Background The efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT in such patients. We evaluated the efficacy and safety of EVT with or without IVT.

Methods The RESCUE-Japan LIMIT was an open-label, prospective, multicenter, randomized clinical trial to evaluate the efficacy and safety of EVT in stroke patients with large ischemic core, defined as Alberta Stroke Program Early CT Score (ASPECTS) 3–5. This subanalysis evaluated the differences in the effects of EVT with medical care (EVT group) compared with medical care alone (No-EVT group) between those who received IVT (IVT stratum) and those who did not (No-IVT stratum) before EVT.

Results Among 202 enrolled patients, 147 (73%) did not receive IVT. In the No-IVT stratum, the modified Rankin Scale (mRS) score of 0–3 at 90 days was significantly higher in the EVT group than in the No-EVT group (31.1% vs 12.3%, OR 3.21 (95% CI 1.37 to 7.53)). In the IVT stratum, the mRS score of 0–3 was 30.8% in the EVT group and 13.8% in the No-EVT group (OR 2.78 (95% CI 0.72 to 10.7)) (interaction p=0.77). The incidence of symptomatic intracranial hemorrhage was not different between the two groups in the No-IVT stratum (OR 1.20 (95% CI 0.35 to 4.12)), but it was significantly higher in the EVT group than in the No-EVT group in the IVT stratum (11.5% vs 0%, p=0.03).

Conclusions There was no difference in efficacy of EVT with or without IVT, while IVT before EVT might increase symptomatic intracranial hemorrhage in patients with large ischemic core.

Trial registration information NCT03702413.