Abstract Body: Background and Purpose: We aimed to investigate the effects of evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor for intensive lipid-lowering, on intracranial atherosclerotic stenosis (ICAS).
Methods: From a prospectively established high-resolution magnetic resonance imaging (HR-MRI) database, consecutive ICAS (>50%) patients with two detections of HR-MRI over six months were included in this study. The patients were divided into two groups: those with (evolucomab+) or without (evolocumab-) evolocumab add-on therapy. The primary outcomes were the percentage change in plaque burden and plaque response (plaque regression >5%) rate. The second outcome was the percentage change in stenosis degree. Cox regression analysis was used to estimate the association between evolocumab add-on therapy and the above outcomes in both general and subgroup (intensive statin vs. non-intensive statin) analysis.
Results: The data of 179 patients receiving statins and/or ezetimibe, 50 of which with evolucumab and 129 without, were analyzed. Evolocumab add-on therapy over six months showed a significant reduction in the percentage change of plaque burden (evolocumab+, median [IQR]: 0.08 [0.02-0.11] vs. evolocumab-: 0.02 [0.04-0.07]), increase in plague response rate (evolocumab+: 68.0% vs. evolocumab-: 34.1%), and reduction in the percentage change of stenosis degree (evolocumab+: 0.15 [0.01-0.34] vs. evolucumab-: 0.05 [-0.12-0.26]). After adjusting for potential confounders, evolocumab was significantly associated with the percentage reduction in plaque burden (estimate [95% CI], 0.074 [0.029-0.119]), the increase in plague response rate (6.70 [2.81-16.99]), and the percentage reduction in stenosis degree (0.198 [0.074-0.321]). In both intensive and non-intensive statin groups, evolocumab add-on therapy was still significantly associated with better outcomes in the percentage reduction in plague burden (intensive: 0.063 [0.004-0.121], P < 0.05; non-intensive: 0.126 [0.045-0.208], P < 0.01), the increase in plaque response rate (intensive: 3.75 [1.09-14.10], P < 0.05; non-intensive: 11.60 [2.55 – 52.82], P < 0.01), and the percentage reduction in stenosis degree (intensive: 0.148 [-0.015-0.312], P = 0.075; non-intensive: 0.331 [0.118-0.544], P < 0.01).
Conclusions: Evolocumab add-on therapy over six months is superior to statin alone in reversing symptomatic ICAS.