Efficacy and safety of tirofiban for acute ischemic stroke without large and medium vessel occlusion: a systematic review and meta-analysis

Background Early and effective intervention is crucial in the management of acute ischemic stroke (AIS) without large- or medium-vessel occlusion (non-LVO/MVO), which accounts for approximately 60–70% of all AIS cases. Tirofiban has been investigated as a therapeutic option for non-LVO/MVO AIS. However, existing studies have reported inconsistent findings regarding its efficacy and safety, and high-level evidence derived from large-scale pooled analyses remains lacking. Aims This study aimed to conduct a systematic review and meta-analysis to assess the efficacy and safety of tirofiban in patients with non-LVO/MVO AIS, and to further explore the influence of intravenous thrombolysis (IVT) status and study design on treatment outcomes. Summary of review PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched from inception to December 2025. Eligible studies included patients with non-LVO/MVO AIS, compared tirofiban with conventional antiplatelet therapy, and reported original data on functional or safety outcomes. The primary efficacy outcomes were excellent functional outcome at 90 days (modified Rankin Scale mRS score 0–1) and favorable functional outcome (mRS score 0–2). Safety outcomes included symptomatic intracerebral hemorrhage (sICH), 90-day mortality, and peripheral bleeding. Subgroup analyses were conducted according to IVT status and study design. A total of 1,678 records were identified, of which nine studies met the inclusion criteria, encompassing 3,225 patients. Tirofiban was associated with a significantly higher likelihood of achieving a 90-day excellent functional outcome (odds ratio OR 1.66, 95% confidence interval CI 1.34–2.06; p 0.001; I 2 = 26%) and favorable functional outcome (OR 1.79, 95% CI 1.30–2.47; p 0.001; I 2 = 58%). Regarding safety, tirofiban did not significantly increase the risk of sICH (OR 4.02, 95% CI 0.91–17.70; p = 0.07; I 2 = 5%) or 90-day mortality (OR 1.06, 95% CI 0.53–2.12; p = 0.87; I 2 = 37%). However, it was associated with a significantly higher risk of peripheral bleeding (OR 1.87, 95% CI 1.32–2.66; p 0.001; I 2 = 0%). Subgroup analyses demonstrated tirofiban conferred significant functional benefits exclusively in non-IVT patients, whereas no such improvement was observed in patients with prior IVT. However, particularly robust and homogeneous effects observed in the randomized controlled trial (RCT) subgroup ( I 2 = 0% for mRS 0–1). Conclusion Tirofiban significantly improves 90-day functional outcomes in patients with non-LVO/MVO acute ischemic stroke, with primarily observed in patients without prior IVT. The clinical utility of adding tirofiban post-IVT remains unproven. Although its use was not associated with an increased risk of severe bleeding or mortality, the higher incidence of peripheral bleeding warrants careful monitoring in clinical practice.