Small vessel disease and ischemic stroke risk during anticoagulation for atrial fibrillation after cerebral ischemia

Du, H. et al. (2020) Small vessel disease and ischemic stroke risk during anticoagulation for atrial fibrillation after cerebral ischemia. Stroke, 52, pp. 91-99. (doi: 10.1161/STROKEAHA.120.029474) (PMID:33280548)

Abstract

Background and Purpose: The causes of recurrent ischemic stroke despite anticoagulation for atrial fibrillation are uncertain but might include small vessel occlusion. We investigated whether magnetic resonance imaging markers of cerebral small vessel disease (SVD) are associated with ischemic stroke risk during follow-up in patients anticoagulated for atrial fibrillation after recent ischemic stroke or transient ischemic attack. Methods: We analyzed data from a prospective multicenter inception cohort study of ischemic stroke or transient ischemic attack anticoagulated for atrial fibrillation (CROMIS-2 [Clinical Relevance of Microbleeds in Stroke Study]). We rated markers of SVD on baseline brain magnetic resonance imaging: basal ganglia perivascular spaces (number ≥11); cerebral microbleeds (number ≥1); lacunes (number ≥1); and white matter hyperintensities (periventricular Fazekas grade 3 or deep white matter Fazekas grade ≥2). We investigated the associations of SVD presence (defined as presence of ≥1 SVD marker) and severity (composite SVD score) with the risk of ischemic stroke during follow-up using a Cox proportional hazards model adjusted for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score. Results: We included 1419 patients (mean age: 75.8 years [SD, 10.4]; 42.1% female). The ischemic stroke rate during follow-up in patients with any SVD was 2.20 per 100-patient years (95% CI, 1.60–3.02), compared with 0.98 per 100 patient-years (95% CI, 0.59–1.62) in those without SVD (P=0.008). After adjusting for congestive heart failure, hypertension, age >75, diabetes, stroke, vascular disease, age 65–74, female score, SVD presence remained significantly associated with ischemic stroke during follow-up (hazard ratio, 1.89 [95% CI, 1.01–3.53]; P=0.046); the risk of recurrent ischemic stroke increased with SVD score (hazard ratio per point increase, 1.33 [95% CI, 1.04–1.70]; P=0.023). Conclusions: In patients anticoagulated for atrial fibrillation after ischemic stroke or transient ischemic attack, magnetic resonance imaging markers of SVD are associated with an increased risk of ischemic stroke during follow-up; improved stroke prevention treatments are required in this population. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02513316.

• Item Type: Articles
• Additional Information: The CROMIS-2 (Clinical Relevance of Microbleeds in Stroke Study) is funded by the Stroke Association and the British Heart Foundation. Dr Du was supported by Fujian Provincial Natural and Science Innovation Project (No. 2016B014), Fujian Fumin Foundation. Dr Ambler receives funding from the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Center. G. Banerjee holds an NIHR Academic Clinical Fellowship and receives funding from the Rosetrees Trust. T. Yousry reports grants from the UK Medical Research Council, MS Society of Great Britain and Northern Ireland, Stroke Association, British Heart Foundation, and Wellcome Trust. Dr Al-Shahi Salman is funded by an MRc senior clinical fellowship. Dr Werring receives research support from the Stroke Association, the British Heart Foundation, and the Rosetrees Trust.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith
• Authors: Du, H., Wilson, D., Ambler, G., Banerjee, G., Shakeshaft, C., Cohen, H., Yousry, T., Al-Shahi Salman, R., Lip, G. Y.H., Houlden, H., Brown, M. M., Muir, K. W., Jäger, H. R., and Werring, D. J.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Stroke
• Publisher: American Heart Association
• ISSN: 0039-2499
• ISSN (Online): 1524-4628