Ultra-early tirofiban after failed tenecteplase in branch atheromatous disease: efficacy and safety

Branch atheromatous disease (BAD), a common acute ischemic stroke subtype with high progression and recurrence risk, often shows limited improvement following intravenous thrombolysis. The glycoprotein IIb/IIIa antagonist tirofiban combined with tenecteplase (TNK) may enhance recanalization. This multicenter retrospective analysis included 1025 patients with BAD who completed intravenous TNK thrombolysis without symptomatic relief between September 2022 and 2025. Patients were assigned to tirofiban ( n = 309) or control ( n = 716) groups, according to ultra-early tirofiban administration. In the primary IPTW-weighted analysis, ultra-early tirofiban administration was significantly associated with a higher proportion of patients achieving 90-day modified Rankin Scale (mRS) ≤ 1( 63.4% vs. 42.7%; IPTW-weighted OR = 2.44, 95% CI: 1.82–3.28, P < 0.001) and mRS ≤ 2 (71.8% vs. 57.7%; IPTW-weighted OR = 2.00, 95% CI: 1.47–2.72, P < 0.001). Supportive sensitivity analyses using propensity score matching (256 pairs) yielded consistent findings (mRS ≤ 1: 62.5% vs. 44.5%, aOR: 1.404, 95% CI: 1.104–1.785, P = 0.006). Regarding safety endpoints, symptomatic intracranial hemorrhage (sICH) occurred in five (1.6%) tirofiban-treated and three (0.4%) control patients in the IPTW analysis (IPTW-weighted OR = 5.06, 95% CI: 0.64–40.19, P = 0.125), and 90-day mortality was 2.9% vs. 2.0% (IPTW-weighted OR = 1.65, 95% CI: 0.68–4.00, P = 0.263). Although no statistically significant differences were observed, the low number of safety events results in wide confidence intervals; thus, the safety of ultra-early tirofiban cannot be definitively established based on the current analysis, and an increased risk of sICH cannot be excluded.