TY  - BOOK
AU  - Brewer, H Bryan
TI  - Cholesterol Efflux Capacity and Pre-Beta-1 HDL Concentrations Are Increased in Dyslipidemic Patients Treated With Evacetrapib
SN  - 0735-1097
PY  - 2015///
KW  - *Anticholesteremic Agents/tu [Therapeutic Use]
KW  - *Benzodiazepines/tu [Therapeutic Use]
KW  - *Cholesterol/bl [Blood]
KW  - *Dyslipidemias/dt [Drug Therapy]
KW  - *High-Density Lipoproteins, Pre-beta/bl [Blood]
KW  - *Hydroxymethylglutaryl-CoA Reductase Inhibitors/tu [Therapeutic Use]
KW  - ATP Binding Cassette Transporter 1/me [Metabolism]
KW  - Cholesterol Ester Transfer Proteins/ai [Antagonists & Inhibitors]
KW  - Cholesterol Ester Transfer Proteins/me [Metabolism]
KW  - Double-Blind Method
KW  - Drug Therapy, Combination
KW  - Dyslipidemias/bl [Blood]
KW  - Female
KW  - Humans
KW  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/ad [Administration & Dosage]
KW  - Male
KW  - Middle Aged
KW  - MedStar Health Research Institute
KW  - Clinical Trial, Phase II
KW  - Journal Article
KW  - Multicenter Study
KW  - Randomized Controlled Trial
N1  - Available online from MWHC library: 1995 - present, Available in print through MWHC library:1999-2007
N2  - BACKGROUND: Potent cholesteryl ester transfer protein (CETP) inhibitors have been shown to substantially increase high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels as monotherapy and combined with statins. However, data on the effects of this class of drugs on macrophage cholesterol efflux capacity (CEC), a functional assay that characterizes a key step in the process of reverse cholesterol transport, are limited; CONCLUSIONS: Evacetrapib, as monotherapy and combined with statins, not only increased total CEC, but also increased ABCA1-specific CEC and pre-beta-1 HDL. The mechanisms by which potent CETP inhibition increases ABCA1-specific CEC and pre-beta-1 HDL require further study. (A Study of LY2484595 in Patients With High LDL-C or Low HDL-C; NCT01105975).Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved; METHODS: We analyzed samples from 377 subjects with elevated low-density lipoprotein cholesterol (LDL-C) or low HDL-C levels who were enrolled in a phase 2 trial of evacetrapib. Percent changes from baseline in CEC (total, non-ABCA1-, and ABCA1-specific) and HDL subpopulations were evaluated after 12 weeks of treatment with placebo, statin monotherapy, evacetrapib monotherapy, or evacetrapib combined with statins. Pre-beta-1 HDL levels were quantified by immunofixation and nondenaturing 2-dimensional gel electrophoresis (2DGE); OBJECTIVES: This study assessed the impact of evacetrapib, statins, or combination therapy on CEC; RESULTS: Relative to placebo, evacetrapib monotherapy increased dose-dependent total and non-ABCA1-specific CEC up to 34% and 47%, respectively. Evacetrapib monotherapy also increased ABCA1-specific CEC up to 26%. Relative to statin monotherapy, evacetrapib with statins also increased total, non-ABCA1-, and ABCA1-specific CEC by 21%, 27%, and 15%, respectively. In contrast, rosuvastatin and simvastatin significantly reduced total and ABCA1-specific CEC, whereas atorvastatin had no significant effect. Consistent with ABCA1-specific CEC, evacetrapib monotherapy and evacetrapib combined with statins significantly increased pre-beta-1 HDL levels as measured by either method
UR  - http://dx.doi.org/10.1016/j.jacc.2015.09.013
ER  -