Tag : LOW-DENSITY LIPOPROTEIN CHOLESTEROL

The Ez-PAVE trial showed that intensive LDL-C targeting <55mg/dL significantly reduced 3-year composite cardiovascular events compared with conventional targeting <70mg/dL in patients with ASCVD, without increasing major safety concerns, supporting a more aggressive LDL-C control in line with current guidelines.

A prespecified subgroup analysis from the VESALIUS-CV trial showed that evolocumab significantly reduced first major adverse cardiovascular events (MACE) in high-risk patients with diabetes without established atherosclerosis. Over 5 years, evolocumab lowered median low-density lipoprotein cholesterol (LDL-C) to 44mg/dL and reduced 3-point MACE, cardiovascular death, and all-cause mortality, supporting earlier lipid-lowering intensification.

Lerodalcibep is a third-generation proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor that prevents PCSK9 from binding to low-density lipoprotein receptors (LDLRs). Low-density lipoprotein-cholesterol (LDL-C) clearance from the bloodstream is enhanced as a result of LDLR degradation being blocked. Compared to monoclonal antibodies (mAbs), lerodalcibep is smaller in size and has a higher solubility, enabling prolonged and stable LDL-C reductions. In a prior phase 2 trial, lerodalcibep at a dose of 300mg monthly was shown to be effective in lowering LDL-C by >70%.

Bempedoic acid inhibits ATP citrate lyase, an enzyme upstream of 3-hydroxy-3-methalglutaryl-coenzyme (HMG-CoA) reductase which is the rate-limiting step of cholesterol biosynthesis. This reduces hepatic cholesterol synthesis and raises LDL receptor expression, increasing the clearance of LDL-C from the circulation.