title: Cholesteryl ester transfer protein inhibitors: challenges and perspectives.
abstract: BACKGROUND
  Cholesteryl ester transfer protein (CETP) inhibitors substantially increase the concentration of high-density lipoprotein cholesterol (HDL-C), which may have a possible beneficial effect for cardiovascular disease risk reduction.
  
  
  METHODS
  Current data regarding the effects of CETP inhibitors on cardiovascular disease risk and possible mechanisms for their effects and safety are presented in this review. Expert commentary: The first CETP inhibitor, torcetrapib, was discontinued because of increased off-target adverse effects (increased serum aldosterone and blood pressure levels). The development program of dalcetrapib and evacetrapib, which were not associated with increased blood pressure, was terminated due to futility (insufficient efficacy) concerning cardiovascular outcomes. Although the failure of torcetrapib has been attributed to specific off-target effects, there are some common characteristics between CETP inhibitors pointing to the possibility that certain adverse effects may be class-specific. The newer CETP inhibitors anacetrapib and TA-8995 have promising effects on lipid profile and metabolism (increase of HDL-C and reduction of both low-density lipoprotein cholesterol and lipoprotein (a) levels), but their cardiovascular effects and safety profile have not yet been confirmed in large outcome trials.
authors.affiliation: a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece.
authors.forename: T D
authors.initials: TD
authors.lastname: Filippatos
authors.affiliation: a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece.
authors.forename: E
authors.initials: E
authors.lastname: Klouras
authors.affiliation: a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece.
authors.forename: F
authors.initials: F
authors.lastname: Barkas
authors.affiliation: a Department of Internal Medicine, School of Medicine , University of Ioannina , Ioannina , Greece.
authors.forename: M
authors.initials: M
authors.lastname: Elisaf
mesh_terms: D000577:Amides; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004952:Esters; D006801:Humans; D008055:Lipids / Q000097:blood*; D017270:Lipoprotein(a) / Q000097:blood; D008075:Lipoproteins, HDL / Q000378:metabolism; D023303:Oxazolidinones / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D013438:Sulfhydryl Compounds / Q000627:therapeutic use
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004952:Esters; D008055:Lipids; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; C000597751:TA-8995; D001569:Benzodiazepines; C411602:dalcetrapib; C483909:torcetrapib; C568301:evacetrapib; C530884:anacetrapib
keywords: Cholesteryl ester transfer protein inhibitors; TA-8995; anacetrapib; cardiovascular disease; dalcetrapib; evacetrapib; torcetrapib