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J Clin Lipidol. 2016 May-Jun;10(3):519-527.e4. doi: 10.1016/j.jacl.2015.11.014. Epub 2015 Dec 18.

Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients.

Author information

1
South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. Electronic address: stephen.nicholls@sahmri.com.
2
Eli Lilly and Company, Indianapolis, USA.
3
Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington DC, USA.
4
Cardiovascular Medicine, Cleveland Clinic, Cleveland, USA.

Abstract

BACKGROUND:

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.

OBJECTIVES:

To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients.

METHODS:

VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30 mg/d, 100 mg/d, or 500 mg/d) or in combination with statins (100 mg plus simvastatin 40 mg/d, atorvastatin 20 mg/d, or rosuvastatin 10 mg/d; Clinicaltrials.gov Identifier: NCT01105975).

RESULTS:

Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500 mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000 nmol/L) and sLDL (>600 nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size.

CONCLUSIONS:

Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

KEYWORDS:

CETP inhibitor; Evacetrapib; Hypercholesterolemia; LDL particle; Lipoprotein(a); Small LDL

PMID:
27206939
DOI:
10.1016/j.jacl.2015.11.014
[Indexed for MEDLINE]

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