Can we revive CETP-inhibitors for the prevention of cardiovascular disease?. Issue 6 (21st December 2022)

• Record Type: Journal Article
• Authors: Nicholls, Stephen J.; Ray, Kausik K.; Nelson, Adam J.; Kastelein, John J.P.
• Is Part Of: Current opinion in lipidology. Volume 33:Issue 6(2022)
• Page Start: 319
• Page End: 325
• Publication Date: 2022-12-21
• Subjects: cholesteryl ester transfer protein -- clinical trials -- genetics -- lipids -- prevention; Lipids -- Periodicals; 572.574
• DOI: 10.1097/MOL.0000000000000854
• Languages: English
• ISSNs: 1473-6535

Abstract

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.