Pre-Procedural Tirofiban and First-Pass Reperfusion in Thrombectomy Stratified by Stroke Mechanism

Background: First-pass successful reperfusion (FPSR) is a key technical determinant of recovery after endovascular thrombectomy (EVT), yet pharmacologic strategies to increase it remain undefined. Glycoprotein IIb/IIIa inhibition with tirofiban before EVT is mechanistically attractive for platelet-rich atherosclerotic occlusions, but trial results have been inconsistent, and no synthesis has isolated its effect on FPSR or tested whether benefit depends on stroke mechanism. Methods: We performed a systematic review and meta-analysis of randomized trials comparing pre-procedural intravenous tirofiban with control in adults with acute anterior-circulation large-vessel occlusion undergoing EVT. The primary outcome was FPSR (successful reperfusion after a single device pass). Secondary outcomes were 90-day functional independence (modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and mortality. Risk ratios (RR) were pooled with random-effects models; prespecified subgroups distinguished atherosclerotic (intracranial atherosclerotic disease/large-artery atherosclerosis) from non-atherosclerotic occlusion. Results: Two randomized trials enrolling 1,240 patients were included; first-pass reperfusion was analyzable in 1,148 (FPSR data from one trial derived from a prespecified post hoc analysis). ; Tirofiban significantly increased FPSR (RR 1.31, 95% CI 1.11-1.55; P=0.001; I 2 =0%). The effect was numerically larger in atherosclerotic (RR 1.50, 95% CI 1.17-1.91) than in non-atherosclerotic occlusion (RR 1.11, 95% CI 0.86-1.43), although the interaction was not significant (P=0.09). Tirofiban did not improve 90-day functional independence overall (RR 0.87, 95% CI 0.63-1.20); however, a significant subgroup interaction (P=0.01) revealed divergent effects—neutral in atherosclerotic occlusion (RR 1.13, 95% CI 0.86-1.48) but reduced functional independence in non-atherosclerotic occlusion (RR 0.69, 95% CI 0.52-0.91). The sICH signal was inconsistent and statistically inconclusive (RR 0.47, 95% CI 0.02-9.14; I 2 =77%); mortality did not differ (RR 1.08, 95% CI 0.83-1.40). Conclusions: Pre-procedural tirofiban increases first-pass reperfusion during anterior-circulation thrombectomy, but this technical gain translates into functional outcomes only when the occlusion is atherosclerotic, with a signal of functional harm in non-atherosclerotic stroke. These hypothesis-generating findings argue that future phase 3 trials of adjunctive tirofiban should enrich for atherosclerotic large-vessel occlusion rather than an undifferentiated thrombectomy population.