Time-independent value of IV thrombolysis in stroke thrombectomy: Evidence from a multicenter cohort

While endovascular thrombectomy (EVT) has revolutionized acute ischemic stroke (AIS) treatment, the benefit of pre-treatment with intravenous thrombolysis (IVT) remains uncertain. This study aimed to evaluate whether IVT was associated with improved EVT outcomes when patients undergo EVT within or beyond the 4.5-hour window.

We retrospectively analyzed AIS patients with anterior circulation large vessel occlusion (LVO) treated at 46 international stroke centers from 2016 to 2025. Adults included were categorized as early-thrombectomy (EVT performed within 4.5 h of onset) or late-thrombectomy (EVT performed after 4.5 h of onset) based on the time from onset to presentation to thrombectomy center. Patients were further bifurcated by IVT status. Outcomes included functional independence (90-day mRS 0-2), successful recanalization, embolization to new territory, and symptomatic intracranial hemorrhage (sICH). Multiple logistic regression, interaction testing and propensity score matching were performed.

Among 7118 patients who met inclusion criteria, IVT use independently predicted favorable outcome in all cohorts (adjusted OR [aOR] 1.40; p < 0.001). Late-thrombectomy presentation was a negative predictor (aOR 0.56; p < 0.001). No significant interaction was found between IVT and thrombectomy treatment window for functional outcome, recanalization, distal embolization, or sICH. Stratified analyses showed bridging therapy was associated with higher odds of functional independence in both early (aOR 1.56, p < 0.001) and late (aOR 1.27, p = 0.01) thromectomy groups, without increased sICH. In the matched bridging cohort (n = 1022), early-thrombectomy patients had greater functional independence (OR 1.65, p = <0.001) but no difference in sICH or distal embolization compared with late-thrombectomy patients (p > 0,05).

In this large real-world EVT cohort, IVT before thrombectomy was associated with improved functional outcomes without measurable safety penalties irrespective of whether patients underwent early or late EVT. The favorable association was stronger among early presenters but remained significant in the late thrombectomy group, providing real-world data for stroke systems of care built around inter-hospital transfer.