Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors With Statin for ACS Patients

Cardiovascular diseases (CVDs) remain the leading cause of death globally, with a dominant contribution from atherosclerotic CVD (ASCVD).

• Percutaneous coronary intervention (PCI) is a key method for revascularization in ASCVD patients, improving their prognosis. With the continuous advancement of PCI in recent years, its indications have become increasingly diverse. However, patients still face a pronounced residual risk post-PCI. Research indicates that plaque vulnerability and other risk factors contribute to a 15%-20% rate of major adverse cardiovascular events (MACE) within one year following PCI.
• The pathological mechanism of atherosclerosis is closely tied to the abnormal deposition of low-density lipoprotein cholesterol (LDL-C) beneath the vascular endothelium. This lipid particle can provoke a chronic inflammatory response in the vessel wall, eventually causing plaque formation. Moreover, the marked elevation of LDL-C levels is highly connected to the occurrence and progression of ASCVD.
• Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease worldwide, with a prevalence of approximately 25% (range 14%-32%).
• It is regarded as the hepatic manifestation of metabolic syndrome (MetS) and is strongly associated with obesity and diabetes mellitus (DM).
• Cardiovascular (CV) disease is one of the leading causes of death in patients with MASLD
• Statins are the cornerstone of lipid-lowering therapy, noticeably diminishing LDL-C levels by blockading HMG-CoA reductase. For patients following PCI, several guidelines suggest high-intensity statin therapy to reach a target LDL-C level of ≤1.4 mmol/L and a ≥50% decline from baseline.
• However, even with intensive statin therapy, many post-PCI patients still exhibit LDL-C levels above the target limits.
• Inhibitors of proprotein convertase subtilisin/kexin type 9(PCSK9) notably decrease plasma LDL-C levels by preventing the binding of PCSK9 protein to LDL-C receptors (LDLR) on hepatocyte surfaces, thereby decreasing LDLR degradation. In 2019, guidelines for managing dyslipidemia from the ESC/EAS emphasize that PCSK9 inhibitors should be added for patients with insufficiently controlled LDL-C levels to achieve the target levels.
• Combining PCSK9 inhibitors with statins has been proven to lead to a 60%-70% reduction in LDL-C levels.
• Recently, a novel non-invasive parameter to assess steatosis has been developed using the Fibroscan® which is a vibration-controlled transient elastography (VCTE™) device used to assess liver elasticity which is related to liver fibrosis. This novel physical parameter, based on the properties of ultrasonic signals acquired by the Fibroscan®, is called the controlled attenuation parameter (CAP). It uses the postulate that fat affects ultrasound propagation, and is a measure of ultrasound attenuation at the central frequency of the Fibroscan
• In this study, the investigators will demonstrate overall effect of PCSK9 inhibitors in combination with statins on MASLD and lipid levels for post-PCI patients, and to compare the degree of risk reduction with statin monotherapy.