Antiplatelet vs. Anticoagulant Therapy in Secondary Prevention of Ischemic Stroke: A Systematic Review and Meta-Analysis

Abstract

Background: Secondary prevention after ischemic stroke is critical to reduce recurrence and long-term disability. Antiplatelet therapy is recommended for non-cardioembolic stroke, while oral anticoagulation is standard for atrial fibrillation (AF)-related stroke. However, whether anticoagulants offer additional benefit over antiplatelets in other etiologies, particularly embolic stroke of undetermined source (ESUS), remains uncertain.

Objective: To compare the efficacy and safety of antiplatelet versus anticoagulant therapy for secondary prevention in patients with prior ischemic stroke or transient ischemic attack (TIA).

Methods: We systematically searched MEDLINE, Embase, CENTRAL, Web of Science, and trial registries up to September 2025. Eligible studies were randomized controlled trials comparing oral anticoagulants (warfarin or direct oral anticoagulants [DOACs]) with antiplatelets (single or dual therapy). Primary outcomes were recurrent ischemic stroke (efficacy) and major bleeding (safety). Random-effects meta-analysis was performed with Hartung-Knapp adjustment.

Results: Four RCTs were included, enrolling 15,378 participants: WARSS (non-cardioembolic), WASID (intracranial stenosis), NAVIGATE ESUS, and RE-SPECT ESUS.

• Recurrent ischemic stroke: No significant difference between anticoagulants and antiplatelets (pooled RR 1.02, 95% CI 0.91-1.14; I² = 0%).


• Major bleeding: Higher with anticoagulants compared to antiplatelets (pooled RR 1.62, 95% CI 1.21-2.16; I² = 22%).


• Subgroup analysis showed rivaroxaban significantly increased major bleeding, dabigatran had a neutral bleeding profile, and warfarin consistently increased bleeding risk.

Conclusions: In patients with ischemic stroke or TIA without atrial fibrillation, anticoagulation does not reduce recurrent ischemic stroke compared with antiplatelet therapy and increases major bleeding risk. Antiplatelets remain the preferred strategy in non-cardioembolic and ESUS subgroups, while anticoagulation should be reserved for AF-related stroke.