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

Stephen J. Nicholls, Kausik K. Ray, Adam J. Nelson, John J. P. Kastelein

Research output: Contribution to journalReview articleAcademicpeer-review

5 Citations (Scopus)

Abstract

Purpose of reviewTo 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 findingsCETP 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.SummaryThese 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.
Original languageEnglish
Pages (from-to)319-325
Number of pages7
JournalCurrent opinion in lipidology
Volume33
Issue number6
DOIs
Publication statusPublished - 1 Dec 2022

Keywords

  • cholesteryl ester transfer protein
  • clinical trials
  • genetics
  • lipids
  • prevention

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