Adjunctive tirofiban for acute ischemic stroke undergoing reperfusion therapy: an updated systematic review and meta-analysis of randomized controlled trials

Background: Tirofiban has been investigated as an adjunctive therapy in acute ischemic stroke (AIS) patients undergoing reperfusion therapies. Although previous studies suggested improved functional outcomes, especially those undergoing intravenous thrombolysis (IVT), evidence has remained limited. We performed an updated systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of tirofiban as an adjunct to reperfusion therapies. Objective: To assess the effects of adjunctive tirofiban on functional outcomes, symptomatic intracranial hemorrhage (sICH), and all-cause mortality in AIS patients treated with IVT or endovascular thrombectomy (EVT). Methods: We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for RCTs comparing tirofiban plus standard reperfusion therapy versus standard therapy alone. The primary outcome was favorable functional outcome at 90 days (modified Rankin Scale [mRS] 0–2). Secondary outcomes included sICH and all-cause mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Prespecified subgroup analyses were performed according to reperfusion strategy (IVT or EVT). Results: Eleven RCTs including 4,482 patients were analyzed. Overall, adjunctive tirofiban significantly increased the likelihood of achieving favorable functional outcome at 90 days compared with standard treatment alone (RR 1.14, 95% CI 1.06–1.23). In subgroup analyses, the benefit was significant among patients receiving IVT (RR 1.17, 95% CI 1.06–1.29), whereas no statistically significant improvement was observed in the EVT subgroup. Tirofiban was not associated with an increased risk of symptomatic intracranial hemorrhage overall (RR 1.26, 95% CI 0.97–1.64), with consistent findings in both IVT (RR 1.17, 95% CI 0.65–2.09) and EVT (RR 1.27, 95% CI 0.85–1.90) subgroups. Likewise, all-cause mortality was similar between groups (RR 1.00, 95% CI 0.85–1.17), with no significant differences in either the IVT (RR 0.98, 95% CI 0.51–1.85) or EVT subgroup (RR 1.00, 95% CI 0.84–1.18). Conclusion: Adjunctive tirofiban improves 90-day functional outcomes in patients with AIS undergoing reperfusion therapy without increasing the risks of symptomatic intracranial hemorrhage or mortality. The functional benefit was statistically significant among IVT-treated patients, whereas the EVT subgroup showed a favorable trend without reaching statistical significance. These findings support the safety of tirofiban and suggest that its greatest clinical benefit may be observed when combined with IVT, although additional large-scale trials are warranted to clarify its role in EVT-treated patients.