Efficacy and safety of low-dose tirofiban plus dual antiplatelet therapy in acute cerebral infarction beyond the thrombolysis window: a non-randomized trial with preliminary findings.

Abstract

Optimal antithrombotic strategies for patients with acute cerebral infarction beyond the thrombolysis window (6-24 h) without large or medium-sized vessel occlusion remain uncertain. This study evaluated the efficacy and safety of low-dose tirofiban combined with dual antiplatelet therapy (DAPT) in this population. This single-center, retrospective, non-randomized study enrolled 229 patients. The tirofiban group (n = 114) received low-dose tirofiban (0.1 µg/kg/min for 24 h) followed by DAPT, while the control group (n = 115) received DAPT alone. Inverse probability of treatment weighting (IPTW) balanced baseline covariates. The primary outcome was favorable functional outcome (modified Rankin Scale score 0-2) at 90 days. Secondary outcomes included excellent functional outcome (mRS 0-1 at 90 days), NIHSS improvement (≥ 3 points from baseline to 72 h) and early neurological deterioration (END). Safety outcomes included bleeding and symptomatic intracranial hemorrhage (sICH). Sensitivity analyses and E-values were calculated. After IPTW, all baseline covariates achieved excellent balance (all SMDs < 0.1). The primary outcome showed no significant difference between groups (OR = 0.41, 95% CI: 0.12-1.38, P = 0.151). However, tirofiban was associated with significantly higher odds of excellent functional outcome (mRS 0-1) (OR = 2.01, 95% CI: 1.07-3.77, P = 0.031) and NIHSS improvement (OR = 2.57, 95% CI: 1.42-4.66, P = 0.002). No significant differences were observed in END, bleeding, or sICH. Sensitivity analyses confirmed the robustness of tirofiban's benefit for both outcomes, with E-values of 4.58 and 3.43, respectively. Low-dose tirofiban combined with DAPT significantly improved early neurological recovery and excellent functional outcome without increasing bleeding or sICH risk. Although the primary outcome did not reach statistical significance, consistent sensitivity analyses support the clinical value of tirofiban. Larger randomized controlled trials are warranted.