Time-Dependent Efficacy of Thrombolysis Before Thrombectomy: Registry of Stroke Care Quality (RES-Q).

Abstract

<b>Background:</b> Randomized evidence suggests that the association of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) may be time-dependent. We evaluated whether treatment timing modifies the association of IVT+EVT versus EVT alone with short-term in-hospital outcomes. <b>Methods:</b> We conducted a multinational observational registry cohort study using RES-Q data (2022-2024) from 38 countries. Among 3,132 eligible anterior-circulation large-vessel occlusion patients treated with EVT, 3,009 comprised the analytic cohort (IVT+EVT or EVT alone). Primary outcome was ordinal modified Rankin Scale (mRS) at discharge; secondary outcomes were mRS 0-2 at discharge and in-hospital survival. Time strata were ≤100, >100-150, >150-255, and >255 minutes. Confounding was addressed with stabilized inverse probability of treatment weighting (IPTW; weights truncated at 10) using a propensity score including arrival mode, admission location/department, vascular risk factors (hypertension, diabetes, hyperlipidemia, atrial fibrillation, prior stroke, smoking), imaging type, and baseline NIHSS. For EVT-only patients, onset-to-needle time was predicted only to assign time strata. <b>Results:</b> The mean age was 69.2 years (SD 13.2) and 45.6% were female. Treatment-by-time interaction was significant for ordinal discharge mRS (p=0.002) and mRS 0-2 at discharge (p=0.02). IVT+EVT was associated with better outcomes in the earliest treatment windows: at ≤100 minutes, ordinal mRS odds ratio (OR) 1.99 (95% CI, 1.49-2.63), in-hospital survival OR 1.81 (1.13-2.92), and mRS 0-2 OR 1.76 (1.24-2.51); at >100-150 minutes, ordinal mRS OR 1.58 (1.21-2.06) and mRS 0-2 OR 1.64 (1.16-2.31). Associations were attenuated beyond 150 minutes. <b>Conclusions:</b> In routine practice, early IVT before EVT was most consistently associated with improved discharge outcomes.