Abstract 4370605: Early versus Late Initiation of Anticoagulation in Acute Ischemic Stroke With or Without Atrial Fibrillation: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis

Background: The optimal timing of anticoagulation following acute ischemic stroke remains debatable, particularly in patients with or without atrial fibrillation (AF), where balancing thromboembolic prevention against bleeding risk is critical for clinical decision-making. Research Question: What is the comparative safety and efficacy of early versus delayed anticoagulation initiation in patients with acute ischemic stroke, stratified by the presence or absence of AF ? Methods: A comprehensive search identified randomized controlled trials (RCTs) and observational studies for inclusion. Pairwise meta-analyses were conducted using a random-effects model in RevMan. Trial Sequential Analysis (TSA) was performed in R to assess statistical reliability, assuming a 5% alpha and 90% power. Results: We included 21 studies comprising 23,676 patients, stratified by anticoagulation indication (AF vs. non-AF). In patients with AF, early anticoagulation significantly reduced the risk of post-intervention stroke by 27% (OR: 0.73; 95% CI: 0.62–0.87). In patients without AF, stroke risk reduction was 64% (OR: 0.36; 95% CI: 0.10–1.34), though not statistically significant. Overall, early anticoagulation was associated with a 28% reduction in stroke risk (OR: 0.72; 95% CI: 0.61–0.86). Intracranial hemorrhage was significantly lower in the AF subgroup (OR: 0.67; 95% CI: 0.48–0.94), consistent with the overall analysis. No significant differences were observed in extracranial bleeding across subgroups. Early anticoagulation also significantly reduced systemic embolism risk overall by 37% (OR: 0.63; 95% CI: 0.42–0.95), though subgroup effects did not reach statistical significance. All-cause mortality did not differ significantly between early and delayed anticoagulation across all populations (AF: OR: 0.98; p = 0.82; non-AF: OR: 0.21; p = 0.07; overall: OR: 0.96; p = 0.67). TSA confirmed conclusive evidence for post-intervention stroke, as the Z-curve crossed the monitoring boundary. However, for all-cause mortality, intracranial hemorrhage, systemic embolism, and extracranial bleeding, the Z-curves did not cross monitoring boundaries nor reach required information sizes, indicating insufficient evidence and the need for further trials. Conclusion: Early anticoagulation after ischemic stroke reduces post-stroke events, especially in patients with AF, without increasing bleeding risk. Further trials are needed to confirm effects on mortality and systemic embolism.