Impact of enlarged perivascular spaces on endovascular therapy outcomes in patients with large ischaemic core: A post-hoc analysis of the ANGEL-ASPECT trial.

Background and objectives: Enlarged perivascular spaces (EPVSs), particularly in the basal ganglia (BG), are indicators of microvascular dysfunction and impaired glymphatic clearance, which may influence stroke outcomes. Determining the threshold below which endovascular therapy (EVT) confers no additional benefit is clinically important for patients with large ischaemic infarcts.

Methods: This post-hoc analysis utilized data from the ANGEL-ASPECT trial (NCT04551664), a multicentre, randomized controlled trial of 456 acute ischaemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) and a large ischaemic core. Among these patients, 226 who with completed, high-quality brain magnetic resonance imaging (MRI) were included. BG-EPVS severity was assessed on T2-weighted MRI and categorized as none-to-mild, moderate, or severe. The primary outcome was the 90-day modified Rankin scale (mRS) score.

Results: EVT significantly improved 90-day mRS outcome in patients with none-to-mild (adjusted common odds ratio [cOR] 5.50, 95% CI: 2.72-11.16, P < 0.001) and moderate (adjusted cOR 4.03, 95% CI, 1.46-11.15, P = 0.007) BG-EPVS. However, the benefit was markedly attenuated and not statistically significant in patients with severe BG-EPVS (adjusted cOR, 1.07 95% CI, 0.25-4.67, P = 0.926). EVT also increased the likelihood of achieving favourable functional outcomes (mRS scores of 0-2 and 0-3) and early neurological improvement (ENI) in the none-to-mild BG-EPVS subgroup, and favourable outcome (mRS score of 0-2) in the moderate BG-EPVS subgroup, but not in the severe BG-EPVS subgroup. Significant treatment-by-BG-EPVS interactions were observed for achieving an mRS score of 0-3 (P_interaction = 0.005) and ENI (P_interaction = 0.029).

Conclusions: EVT was associated with significantly improved 90-day functional outcomes in LVO-AIS patients with a large ischaemic core and none-to-mild or moderate BG-EPVS, whereas this benefit was not observed in those with severe BG-EPVS. Given the limited power in subgroup analyses, these findings should be considered hypothesis-generating and warrant validation in larger, adequately powered randomized controlled trials.