ABSTRACT NUMBER: ESOC2026A1849 EARLY ANTIPLATELET THERAPY AFTER INTRAVENOUS THROMBOLYSIS FOR ACUTE ISCHEMIC STROKE: A COMPREHENSIVE META ANALYSIS WITH TRIAL SEQUENTIAL ANALYSIS

Abstract Background and aims Early antiplatelet therapy (eAPT) after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients may prevent re-occlusion and early neurological deterioration, but it could increase hemorrhagic transformation. Evidence remains conflicting, particularly with emerging contemporary trials. Methods We conducted a PRISMA-guided systematic review of randomized controlled trials (RCTs) comparing eAPT initiated within 24 hours after IVT (with or without thrombectomy) versus standard timing (>24 h), placebo, or no antiplatelet therapy (CRD420251276445). Random-effects models were used to estimate odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs). Trial sequential analysis (TSA), subgroup analyses, meta-regression, and GRADE certainty ratings were performed. Results Twelve RCTs with 4,595 patients were included. eAPT led to higher non-significant odds of symptomatic intracranial hemorrhage (sICH) (OR 1.68, 95% CI 0.94–3.01; I2 10.4%; GRADE moderate), and mortality (OR 1.15, 0.83–1.58; I2 14.8%; GRADE moderate) but not intracranial hemorrhage (OR 1.01, 0.64–1.60; I2 52.6%; GRADE low). Functional outcomes were not improved: mRS 0–1 (OR 1.10, 0.83–1.46; I2 60.5%; GRADE low) and mRS 0–2 (OR 1.27, 0.89–1.80; I2 73.4%; GRADE very low). TSA indicated evidence remains inconclusive. Agent-specific subgroup analyses suggested higher sICH with aspirin (OR 2.13) and possible benefit for mRS 0–2 with tirofiban (OR 2.07). Conclusions Routine eAPT within 24 hours after IVT does not provide conclusive functional benefit and cannot exclude clinically meaningful hemorrhagic harm. Further adequately powered RCTs are needed to define whether any selected regimen -especially tirofiban- has a favorable risk-benefit profile. Conflict of interest Hamdy A. Makhlouf: nothing to disclose. Ahmed Harb: nothing to disclose. Moaz Elsayed Abouelmagd: nothing to disclose. Anas Mansour: nothing to disclose. Ahmed S.A. Osman: nothing to disclose. Nada Mosad: nothing to disclose. Ahmed H. Abdelaal: nothing to disclose. Omar Kassar: nothing to disclose. Dr. Saver reported receiving consulting fees from Biogen, Boehringer Ingelheim, Genentech, Johnson and Johnson, Phenox, Phillips, Rapid Medical, and Roche for advising on rigorous and safe clinical trial design and conduct outside the submitted work.