Significance of occlusion site on outcomes in stroke patients with large infarction undergoing endovascular therapy: A prespecified subgroup analysis of the ANGEL-ASPECT trial

Background: Randomized studies have demonstrated the efficacy of endovascular therapy (EVT) for acute large vessel occlusion with large infarction. However, the impact of the occlusion site on EVT outcomes remains underexplored. Methods: We conducted this prespecified subgroup analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core (ANGEL-ASPECT) trial. Participants were enrolled within 24 h of symptom onset and had an Alberta Stroke Program Early Computed Tomography Score of 3 to 5 or an infarct core volume of 70–100 mL and were randomly assigned to undergo EVT or standard medical management (MM). All 455 patients were included and categorized into 2 subgroups by whether there was an internal carotid artery occlusion (ICAO) or middle cerebral artery occlusion (MCAO). The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We further assessed the association between onset-to-puncture time (OPT) and outcome in both groups using ordinal logistic regression and tested for an interaction between occlusion site and the effect of EVT. Results: A total of 164 patients (36.0%) had ICAO, while 291 patients (64.0%) had MCAO. The baseline characteristics of patients treated with EVT and MM were comparable in either the ICAO or MCAO groups. EVT benefit was observed in both groups without significant heterogeneity (p for interaction = 0.891). A significant statistic interaction between occlusion site and treatment on any intracranial hemorrhage (ICH) within 48 h was observed (p for interaction = 0.002), with ICAO significantly increasing the risk of ICH compared to MCAO in patients undergoing EVT (ICAO: common OR, 6.34; 95% CI, 2.84–14.16; MCAO: common OR, 2.19; 95% CI, 1.56–3.09). However, the risk of symptomatic ICH was not increased significantly in both groups. For patients with ICAO, when OPT exceeds about 10 h and 10 min, the benefit of EVT compared to MM is not significant. Conclusions: Although both ICAO and MCAO patients with large infarction could benefit from EVT, EVT increased the risk of any ICH in ICAO patients without increasing the risk of sICH. Longer OPT was associated with poorer EVT efficacy in patients with ICAO. Data access statement: The data supporting the findings of this study are available from the corresponding author upon reasonable request. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04551664.