Effects of Different Intensive Lipid-Lowering Therapies on Stabilization and Regression of Carotid Plaque: A Randomized Open-Label Trial

Abstract

Background Atherosclerotic plaques in carotid arteries are significant predictors of cardiovascular events such as stroke and myocardial infarction. Lipid-lowering therapies, particularly statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have shown promising in plaque regression and stabilization, which are crucial for cardiovascular disease (CVD). Methods This randomized open-label trial was conducted at the Third Affiliated Hospital of Guangzhou Medical University from March 2022 to December 2023. The study included patients at high CVD risk with non-calcified carotid plaque. Participants were randomized into four groups: statin alone (Statin), statin plus ezetimibe (Statin_E), statin plus alirocumab (Statin_P), and statin plus ezetimibe and alirocumab (Statin_EP). The primary outcomes were morphological stabilization of carotid plaque at 6 months and regression at 12 months, assessed by contrast-enhanced carotid ultrasonography. Secondary outcomes were changes in blood lipid levels. Results A total of 312 high CVD risk patients were enrolled, among whom 299 completed the study. After six months, patients in the Statin_P and Statin_EP groups showed significantly lower levels of total cholesterol and low-density lipoprotein cholesterol compared to the other groups. These patients also demonstrated a significantly greater proportion of plaques transforming from types I or II to types III or IV and a significant decrease in intraplaque neovascularization (P < 0.05), indicating the plaques in these groups had stabilized. After 12 months, the regression in plaque size was more pronounced in the Statin_P and Statin_EP groups (left: χ² = 26.37, p = 1.90e − 04, CI 95% [0.06, 1.00]; right: χ² = 19.00, p = 4.16e − 03, CI 95% [0.00, 1.00]). Conclusion Intensive lipid-lowering therapies that combine statins with PCSK9 inhibitors, such as alirocumab, are more effective in regressing carotid plaques and stabilizing plaque morphology compared to other treatments. These findings support the use of PCSK9 inhibitors in combination with statin therapy for managing atherosclerotic disease and reducing cardiovascular events. Trial registration: The trial was registered in the Chinese Clinical Trial Registry (Registration No. ChiCTR2200058389).