Adjunctive Intra-Arterial Alteplase After Mechanical Thrombectomy in Acute Ischemic Stroke

Introduction: Adjunctive intra-arterial alteplase (IAT) is increasingly administered after successful endovascular thrombectomy (EVT) in acute ischemic stroke with large vessel occlusion (AIS-LVO), targeting residual microvascular thromboemboli beyond the reach of mechanical retrieval; however, its comparative efficacy and safety across anterior and posterior circulation remain uncertain, with no consensus on whether benefit is territory-dependent. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing adjunctive IAT (alteplase 0.225 mg/kg; maximum 22.5 mg, administered intra-arterially) versus control after successful EVT (eTICI ≥2b50) in adults with AIS-LVO was conducted by searching MEDLINE, Embase, and Cochrane CENTRAL through May 2026. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using random-effects models; heterogeneity was assessed with I 2 and χ 2 statistics. Analyses were performed with RevMan 5.4. Results: Four RCTs including 1,114 patients (IAT = 562; control = 552) were analysed. A pre-specified subgroup interaction by vascular territory was significant (P=0.027; I 2 =79.6%). In anterior circulation AIS-LVO (CHOICE 2022, PEARL 2025, CHOICE-2 2026; n=868), adjunctive IAT significantly improved excellent functional outcome (modified Rankin Scale [mRS] 0-1 at 90 days; RR 1.40, 95% CI 1.21-1.63; I 2 =0%; moderate certainty) and functional independence (Barthel Index ≥95; RR 1.05, 95% CI 0.93-1.18; I 2 =0%) compared with control. No benefit was identified in posterior circulation stroke (IAT-TOP 2026, basilar artery occlusion; RR 0.94, 95% CI 0.69-1.30; I 2 =N/A; P=0.72). Symptomatic intracranial haemorrhage (RR 0.92, 95% CI 0.43-1.97; I 2 =0), all-cause mortality (RR 1.26, 95% CI 0.85-1.86; I 2 =42%), and any intracranial haemorrhage (RR 1.15, 95% CI 0.92-1.43; I 2 =0%) did not differ significantly between groups. Conclusion: Adjunctive intra-arterial alteplase represents an effective post-thrombectomy strategy in anterior circulation AIS-LVO, significantly improving excellent 90-day functional outcome without excess haemorrhage or mortality (moderate certainty). No benefit was identified in posterior circulation stroke, establishing a clinically significant territory-dependent treatment effect. These findings support adjunctive IAT in appropriately selected patients with anterior circulation large vessel occlusion, though the significant heterogeneity in vascular territory response and moderate certainty of evidence warrant cautious interpretation and further confirmatory trials.