IMPORTANCE: 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.
OBJECTIVE: To determine the recurrent stroke risk in patients with AF by performing a systematic review and meta-analysis.
DATA SOURCES: Eligible studies were identified by searching Ovid MEDLINE and Embase from inception (Ovid: January 1946; Embase: January 1970) until January 2025.
STUDY SELECTION: 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.
DATA EXTRACTION AND SYNTHESIS: 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.
MAIN OUTCOMES AND MEASURES: 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.
RESULTS: A 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%) (P value for interaction <.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.
CONCLUSIONS AND RELEVANCE: 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.
| Discipline Area | Score |
|---|---|
| Internal Medicine |  |
| Cardiology | |
| Neurology | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) | |
Very interesting data opening the road to future studies designed to answer the question on how to stratify and reduce the residual risk of stroke in patients with AF on OAC.
This is very important work. Many doctors and even more patients overestimate the effects of various therapies in the sense of an assurance: “if I take anticoagulation, then I can no longer have a stroke.” This study clears up this misconception: if one in only 6 patients with atrial fibrillation has to expect a stroke in the coming years despite anticoagulation, this is a considerable magnitude. This information should be included in the patient information prior to the joint decision for or against anticoagulation.
These are great numbers to have in hand when speaking with patients; however, the only caveats are the extreme heterogeneity in the summary estimates (>95%) and the presence of small study effects (publication bias), which really temper the reliability of the estimates.
