Pharmacogenomics of Lipid-Lowering Agents: the Impact on Efficacy and Safety

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.

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.

Keywords::

• ezetimibe
• fibrates
• hyperlipidemia
• PCSK9
• statins
• variants

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.