Threshold effect of post-stenting residual stenosis in severe intracranial stenosis: a post hoc analysis of a randomized clinical trial

Background: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke. Although intracranial stenting is used in select patients, optimal post - procedural residual stenosis remains unclear. This post hoc analysis aimed to assess the association between post-stenting residual stenosis and 1-year clinical and angiographic outcomes and to explore potential nonlinear and threshold effects. Methods: This post hoc analysis of the NOVA randomized clinical trial included 242 patients with symptomatic 70–99% ICAS who underwent intracranial stenting. Patients were categorized into tertiles according to residual stenosis (T1, n=81; T2, n=80; and T3, n=81). The primary endpoint was a composite of any stroke or death within 30 days or ischemic stroke in the target vessel territory from day 31 to 1 year. Restricted cubic spline (RCS) and piecewise regression analyses were used to explore nonlinear associations and threshold effects. Results: Among 195 patients with evaluable 1-year vascular imaging, in-stent restenosis (ISR) occurred in 9/65 (14%) in the T1 group, 10/65 (15%) in the T2 group, and 22/65 (34%) in the T3 group (P=0.01). A nonlinear relationship was observed between residual stenosis and the composite endpoint (P for overall =0.007; P for nonlinearity =0.03). A threshold effect was identified at 19.94% residual stenosis. Above this threshold, higher residual stenosis was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.105 per 1% increase; 95% confidence interval (CI) 1.037–1.178; P=0.002]. Early (≤30 days) stroke or death tended to be more frequent in the low residual stenosis group, whereas ischemic stroke between 31 days and 1 year occurred more often in patients with high residual stenosis. Conclusions: Residual stenosis after intracranial stenting showed a nonlinear association with the composite clinical outcome. A threshold was identified at approximately 20%, above which higher residual stenosis was associated with a greater risk of the composite endpoint. Further prospective studies are warranted to validate these findings. Trial Registration: ClinicalTrials.gov, NCT02578069.