Time-Dependent Efficacy of Thrombolysis Before Thrombectomy: RES-Q

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.

We conducted a multinational observational registry cohort study using RES-Q (Registry of Stroke Care Quality) data (2022-2024) from 38 countries. Among 3132 eligible anterior-circulation large-vessel occlusion patients treated with EVT, 3009 comprised the analytic cohort (IVT+EVT or EVT alone). The primary outcome was the ordinal modified Rankin Scale (mRS) score at discharge; secondary outcomes were the mRS score 0 to 2 at discharge and in-hospital survival. Time strata were ≤100, >100 to 150, >150 to 255, and >255 minutes. Confounding was addressed with stabilized inverse probability of treatment weighting (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 National Institutes of Health Stroke Scale score. For EVT-only patients, onset-to-needle time was predicted only to assign time strata.

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 score (P=0.002) and mRS score 0 to 2 at discharge (P=0.02). IVT+EVT was associated with better outcomes in the earliest treatment windows: at ≤100 minutes, ordinal mRS score odds ratio (OR) 1.99 (95% CI, 1.49-2.63), in-hospital survival OR, 1.81 (95% CI, 1.13-2.92), and mRS score 0 to 2 OR, 1.76 (95% CI, 1.24-2.51); at >100 to 150 minutes, ordinal mRS score OR, 1.58 (95% CI, 1.21-2.06) and mRS score 0 to 2 OR, 1.64 (95% CI, 1.16-2.31). Associations were attenuated beyond 150 minutes.

In routine practice, early IVT before EVT was most consistently associated with improved discharge outcomes.