Defective mitophagy in human Niemann-Pick Type C1 neurons is due to abnormal autophagy activation.

BACKGROUND AND PURPOSE: The combination of PCSK9 inhibitors and moderate statin therapy effectively stabilizes intracranial atherosclerotic plaques in patients with intracranial atherosclerotic stenosis (ICAS). This study aimed to explore the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on plaque characteristics in patients with symptomatic ICAS (sICAS) in the anterior circulation over a 6-month follow-up.

METHODS

This study is a single-center, prospective, observational study, which continuously included stroke patients with sICAS in the anterior circulation. The patients were divided into two groups: the standard treatment group (atorvastatin) or the intensive treatment group (evolocumab combined with atorvastatin). The primary outcome is the change of atherosclerotic plaque characteristics over 6 months.

RESULTS

A total of 50 patients were enrolled in this study, with 34 patients ultimately included in the analysis (15 in the standard treatment group and 19 in the intensive treatment group). Both groups succeeded in reducing low-density lipoprotein-cholesterol (LDL-C) levels, and the intensive treatment group showed a more pronounced reduction (P < 0.001). The intensive treatment group exhibited a significant improvement in the degree of stenosis (P = 0.001). Notable disparities were observed between the standard treatment group and the intensive treatment group regarding percentage change of plaque length (-85.70 vs. -1.25%, P = 0.009) and plaque volume after 6 months (265.06 vs. 125.34 mm3, P = 0.018).

CONCLUSION

Compared with statins alone, the utilization of PCSK9 inhibitors demonstrated a marked improvement in the progression of arteriosclerosis, effectively reducing stenosis degree, plaque length, and volume.