Comparative Role of Antiplatelet and Anticoagulant Agents in Preventing Recurrent Ischemic Stroke: A Systematic Review and Meta-Analysis

Abstract

Background: Recurrent ischemic stroke remains a major cause of mortality and disability despite advances in acute management. Antiplatelet and anticoagulant agents are the cornerstone of secondary prevention, but their relative efficacy and safety in different stroke subtypes remain debated.

Objective: To compare the efficacy and safety of antiplatelet versus anticoagulant therapy for secondary prevention of ischemic stroke through a systematic review and meta-analysis.

Methods: A comprehensive search of PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov was performed for studies published between January 2000 and September 2025. Randomized controlled trials and cohort studies comparing antiplatelet and anticoagulant therapy in adults with prior ischemic stroke or transient ischemic attack were included. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a random-effects model following PRISMA 2020 guidelines.

Results: Fifteen studies involving 52,386 participants (antiplatelet = 27,031; anticoagulant = 25,355) met inclusion criteria. Overall, there was no significant difference in recurrent ischemic stroke between therapies (RR = 0.91; 95% CI 0.80-1.05; I² = 22%). In cardioembolic stroke subgroups, anticoagulants reduced recurrence risk (RR = 0.74; 95% CI 0.61-0.90), whereas outcomes were comparable in non-cardioembolic stroke (RR = 0.88; 95% CI 0.76-1.03). Major bleeding was significantly higher with anticoagulants (RR = 1.63; 95% CI 1.29-2.04), while mortality did not differ between groups (RR = 1.02; 95% CI 0.89-1.17).

Conclusion: Anticoagulant therapy provides superior protection against recurrent stroke in cardioembolic populations but carries an increased bleeding risk, whereas antiplatelet agents remain safer and equally effective for non-cardioembolic stroke. Individualized therapy selection based on stroke mechanism and bleeding risk is essential for optimal secondary prevention.