Pharmacogenetics of Lipid-Lowering Agents: an Update Review on Genotype-Dependent Effects of HDL-Targetingand Statin Therapies

Curr Atheroscler Rep. 2017 Sep 25;19(11):43. doi: 10.1007/s11883-017-0679-5.

Abstract

Purpose of review: High-density lipoproteins (HDL) are involved in reverse cholesterol transport. Results from randomized trials of HDL-targeting therapies, including cholesteryl ester transfer protein (CETP) inhibitors, have shown a lack of benefit in unsegmented populations. These observations could be explained by inter-individual variability of clinical responses to such agents depending on the patients' genotypes. In parallel, although lowering of LDL cholesterol (LDL-c) with statin therapy reduces the risk of vascular events in a wide range of individuals, inter-individual variability exists with regard to LDL-c-lowering response as well as efficacy in reducing major cardiovascular events.

Recent findings: Pharmacogenomic analyses were performed in the dal-OUTCOMES and dal-PLAQUE-2 studies. Beneficial and concordant results were observed in patients with the favorable genotype when treated with the CETP inhibitor dalcetrapib. Similarly, previous studies revealed genetic variants associated with differential LDL-c response to statin therapy. In this review, we discuss the pharmacogenetic determinants of HDL-targeting and statin therapy responses in light of the latest available published data, and their potential therapeutic applications.

Keywords: Cardiovascular disease; Cholesteryl ester transfer protein (CETP) inhibitors; High-density lipoproteins (HDL); Pharmacogenetics; Statins.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents / therapeutic use
  • Cholesterol, HDL / genetics
  • Cholesterol, HDL / metabolism
  • Clinical Trials as Topic
  • Genotype
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypolipidemic Agents / therapeutic use*
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • Pharmacogenetics

Substances

  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipoproteins, HDL