Evolving Therapeutic Targets: Cholesteryl Ester Transfer Protein Inhibition

Cholesteryl ester transfer protein (CETP) facilitates the exchange of esterified cholesterol from high-density lipoproteins (HDLs) to very-low-density lipoproteins and low-density lipoproteins (LDLs) in exchange for triglycerides. Population and genetic studies demonstrate an inverse association between CETP activity and cardiovascular risk. Preclinical studies have revealed that inhibiting CETP is atheroprotective. However, clinical trials have demonstrated no cardiovascular benefit with most CETP inhibitors and a modest benefit with anacetrapib. Insights from these studies provide the potential to continue development of CETP inhibitors as an approach to reducing cardiovascular risk.