title: The effect of cholesteryl ester transfer protein inhibition on lipids, lipoproteins, and markers of HDL function after an acute coronary syndrome: the dal-ACUTE randomized trial.
abstract: OBJECTIVE
  The effects of cholesteryl ester transfer protein (CETP) inhibition on lipids, inflammation, and markers of high-density lipoprotein (HDL) function, following an acute coronary syndrome (ACS), are unknown.
  
  
  RESULTS
  The dal-ACUTE study randomized 300 patients (1 : 1) to dalcetrapib 600 mg/day or placebo within 1 week of an ACS. The primary endpoint was per cent change in HDL-cholesterol (HDL-C) after 4 weeks. Secondary endpoints included apolipoprotein levels, markers of HDL function, and inflammation. Dalcetrapib treatment increased HDL-C and apolipoprotein A1 by 33.7 and 11.8%, respectively (both P < 0.001) and total cholesterol efflux by 9.5% (P = 0.003) after 4 weeks, principally via an increase in non-ATP-binding cassette transporter (ABC) A1-mediated efflux, without statistically significant changes in pre-β1-HDL levels. The increase in total efflux with dalcetrapib correlated most strongly with increases in apolipoprotein A1 and HDL-C (r = 0.46 and 0.43, respectively) rather than the increase in pre-β1-HDL (r = 0.32). Baseline and on-treatment ABCA1-mediated efflux correlated most strongly with pre-β1-HDL levels; in contrast, non-ABCA1-mediated efflux correlated better with apolipoprotein A1 and HDL-C levels.
  
  
  CONCLUSIONS
  High-density lipoprotein raised through CETP inhibition with dalcetrapib improves cholesterol efflux, principally via a non-ABCA1-mediated pathway. While HDL-C was increased by one-third, apolipoprotein A1 and total efflux were increased only by one-tenth, supporting the concept of dissociation between improvements in HDL function and HDL-C levels, which may be of relevance to ongoing trials and the development of therapeutic interventions targeting HDL.
authors.affiliation: Cardiovascular Sciences Research Centre, St George's University of London, Cranmer Terrace, London, SW17 ORE UK kray@sgul.ac.uk.
authors.forename: Kausik K
authors.initials: KK
authors.lastname: Ray
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Ditmarsch
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Kallend
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Niesor
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Suchankova
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Upmanyu
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Anzures-Cabrera
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lehnert
authors.affiliation: F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Meike
authors.initials: M
authors.lastname: Pauly-Evers
authors.affiliation: Department of Endocrinology, Obesity and Preventive Medicine, Oslo University Hospital, Ulleval, Oslo, Norway.
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.affiliation: Charles University Faculty Hospital, Hradec Králové, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Štásek
authors.affiliation: Groene Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Maarten W J
authors.initials: MW
authors.lastname: van Hessen
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000577:Amides; D000789:Angina, Unstable / Q000188:drug therapy; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D001053:Apolipoproteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000378:metabolism; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004952:Esters; D005260:Female; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D013438:Sulfhydryl Compounds / Q000008:administration & dosage*
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000577:Amides; D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004952:Esters; D008074:Lipoproteins; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; D002097:C-Reactive Protein
keywords: Coronary disease; Lipids; Lipoproteins