Document Detail


Safety of CETP inhibition.
MedLine Citation:
PMID:  23010697     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Cholesteryl ester transfer protein (CETP)-inhibiting drugs effectively raise HDL cholesterol. In 2007, the CETP inhibitor torcetrapib unexpectedly showed increased fatality and cardiovascular events, possibly related to increased blood pressure and aldosterone levels caused by torcetrapib. Since then, novel CETP inhibiting drugs have been investigated. This review will discuss the safety of the CETP-inhibiting drugs.
RECENT FINDINGS: The novel CETP inhibitors dalcetrapib, evacetrapib and anacetrapib did not show harmful effects on blood pressure or aldosterone levels. Ultrasound brachial artery flow-mediated vasodilation, carotid MRI and (18)F-fluordeoxyglucose PET imaging studies, showed that dalcetrapib therapy had neither harmful nor beneficial effects on endothelial function, atherosclerosis progression, or vessel wall inflammation. Recently, the clinical endpoint study investigating dalcetrapib was announced to be terminated early, after the second interim analysis showed that dalcetrapib lacked clinically meaningful efficacy.
SUMMARY: Dalcetrapib, evacetrapib and anacetrapib did not show the harmful effects on aldosterone and blood pressure that were exhibited by torcetrapib, indicating that CETP inhibition is well tolerated. So far CETP inhibition did not show beneficial effects on clinical outcome. The phase III study with anacetrapib will give final answers on whether CETP inhibition can reduce cardiovascular events.
Authors:
Raphaël Duivenvoorden; Zahi A Fayad
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current opinion in lipidology     Volume:  23     ISSN:  1473-6535     ISO Abbreviation:  Curr. Opin. Lipidol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-19     Completed Date:  2013-04-17     Revised Date:  2013-05-21    
Medline Journal Info:
Nlm Unique ID:  9010000     Medline TA:  Curr Opin Lipidol     Country:  England    
Other Details:
Languages:  eng     Pagination:  518-24     Citation Subset:  IM    
Affiliation:
Academic Medical Center, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzodiazepines / adverse effects,  pharmacology
Cholesterol Ester Transfer Proteins / antagonists & inhibitors*
Humans
Oxazolidinones / adverse effects,  pharmacology
Quinolines / adverse effects,  pharmacology
Safety*
Sulfhydryl Compounds / adverse effects,  pharmacology
Chemical
Reg. No./Substance:
0/Cholesterol Ester Transfer Proteins; 0/Oxazolidinones; 0/Quinolines; 0/Sulfhydryl Compounds; 12794-10-4/Benzodiazepines; 262352-17-0/torcetrapib; 3D050LIQ3H/dalcetrapib; 51XWV9K850/evacetrapib; P7T269PR6S/anacetrapib

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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