| Dalcetrapib: a review of Phase II data. | |
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MedLine Citation:
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PMID: 20465364 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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IMPORTANCE OF THE FIELD: While statins reduce the risk of cardiovascular disease by up to 50%, many patients remain at increased risk due to low levels of high-density lipoprotein cholesterol (HDL-C). Whether pharmacologically raising HDL-C per se with drug therapy will reduce cardiovascular events remains to be determined. AREAS COVERED IN THIS REVIEW: Review of HDL-C-raising compounds, with a focus on cholesteryl ester transfer protein (CETP) inhibitors. WHAT THE READER WILL GAIN: An overview of the CETP inhibitor dalcetrapib. Despite 70% increases in HDL-C, development of the CETP inhibitor torcetrapib was halted due to excess mortality, attributed largely to activation of the renin-angiotensin-aldosterone system resulting in hypertensive effects. Development of the CETP inhibitors dalcetrapib and anacetrapib is ongoing. Dalcetrapib has a unique chemical structure and induces a conformational change in CETP rather than forming a non-productive CETP/HDL-C complex as do the other CETP inhibitors. Although dalcetrapib is the least potent CETP inhibitor of the three in terms of CETP activity, the 900-mg dose did not increase blood pressure or raise aldosterone levels over 48 weeks of follow-up. The 600-mg dose of dalcetrapib is moving forward and raises HDL-C by 25 - 30% when used alone or in combination with a statin, with little effect on low-density lipoprotein cholesterol levels. TAKE HOME MESSAGE: Before regulatory approval is granted, results from the ongoing dal-OUTCOMES trial evaluating the effects of dalcetrapib 600 mg daily over standard statin therapy on mortality and morbidity in > 15,000 high-risk CHD patients will be needed. The Dalcetrapib HDL Evaluation, Atherosclerosis and Reverse Cholesterol Transport (dal-HEART) program also includes three surrogate end point trials, dal-VESSEL, dal-PLAQUE and dal-PLAQUE 2, which will provide further information as to the contribution of CETP to cardiovascular disease. |
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Authors:
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Jennifer G Robinson |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Expert opinion on investigational drugs Volume: 19 ISSN: 1744-7658 ISO Abbreviation: Expert Opin Investig Drugs Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-14 Completed Date: 2010-08-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9434197 Medline TA: Expert Opin Investig Drugs Country: England |
Other Details:
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Languages: eng Pagination: 795-805 Citation Subset: IM |
Affiliation:
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Lipid Research Clinic, University of Iowa, Iowa City, IA 52242, USA. jennifer-g-robinson@uiowa.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anticholesteremic Agents / adverse effects, pharmacokinetics, pharmacology* Cardiovascular Diseases / prevention & control Cholesterol Ester Transfer Proteins / antagonists & inhibitors Cholesterol, HDL / blood, drug effects* Clinical Trials, Phase II as Topic Humans Sulfhydryl Compounds / adverse effects, pharmacokinetics, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Anticholesteremic Agents; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Sulfhydryl Compounds; 0/dalcetrapib |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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