Cardiovascular Therapeutics at the Crossroads: Pharmacological, Genetic, and Digital Frontiers

Figure 1. Mechanisms of novel lipid-lowering therapies: PCSK9 inhibitors, inclisiran, and bempedoic acid. The figure illustrates the distinct molecular mechanisms of three next-generation lipid-lowering agents. PCSK9 inhibitors prevent PCSK9 from binding to LDL receptors (LDL-R), allowing receptor recycling and enhanced LDL clearance. Inclisiran, a small interfering RNA conjugated with GalNAc, targets PCSK9 mRNA in hepatocytes, reducing its synthesis. Bempedoic acid inhibits ATP-citrate lyase, decreasing cholesterol biosynthesis and upregulating LDL receptor expression. Together, these agents improve lipid control and reduce cardiovascular risk. Abbreviations: PCSK9, proprotein convertase subtilisin/kexin type 9; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; ASGPR, Asialoglycoprotein receptor; RISC, RNA-induced silencing complex; ACLY, adenosine triphosphate-citrate lyase; CoA, Coenzyme A; mRNA, messenger RNA; LEC, liver endothelial cell.

Figure 2. Comparative overview of cardiometabolic drug classes: SGLT-2 inhibitors, GLP-1 receptor agonists, and dual GIP/GLP-1 receptor agonists. The figure summarizes the principal mechanisms and class-wide clinical effects of three major therapeutic groups contributing to cardio-renal-metabolic protection. Abbreviations: SGLT-2i, sodium-glucose co-transporter type 2 inhibitors; GLP-1, glucagon-like peptide-1; RA, receptor agonist, GIP, glucose-dependent insulinotropic polypeptide; CKD, chronic kidney disease; MACEs, major adverse cardiovascular events.