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

Abstract

Background: Ischemic stroke accounts for ~85% of all strokes and carries a high risk of recurrence despite secondary prevention. While antiplatelet agents are standard for non-cardioembolic stroke and anticoagulants are established in atrial fibrillation (AF), the optimal therapy for embolic stroke of undetermined source (ESUS) and other subtypes remains uncertain.

Methods: We performed a systematic review and meta-analysis (PRISMA 2020 compliant) of randomized controlled trials (RCTs) comparing oral anticoagulation (warfarin or direct oral anticoagulants [DOACs]) with antiplatelet therapy in adults with ischemic stroke or transient ischemic attack. Primary outcomes were recurrent ischemic stroke and major bleeding. Risk ratios (RRs) were pooled using a random-effects model.

Results: Four RCTs (WARSS, WASID, NAVIGATE ESUS, RE-SPECT ESUS) involving 15,378 participants were included. Anticoagulation did not significantly reduce recurrent ischemic stroke compared with antiplatelet therapy (RR 1.02; 95% CI, 0.91–1.14; I² = 0%). However, anticoagulation was associated with a significantly increased risk of major bleeding (RR 1.62; 95% CI, 1.21–2.16; I² = 22%). Subgroup analyses showed consistent results across ESUS and non-cardioembolic populations.

Conclusions: In patients without AF, anticoagulant therapy offers no added benefit over antiplatelet therapy for secondary prevention of ischemic stroke and confers a higher bleeding risk. Antiplatelets should remain the mainstay of therapy for non-cardioembolic and ESUS populations, whereas anticoagulation should be reserved for patients with confirmed cardioembolic mechanisms. Future trials should focus on identifying subgroups (e.g., atrial cardiopathy, covert AF) that may benefit from anticoagulation.