Effects of Intensive LDL-C Lowering with PCSK9 Inhibitors on Plaque Regression and Stabilization Assessed by Serial Intravascular Ultrasound and Optical Coherence Tomography in Patients with Acute Coronary Syndrome and Residual Inflammatory Risk

Patients with acute coronary syndrome (ACS) remain at substantial risk for recurrent ischemic events despite contemporary guideline-directed medical therapy, particularly when residual inflammatory and lipid-related risk persists. Intensive low-density lipoprotein cholesterol (LDL-C) reduction with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has demonstrated significant reductions in major adverse cardiovascular events. However, the mechanistic effects of PCSK9 inhibition on coronary plaque morphology, regression, and stabilization at the microstructural level remain incompletely characterized. Serial intracoronary imaging techniques, including intravascular ultrasound (IVUS) and optical coherence tomography (OCT), provide complementary insights into plaque burden, lipid content, fibrous cap thickness, and features associated with plaque vulnerability. Integration of these imaging modalities enables comprehensive longitudinal evaluation of atherosclerotic plaque evolution following aggressive lipid-lowering therapy. This study aims to investigate the impact of intensive LDL-C reduction with PCSK9 inhibitors on coronary plaque regression and stabilization in patients with ACS and persistent inflammatory activity. The project will evaluate changes in plaque volume, lipid core burden, fibrous cap thickness, macrophage infiltration, and other vulnerability markers using serial IVUS and OCT assessments. Additionally, the study will explore the relationship between imaging-derived plaque modifications, circulating inflammatory biomarkers, and subsequent clinical outcomes. By integrating multimodality intracoronary imaging with advanced lipid-lowering strategies, this work seeks to enhance understanding of plaque biology and provide mechanistic evidence supporting personalized therapeutic approaches for secondary prevention in high-risk ACS populations.