Utility of Intravenous Alteplase Prior to Endovascular Stroke Treatment: A Systematic Review and Meta-analysis of RCTs

Objective: To provide a critical appraisal on the evidence from randomized-controlled clinical trials (RCTs) on the utility of direct endovascular treatment (dEVT) compared to the combination of endovascular treatment preceded by intravenous thrombolysis (bridging therapy, BT) for patients with acute large vessel occlusion (LVO). Methods: Eligible RCTs were identified by searching Medline and Scopus. We calculated the corresponding odds ratios (ORs) and 95% confidence intervals (95%CI) and pooled estimates using random-effects models. The primary outcome was the probability of modified Rankin scale (mRS) score of 0-2 at 3 months. Results: We included 3 studies comprising 1092 patients. No difference between dEVT and BT groups was detected for the outcomes of mRS 0-2 (OR=1.08,95%CI:0.85-1.38; adjusted OR=1.11, 95%CI:0.76-1.63), mRS 0-1 (OR=1.10, 95%CI:0.84-1.43; adjusted OR=1.16, 95%CI:0.84-1.61) and functional improvement at 3 months (common OR=1.08, 95%CI:0.88-1.34; adjusted common OR=1.09, 95%CI:0.86-1.37). Patients receiving dEVT had significantly lower likelihood of successful recanalization prior to the endovascular procedure compared to BT (OR=0.37, 95%CI:0.18-0.77). Patients receiving dEVT had lower intracranial bleeding rates compared to those receiving BT (OR=0.67, 95%CI:0.49-0.92), however, without significant difference in the probability of symptomatic intracranial hemorrhage. No differences in all-cause mortality, serious adverse events or procedural complications between the two groups were uncovered. Conclusions: We detected no differences in functional outcomes of IV thrombolysis eligible patients with an acute LVO receiving dEVT compared to BT. Since uncertainty for most endpoints remains large and the available data is not able to exclude the possibility of overall benefit or harm, further RCTs are needed.