The Added Benefit of Intra‐Arterial Thrombolysis After Successful Recanalization by Endovascular Treatment: A Systematic Review and Meta‐Analysis of Randomized‐Controlled Clinical Trials

BACKGROUND: Despite successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) with large-vessel occlusion (LVO), many patients fail to achieve excellent functional outcomes. Post-EVT intra-arterial thrombolysis (IAT) has emerged as a potential adjunctive strategy to improve microvascular reperfusion and clinical recovery. METHODS: We conducted a systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) comparing IAT plus best medical therapy (BMT) versus BMT alone in LVO-AIS patients with successful recanalization post-EVT. The primary efficacy outcome was 3-month excellent functional outcome modified Rankin Scale (mRS)-score: 0-1. Secondary efficacy outcomes included good functional outcome (mRS-score: 0-2) and reduced disability (mRS-score shift analysis) at 3 months. The primary safety outcome was symptomatic intracranial hemorrhage (sICH); secondary safety outcomes included any-ICH and 3-month all-cause mortality. Subgroup and network meta-analyses were performed evaluating the effects of different thrombolytic agents. RESULTS: = 0%) compared with BMT alone. Similar rates of 3-month good functional outcome, 3-month mortality, sICH and any-ICH were observed. Although no significant subgroup differences emerged, in the network meta-analysis alteplase ranked highest in efficacy surface under the cumulative rank curve (SUCRA): 90%, followed by tenecteplase (61%) and urokinase (40%) in achieving 3-month excellent functional outcome. CONCLUSIONS: IAT improves excellent functional outcomes without compromising safety in LVO-AIS patients with successful recanalization after EVT. TRIAL REGISTRATION: The prespecified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD420251035903).