Assessing the impact of evolocumab on thin-cap fibroatheroma and endothelial function in patients with very high-risk atherosclerotic cardiovascular disease: a study protocol for a randomized controlled trial.

Background: The prevalence of very high-risk atherosclerotic cardiovascular disease (ASCVD) is significant in China, with suboptimal rates of low-density lipoprotein cholesterol (LDL-C) compliance exacerbating plaque instability and causing a higher incidence of major adverse cardiac events (MACEs). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are effective in reducing LDL-C levels, increase the stability of vulnerable plaque, and influence the progression of atherosclerosis through multiple mechanisms as demonstrated in animal studies. However, there is currently a lack of evidence regarding the efficacy and safety of high-intensity statin therapy combined with PCSK9i in the secondary prevention of ASCVD in the Chinese population. This study aims to demonstrate the efficacy of high-intensity statins combined with PCSK9i on vulnerable plaques in very high-risk ASCVD patients through intravascular imaging and non-invasive endothelial function test.

Methods: This randomized, open-label, prospective clinical study involves 240 patients with very high-risk ASCVD who meet the criteria outlined in the 2023 Chinese lipid management guidelines. Patients recruitment will be processed in Beijing Anzhen Hospital from January 2021 to December 2024. Patients with thin-cap fibroatheroma (TCFA) detected by optical coherence tomography (OCT) are randomly assigned in a 1:1 ratio to the evolocumab group (evolocumab 140 mg every 2 weeks plus atorvastatin 40 mg nightly) or the standard treatment group (atorvastatin 40 mg nightly). The primary endpoint is the absolute change of the minimum fibrous cap thickness (FCT) at a median follow-up of 1 year. The secondary endpoints are other OCT metrics, assessment of MACE rates, alterations in serum lipid profiles and markers of inflammation, endothelial function, and adverse drug reactions. Logistic regression, analysis of covariance (ANCOVA), Kaplan-Meier curve survival analysis, and Cox regression will be used to investigate the relationship between variables and endpoints.

Discussion: The purpose of this study is to evaluate the efficacy of high-intensity statin therapy combined to PCSK9i for the secondary prevention of coronary artery disease in Chinese patients with very high-risk ASCVD. The results will provide evidence to optimize the management of this high-risk population.

Trial Registration: This study was registered on chictr.org.cn (ChiCTR2000032570).