title: Anacetrapib for the treatment of dyslipidaemia: the last bastion of the cholesteryl ester transfer protein inhibitors?
abstract: BACKGROUND
  Inhibition of cholesteryl ester transfer protein (CETP) has emerged as a potential way to decrease cardiovascular risk by raising high density lipoprotein (HDL) cholesterol and lowering low density lipoprotein (LDL) cholesterol concentrations. However, high profile withdrawals of several CETP inhibitors have cast doubt over this hypothesis. Despite this concern, anacetrapib appears to be safe, well-tolerated and delivers a substantial increases in HDL cholesterol and reductions in LDL cholesterol as monotherapy and when combined with a statin.
  
  
  METHODS
  We discuss the role of CETP and HDL cholesterol as therapeutic targets, describe the pharmacokinetics and pharmacodynamics of anacetrapib, as well as report on the recent clinical trials.
  
  
  CONCLUSIONS
  The focus of CETP inhibition has shifted from HDL cholesterol-raising to LDL cholesterol-lowering. Although anacetrapib appears to be safe and is effective in altering lipid-related biochemical parameters of interest, its effect on cardiovascular outcomes remains unknown. Extrapolation of LDL cholesterol lowering to improved cardiovascular outcomes is not possible, because LDL and HDL functionality in the setting of anacetrapib treatment is unclear. The results of the phase III REVEAL randomised controlled trial will be critical for anacetrapib to establish a place in clinical care.
authors.affiliation: a Department of Clinical Biochemistry, PathWest Laboratory Medicine WA , Royal Perth Hospital and Fiona Stanley Hospital Network , Perth , Australia.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Page
authors.affiliation: a Department of Clinical Biochemistry, PathWest Laboratory Medicine WA , Royal Perth Hospital and Fiona Stanley Hospital Network , Perth , Australia.|b School of Medicine & Pharmacology , University of Western Australia , Perth , Australia.|c School of Pathology & Laboratory Medicine , University of Western Australia , Perth , Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.affiliation: a Department of Clinical Biochemistry, PathWest Laboratory Medicine WA , Royal Perth Hospital and Fiona Stanley Hospital Network , Perth , Australia.|b School of Medicine & Pharmacology , University of Western Australia , Perth , Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058990:Molecular Targeted Therapy; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D023303:Oxazolidinones; C530884:anacetrapib
keywords: Anacetrapib; apolipoprotein A-I; atherosclerosis; cardiovascular disease; cholesteryl ester transfer protein inhibitors; high density lipoprotein; low density lipoprotein