Abstract 22: Time to Treatment and the Effect of Intravenous Thrombolysis Before Thrombectomy: An Individual Participant Data Meta-Analysis

Abstract

Introduction: The benefit of intravenous thrombolysis for acute ischemic stroke declines with longer time from symptom onset. It is not known whether a similar time-dependent treatment effect modification of intravenous thrombolysis (IVT) is present in patients undergoing thrombectomy. Methods: Individual participant data meta-analysis from six randomized controlled trials comparing IVT plus thrombectomy vs thrombectomy alone. Primary analysis was performed testing for heterogeneity of the treatment effect. We estimated the effect of onset-to-expected-IVT times on the association between allocated treatment (intravenous thrombolysis plus thrombectomy vs thrombectomy alone) and disability at 3 months (modified Rankin scale, mRS). Results: In 2313 participants (IVT plus thrombectomy [n = 1160]; thrombectomy alone [n = 1153]; median age, 71 years, IQR 62-78 years; 44.3% female), the median onset-to-expected-IVT time was 2h 28min (IQR, 1h 46min to 3h 17min). We observed a statistically significant interaction between onset-to-expected-IVT times and treatment group effect (pinteraction=0.02), with the treatment effect of IVT plus thrombectomy vs thrombectomy alone declining over time (e.g., common adjusted Odds Ratio for a one-step mRS shift toward improvement 1.49, 95%CI 1.13-1.96 at 1h; 1.25, 95% CI 1.04-1.49 at 2h; 1.04, 95% CI 0.88-1.23 at 3h). If treated before 2h 20min after symptom onset, participants allocated to IVT plus thrombectomy were significantly less disabled at 90 days than participants allocated to thrombectomy alone. Conclusions: This individual participant data meta-analysis of patients with ischemic stroke presenting at thrombectomy-capable stroke centers demonstrated time-dependence of the treatment effect of IVT plus thrombectomy vs thrombectomy alone. Intravenous thrombolysis showed clinical benefit if it was administered within 2h 20min after symptom onset.