title: Current status of CETP inhibitors in the treatment of hyperlipidemia: an update.
abstract: BACKGROUND
  The inverse relationship between HDL-C and cardiovascular disease risk suggests that increasing HDL-C could potentially reduce the disease risk. Reverse cholesterol transport is considered to be the primary mechanism by which HDL-C exerts its anti-atherogenic effects. A key regulator of RCT is cholesteryl ester transfer protein (CETP).
  
  
  METHODS
  Inhibition of CETP has been identified as a possible strategy for substantially increasing HDL-C levels and CETP inhibitors have demonstrated clinical efficacy in preliminary clinical trials. The development of this novel class suffered a major setback when the major phase 3 trial of torcetrapib, the first CETP inhibitior was prematurely terminated due to an increase in cardiovascular and noncardiovascular mortality. Subsequent animal and clinical studies have shown that the increase in cardiovascular mortality reported with torcetrapib was molecule specific and independent of its CETP inhibition effect. The other two CETP inhibitors i.e. dalcetrapib and anacetrapib were well tolerated in phase I and II clinical trials and unlike torcetrapib, did not affect blood pressure and aldosterone levels. In this review article the authors have discussed the lessons learned from torcetrapib failure and important preclinical and clinical developments of CETP inhibitors and their role in management of hyperlipidemia and cardiovascular risk reduction.
authors.affiliation: Department of Pharmacology, Maulana Azad Medical College, New Delhi, India. dr.raktimghosh@gmail.com
authors.forename: Raktim Kumar
authors.initials: RK
authors.lastname: Ghosh
authors.forename: Samhati Mondal
authors.initials: SM
authors.lastname: Ghosh
mesh_terms: D000577:Amides; D000818:Animals; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000517:prevention & control; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D008076:Cholesterol, HDL / Q000097:blood; D004952:Esters; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy*; D023303:Oxazolidinones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000577:Amides; D000924:Anticholesteremic Agents; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D004952:Esters; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; C411602:dalcetrapib; C483909:torcetrapib; C530884:anacetrapib