{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T07:49:22Z","timestamp":1793260162818,"version":"4.5.0"},"reference-count":60,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"Importance<\/jats:title>Atrial fibrillation (AF) is a leading cause of stroke, and oral anticoagulants (OAC) reduce this risk. However, there are limited data on the residual risk of recurrent stroke in patients with AF.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the recurrent stroke risk in patients with AF by performing a systematic review and meta-analysis.<\/jats:p><\/jats:sec>Data Sources<\/jats:title>Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until January 2025.<\/jats:p><\/jats:sec>Study Selection<\/jats:title>Eligible studies enrolled patients with prior ischemic stroke and AF, reported information on incidence of recurrent stroke, and had follow-up data for 1 or more years. Three reviewers independently screened abstracts and performed full-text reviews.<\/jats:p><\/jats:sec>Data Extraction and Synthesis<\/jats:title>Data extraction was performed by 2 reviewers and independently verified by a third. Incidence rates were pooled using random-effects meta-analysis. Analysis was repeated in patients whose qualifying event occurred despite OAC. Study quality was assessed using the Quality In Prognosis Studies tool.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcome was recurrent ischemic stroke. The secondary outcomes were any recurrent stroke (ischemic stroke or intra-cerebral hemorrhage [ICH]) and ICH during follow-up.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 23 studies were identified, which included 78\u202f733 patients and 140\u202f307 years of follow-up. The median proportion of OAC use across studies was 92%. The pooled incidence of recurrent ischemic stroke was 3.75% per year (95% CI, 3.17%-4.33%). The risk was higher in noninterventional observational cohorts (4.20% per year; 95% CI, 3.41%-4.99%) compared with randomized clinical trials (2.26% per year; 95% CI, 1.96%-2.57%) (P<\/jats:italic> value for interaction &amp;lt;.001). The risk of any recurrent stroke was 4.88% per year (95% CI, 3.87%-5.90%), and the risk of ICH was 0.58% per year (95% CI, 0.43%-0.73%). In patients with stroke despite OAC, the risk was 7.20% per year (95% CI, 5.05%-9.34%) for ischemic stroke, 8.96% per year (95% CI, 8.25%-9.67%) for any stroke, and 1.40% per year (95% CI, 0.40%-2.40%) for ICH.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this systematic review and meta-analysis, even with modern prevention therapy, the residual recurrence risk after AF-related stroke is high, with an estimated 1 in 6 patients experiencing a recurrent ischemic stroke at 5 years. These data demonstrate an urgent need to improve our understanding of the biological processes responsible for recurrence, improve risk stratification, and develop new secondary prevention strategies after AF-related stroke.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.1337","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T02:30:19Z","timestamp":1747794619000},"page":"696","source":"Crossref","is-referenced-by-count":53,"title":["Residual Risk of Recurrent Stroke Despite Anticoagulation in Patients With Atrial Fibrillation"],"prefix":"10.1001","volume":"82","author":[{"given":"John J.","family":"McCabe","sequence":"first","affiliation":[{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin, Ireland"},{"name":"School of Medicine, University College Dublin, Dublin, Ireland"},{"name":"Stroke Service, Department of Geriatric Medicine, Mater Misericordiae University Hospital, Dublin, 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