Pharmacogenomics of lipid-lowering agents: the impact on efficacy and safety

Per Med. 2023 Jan;20(1):65-86. doi: 10.2217/pme-2022-0041. Epub 2022 Nov 23.

Abstract

Hyperlipidemia is a significant risk factor for cardiovascular disease morbidity and mortality. The lipid-lowering drugs are considered the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Unfortunately, the lack of efficacy and associated adverse effects, ranging from mild-to-moderate to potentially life-threatening, lead to therapy discontinuation. Numerous reports support the role of gene polymorphisms in drugs' pharmacokinetic parameters and their associated adverse reactions. Therefore, this study aims to understand the pharmacogenomics of lipid-lowering drugs and the impact of genetic variants of key genes on the drugs' efficacy and toxicity. Indeed, genetically guided lipid-lowering therapy enhances overall safety, improves drug adherence and achieves long-term therapy.

Keywords: PCSK9; ezetimibe; fibrates; hyperlipidemia; statins; variants.

Plain language summary

Lipid-lowering drugs treat elevated lipid levels in the blood and reduce the risk of cardiovascular diseases and death. There are differences in the genetic makeup of people, which explains why different people may respond differently to lipid-lowering drugs. These genetic differences affect how the body absorbs, transports, metabolizes or eliminates lipid-lowering drugs. Some other genes may also control how much the body can absorb cholesterol and how much it can synthesize or metabolize it. As a result, people's risk of cardiovascular diseases varies due to differences in their genetic composition and how their bodies handle lipid-lowering drugs. Therefore, understanding the pharmacogenomics of lipid-lowering agents improves efficacy, enhances overall safety and achieves long-term therapy.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / genetics
  • Cholesterol, LDL / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypolipidemic Agents / therapeutic use
  • Pharmacogenetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol, LDL
  • Hypolipidemic Agents