Residual Risk of Recurrent Stroke Despite Anticoagulation in Patients With Atrial Fibrillation

ImportanceAtrial 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.ObjectiveTo determine the recurrent stroke risk in patients with AF by performing a systematic review and meta-analysis.Data SourcesEligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until January 2025.Study SelectionEligible 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.Data Extraction and SynthesisData 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.Main Outcomes and MeasuresThe 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.ResultsA total of 23 studies were identified, which included 78 733 patients and 140 307 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%) (Pvalue for interaction Conclusions and RelevanceIn 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.