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Lipid-Lowering Agents.

Robert A Hegele1, Sotirios Tsimikas2

  • 1From the Department of Medicine and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada (R.A.H.).

Circulation Research
|February 1, 2019
PubMed
Summary

Genetic insights are driving the development of new dyslipidemia drugs. These emerging therapies target low-density lipoprotein cholesterol, triglycerides, and lipoprotein(a), with some aiming to increase high-density lipoprotein cholesterol.

Keywords:
atherosclerosisdyslipidemiashumanslipoprotein(a)oligonucleotides, antisense

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Area of Science:

  • Pharmacology
  • Genetics
  • Cardiovascular Medicine

Background:

  • Dyslipidemia treatments are increasingly informed by human genetic evidence.
  • Genetic studies, including family observations and Mendelian randomization, guide drug discovery.
  • Focus areas include reducing LDL cholesterol, triglycerides, and Lp(a), and increasing HDL cholesterol.

Purpose of the Study:

  • To review emerging drugs for dyslipidemia.
  • To highlight the role of genetic evidence in their development.
  • To categorize drugs based on their primary lipid target.

Main Methods:

  • Literature review of genetic evidence and drug development in dyslipidemia.
  • Categorization of drugs based on their molecular targets and effects on lipid profiles.
  • Identification of specific drug names and their primary lipid targets.

Main Results:

  • Several drugs primarily target LDL cholesterol: Lomitapide, mipomersen, AAV8.TBG.hLDLR, inclisiran, bempedoic acid, and gemcabene.
  • Alipogene tiparvovec, pradigastat, and volanesorsen primarily target elevated triglycerides.
  • Evinacumab and IONIS-ANGPTL3-LRx target both LDL cholesterol and triglycerides.
  • IONIS-APO(a)-LRx targets lipoprotein(a).

Conclusions:

  • Human genetic evidence is a significant driver for novel dyslipidemia drug development.
  • Emerging therapies offer targeted approaches to manage complex lipid disorders.
  • The pipeline includes agents for LDL cholesterol, triglycerides, Lp(a), and combinations thereof.