Endovascular thrombectomy with or without intravenous alteplase in acute stroke: a systematic review and meta-analysis of randomized clinical trials

Background and purpose This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke within 4.5 h after onset. Methods PubMed and Embase were searched for eligible randomized controlled trials. The primary outcome was the rates of neurological functional independence defined as modified Rankin scale score 0-2 at 90 days, whose non-inferiority margin was set at - 15%, - 10%, - 6.5%, - 5%, and - 1.3% for its risk difference (RD). Results We included six studies enrolling 2334 participants. The crude cumulative rates of functional independence were 49.0% with direct EVT vs 50.9% with bridging therapy, without significant difference (Odd ratio [OR] = 0.93, 95% confidence interval [CI] 0.79-1.09) between two groups, where the pooled RD was - 2% (95% CI - 6 to 2%) whose lower 95% CI bound fell within non-inferiority margins of - 15%, - 10%, -6.5%, but not - 5% and - 1.3%. Between the two groups, no significant difference was found in excellent function rate (30.2% vs 30.6%, OR = 0.99, 95% CI 0.82-1.18) with RD of 0% (95% CI - 3 to 4%), mortality rate (16.0% vs 15.0%, OR = 1.08, 95% CI 0.86-1.35) with RD of 1% (95% CI - 2 to 4%), and symptomatic intracranial hemorrhage rate (4.3% vs 5.0%, OR = 0.86, 95% CI 0.58-1.27) with RD of 0% (95% CI - 2 to 1%). Conclusions No statistical difference was found in functional and safety outcomes between direct EVT and bridging therapy groups in acute stroke within 4.5 h after symptom onset. EVT alone was non-inferior to bridging therapy for several, but not the more stringent, non-inferiority margins.