Can we revive CETP-inhibitors for the prevention of cardiovascular disease?

Curr Opin Lipidol. 2022 Dec 1;33(6):319-325. doi: 10.1097/MOL.0000000000000854. Epub 2022 Oct 21.

Abstract

Purpose of review: To review recent developments in the field of cholesteryl ester transfer protein (CETP) inhibition from clinical trials and genomic analyses which have the potential to impact future clinical programs.

Recent findings: CETP plays an important role in remodelling of lipoproteins. A large body of evidence suggests that the presence of low CETP activity should have favourable effects on lipid profiles and cardiovascular risk. However, a number of clinical development programs of pharmacological CETP inhibitors have been disappointing with reports of toxicity and clinical futility. These findings have led many to consider abandoning CETP inhibition as a potential strategy for cardiovascular prevention. However, recent observations from genomic analyses and post hoc observations of prior clinical trials have given greater insights into the potential relationship between CETP inhibition and cardiovascular risk. This has highlighted the importance of lowering levels of atherogenic lipoproteins.

Summary: These findings provide a pathway for ongoing clinical development of CETP inhibitors, where the potential to play an important role in the prevention of cardiovascular disease may still be possible. The lessons learned and pathway forward for new CETP inhibitors will be reviewed.

Publication types

  • Review

MeSH terms

  • Anticholesteremic Agents* / therapeutic use
  • Atherosclerosis* / genetics
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / genetics
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol Ester Transfer Proteins
  • Humans
  • Lipoproteins / metabolism

Substances

  • Cholesterol Ester Transfer Proteins
  • Anticholesteremic Agents
  • Lipoproteins
  • CETP protein, human