Effects of PCSK9 Inhibitors on Other than Low-Density Lipoprotein Cholesterol Lipid Variables

J Cardiovasc Pharmacol Ther. 2018 Jan;23(1):3-12. doi: 10.1177/1074248417724868. Epub 2017 Aug 22.

Abstract

Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor, but other lipid variables such as triglycerides (TRGs), high-density lipoprotein cholesterol (HDL-C) and lipoprotein a [Lp(a)] also affect cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-C concentration but also modestly improve the concentrations of TRGs and HDL-C and more robustly decrease Lp(a) levels. The review presents the associated mechanisms of the beneficial effects of PCSK9 inhibitors on the other than LDL-C lipid variables, including the effects on lipid/apolipoprotein secretion and clearance and the heteroexchange between lipoproteins, as well as the possible effects on other variables involved in lipid metabolism such as sortilin. Proprotein convertase subtilisin/kexin type 9 inhibitors improve the overall lipid profile, and these beneficial effects may play a role in the reduction of cardiovascular risk.

Keywords: PCSK9 inhibitors; alirocumab; evolocumab; high-density lipoprotein; lipoprotein a; proprotein convertase subtilisin/kexin type 9; triglycerides.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood
  • Humans
  • Hypolipidemic Agents / pharmacology*
  • Lipid Metabolism / drug effects
  • Lipids / blood
  • PCSK9 Inhibitors*
  • Proprotein Convertase 9 / metabolism
  • Risk Factors

Substances

  • Cholesterol, LDL
  • Hypolipidemic Agents
  • Lipids
  • PCSK9 Inhibitors
  • PCSK9 protein, human
  • Proprotein Convertase 9