Efficacy and safety of intra-arterial thrombolysis after endovascular reperfusion for acute ischemic stroke: a systematic review and meta-analysis of randomized trials

Objective: This pooled analysis aims to evaluate the efficacy and safety of intra-arterial thrombolysis (IAT) following near-complete to complete reperfusion by endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO). Methods: We conducted a search of PubMed, Embase, and Cochrane databases to identify randomized controlled trials (RCTs) investigating the adjunct benefit of IAT in patients with AIS-LVO who had achieved a score on the Thrombolysis In Cerebral Infarction (TICI) scale of 2b-3 after EVT. Efficacy outcomes encompassed excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days, and functional independence (mRS 0-2). Safety outcomes included symptomatic intracranial hemorrhage (sICH) and mortality at 90 days. A network meta-analysis (NMA) was performed to evaluate the effects of different types of intra-arterial thrombolytic agents on mRS 0-1. Results: A total of 7 RCTs were included in the analysis, involving 2,128 patients. Relative risks (RR) and 95% confidence intervals (CI) were pooled using a random-effects model. The pooled results indicated that adjunctive IAT did not significantly improve the rate of functional independence (RR 1.04, 95% CI 0.96-1.13, P = 0.29). However, there was a significant increase in excellent functional outcome with adjunctive IAT (RR 1.23, 95% CI 1.11-1.36, P < 0.001). The pooled analysis did not demonstrate any differences between EVT + IAT and EVT only in rates of sICH (RR 1.23, 95% CI 0.81-1.85, P = 0.33) or 90-day mortality (RR: 0.98, 95% CI: 0.82-1.18; P = 0.86). The NMA found no significant difference in achieving mRS 0-1 among arterial adjunctive alteplase, tenecteplase, and urokinase following successful reperfusion. Conclusions: IAT as an adjunct to successful EVT appears to enhance excellent functional outcome in patients with AIS-LVO without a significant increase in sICH and mortality.