Relation between Time from Onset to Randomization and Benefit Magnitude in Recent Clinical Trials of Thrombectomy for Patients with Large Ischemic Cores.

Abstract

Six randomized trials have demonstrated the benefit of endovascular thrombectomy (EVT) for patients with large ischemic core stroke, but the extent to which treatment effect diminishes with increasing onset-to-treatment time remains unclear. We evaluated whether trial-level median time from symptom onset to randomization modifies the absolute EVT effect compared with medical management (MM). Using study-level data from six trials (n=1,881), we modeled differences in 90-day utility-weighted modified Rankin Scale (uw-mRS) outcomes between EVT and MM as a function of median onset-to-randomization time via Bayesian regression, selecting models based on deviance information criteria. Increasing time was strongly associated with declining EVT benefit (posterior probability =0.9925). The absolute treatment effect fell below 0.10 at 10 hours (95% CrI, 7-15) and below 0.03 at 18 hours (95% CrI, 12-33). These findings suggest that treatment delays attenuate EVT benefit and may inform hypothesis generation and future trial design in acute stroke.