Effects of different statin-based lipid-lowering therapies on stabilization and regression of carotid plaque: a randomized open-label trial

Abstract

Background Atherosclerotic plaques in the carotid arteries are significant risk factors for cardiovascular events. This study aimed to evaluate the efficacy of different statin-based lipid-lowering therapies, including statins and the addition of ezetimibe or PCSK9 inhibitors, in stabilizing and regressing carotid plaques in a high cardiovascular risk population. Methods In this randomized open-label trial, participants were randomly assigned to one of four treatment groups: atorvastatin 20 mg/day (Statin), atorvastatin 10 mg/day + ezetimibe 10 mg/day (Statin_E), atorvastatin 10 mg/day + alirocumab 75 mg every 2 weeks (Statin_P), and atorvastatin 10 mg/day + ezetimibe 10 mg/day + alirocumab 75 mg every 2 weeks (Statin_EP). The primary outcomes were carotid plaque regression or progression at 12 months. Secondary outcomes included plaque morphological stabilization assessed by contrast-enhanced ultrasound (CEUS) and changes in blood lipid levels after 6 months. Results At 6 months, the Statin_P and Statin_EP groups exhibited significantly lower LDL-C levels compared to the Statin and Statin_E groups (p < 0.05). The proportion of intraplaque neovascularization (IPN) scales were significantly different (p = 0.02, CI 95% [0.00, 0.12]) between the groups after treatment, and the IPN was prominently reduced in the Statin_P and Statin_EP groups. At 12 months, Statin_P and Statin_EP groups showed the greatest reduction in carotid plaque size, with significant differences in plaque regression across all treatment groups (p < 0.05, p = 2.65e−08, CI 95% [0.04, 1.00]). The highest proportions of plaque regression were observed in the Statin_P and Statin_EP groups (p < 0.05, p = 1.76e−07, CI 95% [0.09, 0.22]). Conclusion The combination of moderate-dose statins with PCSK9 inhibitors is significantly more effective than statin monotherapy or statin-ezetimibe combinations in stabilizing and regressing atherosclerotic carotid plaques. These findings suggest that statin-based combination lipid-lowering therapies offer substantial potential for reducing cardiovascular risk in high-risk Asian populations. Trial Registration The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2200058389) on 2022-04-08.