS independent of SVD score. With ≥11 BGPVS, the IS event rate during follow-up was 2.98 per 100-patient years (95% CI, 1.99–4.44), compared to 1.18 per 100-patient years (95% CI, 0.82–1.70) in patients with ≤11 BGPVS. This association remained significant after adjusting for CHA2DS2-VASc Score but no other SVD markers were significantly associated with recurrent IS risk.

The absolute rate increase associated with SVD presence was 1.22 per 100 patient-years (95% CI, 1.01–1.40). Recurrent IS was more frequent in patients with SVD presence compared with those without SVD presence according to Kaplan-Meier analysis (log-rank test, P = .008). In univariate Cox regression analysis, patients with SVD had a 2.2-times higher risk of IS during follow-up (95% CI, 1.21–4.01; P = .009).

“Preventing recurrent IS in stroke or TIA patients with AFib and SVD requires better management options... Our findings suggest that oral anticoagulation (OAC) is not as effective in patients with AFib who have SVD as it is in those without; this patient group should be a focus for trials of new prevention strategies,” Werring and colleagues concluded.