title: Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients.
abstract: Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.
authors.affiliation: South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. Electronic address: stephen.nicholls@sahmri.com.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Ruotolo
authors.affiliation: Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington DC, USA.
authors.forename: H Bryan
authors.initials: HB
authors.lastname: Brewer
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Ming-Dauh
authors.initials: MD
authors.lastname: Wang
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Mark B
authors.initials: MB
authors.lastname: Willey
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Deeg
authors.affiliation: Eli Lilly and Company, Indianapolis, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Krueger
authors.affiliation: Cardiovascular Medicine, Cleveland Clinic, Cleveland, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Nissen
mesh_terms: D001569:Benzodiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood* / Q000737:chemistry; D004347:Drug Interactions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010316:Particle Size
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017270:Lipoprotein(a); D001569:Benzodiazepines; C568301:evacetrapib
keywords: CETP inhibitor; Evacetrapib; Hypercholesterolemia; LDL particle; Lipoprotein(a); Small LDL