Early antiplatelet therapy after intravenous thrombolysis in acute non-cardiogenic ischemic stroke: a systematic review and meta-analysis

Background Intravenous thrombolysis (IVT) is a cornerstone of acute ischemic stroke management; however, early neurological deterioration due to reocclusion remains a concern, particularly in non-cardiogenic stroke where platelet-rich thrombi predominate. The safety and efficacy of early antiplatelet therapy (APT) initiated within 24 h after IVT in this specific population remain controversial. This meta-analysis evaluates the available evidence on early APT versus standard delayed APT, with particular attention to the type of antiplatelet agent used. Methods We systematically searched PubMed, Embase, and the Cochrane Library for studies published between January 2021 and March 2026, with a supplementary search conducted on May 15, 2026, evaluating early APT (≤24 h after IVT) versus standard APT (>24 h) in non-cardiogenic ischemic stroke. The primary efficacy outcome was favorable functional outcome (modified Rankin Scale score 0–1 at 90 days). The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Pre-specified RCT-only analyses were conducted as the primary analytic strategy, with observational studies included as supportive evidence. Results Four studies comprising 1,394 patients were included in the quantitative synthesis. In the two RCTs (ASSET-IT and INSTANT, n = 1,191), early tirofiban was associated with significantly higher odds of favorable functional outcome compared with standard APT (OR 1.78, 95% CI 1.38–2.30, p < 0.001, I 2 = 42%). We did not detect a statistically significant increase in sICH (OR 1.19, 95% CI 0.64–2.21, p = 0.59, I 2 = 0%) or 90-day mortality (OR 0.84, 95% CI 0.61–1.16, p = 0.29, I 2 = 0%). The combined analysis including observational studies yielded consistent results (favorable outcome: OR 1.72, 95% CI 1.38–2.15; sICH: OR 1.25, 95% CI 0.71–2.18; mortality: OR 0.86, 95% CI 0.64–1.16). Subgroup analysis suggested numerically greater efficacy with tirofiban-based regimens (OR 1.81) compared with aspirin (OR 1.35), though the interaction was not statistically significant ( p = 0.11). The evidence base predominantly concerns tirofiban, with only one small study evaluating aspirin. Conclusion In patients with acute non-cardiogenic ischemic stroke, early tirofiban administration within 24 h after intravenous thrombolysis significantly improves functional outcomes. We did not detect a statistically significant increase in symptomatic intracranial hemorrhage or mortality. However, the confidence intervals do not exclude a clinically meaningful increase in sICH risk, and the small number of hemorrhagic events limits the precision of these safety estimates. The evidence for aspirin and other antiplatelet agents remains very limited and requires further investigation. These findings support reconsideration of current guideline restrictions for selected patients, particularly regarding tirofiban-based regimens. Large-scale randomized controlled trials with standardized protocols are warranted to establish optimal timing, agent selection, dosing, and patient selection criteria.