Efficacy and safety of adjunctive tirofiban administration in anterior large vessel occlusion due to large artery atherosclerosis: an individual patient data pooled analysis of two randomized clinical trials

Background: The role of different adjunctive tirofiban administration routes during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) due to large artery atherosclerosis (LAA) remains controversial. We evaluated the efficacy and safety of intravenous (IV) alone and combined intra-arterial and intravenous (IA + IV) tirofiban in in patients with LAA-related AIS. Methods: This individual patient data pooled analysis included 850 anterior circulation large vessel occlusion (LVO) patients due to LAA from two Chinese randomized trials (RESCUE BT and MARVEL). Patients were categorized into three groups: EVT alone (n = 360), Tirofiban-IV (n = 385), and Tirofiban-(IA + IV) (n = 105). Primary outcome was 90-day functional independence (modified Rankin Scale mRS 0–2). Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours, any ICH, and 90-day mortality. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used for baseline adjustment. Results: Among 850 eligible patients included in this analysis, the median age was 66 years, and 70.9% (n = 603) were male. Both tirofiban regimens were associated with improved functional independence compared to EVT alone: Tirofiban-IV group (51.9% vs. 37.2%; adjusted odds ratio aOR = 1.90, 95% CI 1.39-2.59; p < 0.01) and Tirofiban-(IA + IV) group (46.7% vs. 37.2%; aOR = 1.97, 95%CI 1.22-3.17; p < 0.01). Notably, both tirofiban strategies enhanced successful recanalization rates (expanded Thrombolysis in Cerebral Infarction eTICI ≥ 2b). The Tirofiban-IV group achieved 92.5% versus 83.3% in the EVT-alone group (aOR = 2.43, 95% CI 1.51-3.92; p < 0.01), with comparable efficacy in the Tirofiban-(IA + IV) group (91.4% vs. 83.3%; aOR = 2.47, 95%CI 1.15-5.30; p = 0.02). Moreover, neither the Tirofiban-IV group (sICH: aOR = 0.75, 95% CI 0.44-1.27, p = 0.29; mortality: aOR = 0.77, 95% CI 0.52-1.14, p = 0.20) nor the Tirofiban-(IA + IV) group (sICH: aOR = 0.49, 95% CI 0.20-1.23, p = 0.13; mortality: aOR = 0.64, 95% CI 0.35-1.18, p = 0.15) showed increased risks of sICH or mortality compared to the EVT-alone group. These results remained robust in PSM sensitivity analyses. Conclusions: In patients with anterior circulation LVO secondary to LAA undergoing EVT, adjunctive tirofiban, whether administered IV or via a combined IA + IV approach, was associated with superior 90-day functional outcomes and enhanced recanalization efficacy, without an increased risks of sICH or mortality.