Introduction: Stroke is a leading cause of disability and the second leading cause of death worldwide. Despite guideline-recommended intravenous thrombolysis within four and a half hours (with mechanical thrombectomy when indicated), durable reperfusion is inconsistent and early re-occlusion is common, while immediate antiplatelet use is limited by hemorrhage risk. Tirofiban, a short-acting glycoprotein IIb/IIIa inhibitor, may stabilize patency in this window. We synthesized randomized evidence to determine whether adjunct tirofiban after intravenous thrombolysis improves ninety-day functional outcomes without increasing bleeding or mortality. Methods: Randomized controlled trials enrolling adults with acute ischemic stroke treated within 4.5 hours were identified in MEDLINE (via PubMed), Scopus, Web of Science, and the Cochrane Library from inception to August 2025. Trials compared tirofiban plus IVT with IVT alone. Random-effects models produced risk ratios (RRs) or mean differences (MDs) with 95% confidence intervals (CIs); heterogeneity was quantified with I2. Primary outcomes were excellent function (modified Rankin Scale mRS 0–1) and functional independence (mRS 0–2) at 90 days. Safety outcomes were intracranial hemorrhage (ICH), systemic bleeding, and mortality. Results: The final analysis included three RCTs (n = 1132). The pooled analysis showed that adjunct tirofiban after intravenous thrombolysis significantly increased excellent functional status at 90 days RR 1.19, 95% CI (1.07; 1.33), P = 0.002 and functional independence RR 1.20, 95% CI (1.04; 1.38), P = 0.01, while reducing poor functional outcome RR 0.61, 95% CI (0.46; 0.81), P = 0.0006. Moreover, early neurological improvement at 24–72 hours significantly favored tirofiban MD −0.70, 95% CI (−1.12; −0.27), P = 0.001. However, there was no significant difference in NIHSS score at 5–7 days MD −1.37, 95% CI (−3.69; 0.95), P = 0.25. Safety outcomes were comparable between groups: any intracranial hemorrhage RR 1.38, 95% CI (0.79; 2.40), P = 0.26, symptomatic ICH RR 2.28, 95% CI (0.05; 110.42), P = 0.68, systemic bleeding RR 1.16, 95% CI (0.45; 2.98), P = 0.75, and 90-day mortality RR 1.07, 95% CI (0.55; 2.09), P = 0.84. Conclusions: Across randomized trials, adjunct tirofiban after IVT improved ninety-day functional outcomes without a detectable increase in hemorrhage or death. Larger, multicenter trials are warranted to refine timing, dosing, and selection of candidates.
Gadelmawla et al. (Thu,) studied this question.