Comparative Efficacy and Safety of Dual Antiplatelet Therapy Strategies Defined by Drug Composition and Treatment Duration for Acute Minor Ischemic Stroke or High-Risk Transient Ischemic Attack: A Systematic Review and Bayesian Network Meta-Analysis

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Abstract

BACKGROUND: Dual antiplatelet therapy (DAPT) comprising aspirin and a P2Y₁₂ inhibitor is the cornerstone of early-phase secondary prevention after acute minor ischemic stroke or high-risk transient ischemic attack (TIA). Multiple regimens varying in drug combination and treatment duration are available, yet their comparative efficacy and safety profiles have not been fully elucidated. We performed a systematic review and Bayesian network meta-analysis to simultaneously compare all available DAPT strategies-defined jointly by drug and duration-in terms of ischemic stroke prevention, major bleeding risk, and net clinical benefit. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science from inception to April 2026 for randomized controlled trials enrolling adults with acute non-cardioembolic minor ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk TIA. Eligible interventions comprised aspirin monotherapy, clopidogrel plus aspirin for 21 or 90 days, ticagrelor plus aspirin for 21 or 30 days, and ticagrelor monotherapy, all initiated within 72 hours of symptom onset. The primary efficacy outcome was recurrent ischemic stroke at 90 days; the primary safety outcome was major bleeding. Bayesian random-effects network meta-analyses were conducted using Markov chain Monte Carlo methods. Treatment rankings were assessed with surface under the cumulative ranking curve (SUCRA) values, and benefit-risk balance was evaluated through cluster rank analysis. PROSPERO registration: [number would be inserted]. RESULTS: Eight trials encompassing 50,349 patients were included. Ticagrelor plus aspirin for 21 days achieved the greatest reduction in recurrent ischemic stroke compared with aspirin monotherapy (odds ratio [OR] 0.55, 95% credible interval [CrI] 0.46-0.66; SUCRA 0.92), followed by clopidogrel plus aspirin for 21 days (OR 0.68, 95% CrI 0.57-0.81; SUCRA 0.68). Clopidogrel plus aspirin for 21 days was the only DAPT strategy not associated with a significantly increased risk of major bleeding (OR 1.05, 95% CrI 0.70-1.58) and demonstrated the most favorable overall benefit-risk profile in cluster analysis. Ticagrelor plus aspirin for 21 days conferred the highest efficacy but at the expense of increased major bleeding (OR 1.80, 95% CrI 1.20-2.70). Ticagrelor plus aspirin for 30 days carried the greatest bleeding hazard (OR 2.10, 95% CrI 1.50-2.94). No significant inconsistency between direct and indirect evidence was detected, and findings were robust across sensitivity analyses and subgroups. CONCLUSIONS: Among patients with acute minor ischemic stroke or high-risk TIA, clopidogrel plus aspirin for 21 days provides the most favorable net clinical benefit for the majority of patients, whereas ticagrelor plus aspirin for 21 days offers maximal ischemic protection at a cost of increased bleeding and may be preferred in selected high-risk individuals. These findings support individualized antiplatelet therapy and reinforce the importance of jointly considering drug composition and treatment duration in clinical decision-making.

Abstract as published, via PubMed.