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The combination of a statin and a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitor is a potent lipid-lowering regimen used to achieve intensive reduction of LDL-cholesterol. Statins function by inhibiting HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis, which leads to an upregulation of LDL receptors. PCSK9 inhibitors, such as the monoclonal antibody evolocumab (Repatha), prevent the PCSK9-mediated degradation of these LDL receptors, thereby increasing their density on the hepatocyte surface and enhancing the clearance of circulating LDL particles. In the context of clinical trial NCT03962686, sponsored by the University of Campania Luigi Vanvitelli, this combination is being evaluated for its effects on carotid plaque composition, inflammatory markers, and methylase activity in patients with type 2 diabetes and carotid artery atherosclerosis.
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