Adjunctive Intravenous Tirofiban After Thrombolysis for Acute Ischemic Stroke

Background: Intravenous tirofiban, a short-acting reversible glycoprotein IIb/IIIa inhibitor, targets platelet-mediated re-thrombosis after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). Despite two recent phase 3 trials substantially expanding the evidence base, no tirofiban-specific meta-analysis incorporating contemporary data exists. Methods: A PRISMA-guided systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted by searching PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through May 2026, comparing adjunctive intravenous tirofiban initiated within 24 hours of IVT versus placebo or standard care in adults with AIS. The primary outcome was excellent functional status (modified Rankin Scale [mRS] 0-1 at 90 days). Dichotomous outcomes were pooled as risk ratios (RRs) using random-effects models. A pre-specified subgroup stratified by indication, prophylactic versus response-guided, was conducted to explore heterogeneity. GRADE certainty was assigned for each outcome. Results: Seven RCTs enrolling 1,869 patients (tirofiban n=1,011; control n=858; 2016-2026) were included. Adjunctive tirofiban significantly improved mRS 0-1 at 90 days (RR 1.23, 95% CI 1.11-1.37; I 2 =11%; GRADE moderate). The prophylactic subgroup, anchored by ASSET-IT 2025 and comprising three RCTs (n=1,134), demonstrated a consistent, heterogeneity-free benefit (RR 1.22, 95% CI 1.10-1.35; I 2 =0%). Functional independence (mRS 0-2; 6 RCTs) was similarly improved (RR 1.17, 95% CI 1.06-1.29; I 2 =46%; GRADE low). Symptomatic intracranial hemorrhage trended higher with tirofiban but did not reach significance (RR 1.81, 95% CI 0.66-5.00; I 2 =0%; GRADE low). Any intracranial hemorrhage did not differ (RR 1.14, 95% CI 0.76-1.70; I 2 =0%; GRADE low). Mortality was equivalent between groups (RR 0.97, 95% CI 0.52-1.82; I 2 =0%; GRADE low). Conclusions: Adjunctive intravenous tirofiban following IVT significantly improves excellent 90-day functional outcomes in AIS, with a consistent, heterogeneity-free effect in prophylactically treated patients and no significant increase in symptomatic hemorrhage or mortality. Driven by two adequately powered phase 3 trials, these findings support tirofiban as a clinically meaningful adjunct to IVT in noncardioembolic AIS. The sparse safety event data and predominantly Chinese evidence base necessitate geographically diverse confirmatory trials before universal adoption.