Abstract
The cholesteryl ester transfer protein (CETP) plays an integral role in the metabolism of plasma lipoproteins. Despite two failures, CETP inhibitors are still in clinical development. We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport. We discuss the two failed CETP inhibitors, torcetrapib and dalcetrapib, and attempt to extract lessons learned. Two CETP inhibitors, anacetrapib and evacetrapib, are in phase III development, and we attempt to differentiate them from the failed drugs. Whether pharmacologic CETP inhibition will reduce the risk of cardiovascular disease is one of the most fascinating and important questions in the field of cardiovascular medicine.
MeSH terms
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Amides
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Anticholesteremic Agents / adverse effects
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Anticholesteremic Agents / therapeutic use*
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Atherosclerosis / genetics
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Atherosclerosis / prevention & control*
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Benzodiazepines / therapeutic use
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Cholesterol / metabolism*
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Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
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Cholesterol Ester Transfer Proteins / genetics
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Cholesterol, HDL / blood
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Cholesterol, LDL / blood
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Clinical Trials as Topic
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Coronary Disease / genetics
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Coronary Disease / prevention & control*
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Esters
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Humans
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Oxazolidinones / therapeutic use
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Quinolines / therapeutic use
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Sulfhydryl Compounds / therapeutic use
Substances
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Amides
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Anticholesteremic Agents
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Cholesterol Ester Transfer Proteins
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Cholesterol, HDL
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Cholesterol, LDL
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Esters
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Oxazolidinones
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Quinolines
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Sulfhydryl Compounds
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Benzodiazepines
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dalcetrapib
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torcetrapib
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evacetrapib
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Cholesterol
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anacetrapib