Abstract
The dramatic failure of clinical trials evaluating the cholesterol ester transfer protein inhibitor torcetrapib has led to considerable doubt about the value of raising high-density lipoprotein cholesterol (HDL-C) as a treatment for cardiovascular disease. These results have underscored the intricacy of HDL metabolism, with functional quality perhaps being a more important consideration than the circulating quantity of HDL. As a result, HDL-based therapeutics that maintain or enhance HDL functionality warrant closer investigation. In this article, we review the complexity of HDL metabolism, discuss clinical-trial data for HDL-raising agents, including possible reasons for the failure of torcetrapib, and consider the potential for future HDL-based therapies.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Amides
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Animals
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Anticholesteremic Agents / therapeutic use*
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Apolipoprotein A-I / genetics
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Apolipoprotein A-I / metabolism
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Atherosclerosis / genetics
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Atherosclerosis / metabolism
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Atherosclerosis / prevention & control*
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Cholesterol Ester Transfer Proteins / antagonists & inhibitors
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Clinical Trials as Topic
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Esters
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Humans
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Lipoproteins, HDL / chemistry
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Lipoproteins, HDL / metabolism*
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Lipoproteins, HDL / physiology
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Phospholipids / therapeutic use
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Quinolines / therapeutic use
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Sulfhydryl Compounds / therapeutic use
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Treatment Outcome
Substances
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Amides
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Anticholesteremic Agents
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Apolipoprotein A-I
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CETP protein, human
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Cholesterol Ester Transfer Proteins
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Esters
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Lipoproteins, HDL
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Phospholipids
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Quinolines
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Sulfhydryl Compounds
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dalcetrapib
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torcetrapib