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Can we revive CETP-inhibitors for the prevention of cardiovascular disease?
Stephen J Nicholls1, Kausik K Ray2, Adam J Nelson1
1Victorian Heart Institute, Monash University, Melbourne, Australia.
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.
Insights
Cholesteryl ester transfer protein (CETP) inhibition shows promise for cardiovascular disease prevention. Recent genomic and clinical trial analyses highlight the importance of lowering atherogenic lipoproteins for future therapeutic strategies.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Genetics
Background:
- Cholesteryl ester transfer protein (CETP) is crucial for lipoprotein remodeling.
- Low CETP activity is theoretically linked to improved lipid profiles and reduced cardiovascular risk.
- Previous CETP inhibitor trials faced challenges due to toxicity and lack of efficacy.
Conclusions:
- Recent findings provide a viable path for continued clinical development of CETP inhibitors.
- Lessons learned are crucial for designing next-generation CETP inhibitors.
- CETP inhibition may still play a significant role in preventing cardiovascular disease.
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