title: Safety of CETP inhibition.
abstract: OBJECTIVE
  Cholesteryl ester transfer protein (CETP)-inhibiting drugs effectively raise HDL cholesterol. In 2007, the CETP inhibitor torcetrapib unexpectedly showed increased fatality and cardiovascular events, possibly related to increased blood pressure and aldosterone levels caused by torcetrapib. Since then, novel CETP inhibiting drugs have been investigated. This review will discuss the safety of the CETP-inhibiting drugs.
  
  
  RESULTS
  The novel CETP inhibitors dalcetrapib, evacetrapib and anacetrapib did not show harmful effects on blood pressure or aldosterone levels. Ultrasound brachial artery flow-mediated vasodilation, carotid MRI and (18)F-fluordeoxyglucose PET imaging studies, showed that dalcetrapib therapy had neither harmful nor beneficial effects on endothelial function, atherosclerosis progression, or vessel wall inflammation. Recently, the clinical endpoint study investigating dalcetrapib was announced to be terminated early, after the second interim analysis showed that dalcetrapib lacked clinically meaningful efficacy.
  
  
  CONCLUSIONS
  Dalcetrapib, evacetrapib and anacetrapib did not show the harmful effects on aldosterone and blood pressure that were exhibited by torcetrapib, indicating that CETP inhibition is well tolerated. So far CETP inhibition did not show beneficial effects on clinical outcome. The phase III study with anacetrapib will give final answers on whether CETP inhibition can reduce cardiovascular events.
authors.affiliation: Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Duivenvoorden
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000577:Amides; D000818:Animals; D001569:Benzodiazepines / Q000009:adverse effects / Q000494:pharmacology; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors*; D004952:Esters; D006801:Humans; D023303:Oxazolidinones / Q000009:adverse effects / Q000494:pharmacology; D011804:Quinolines / Q000009:adverse effects / Q000494:pharmacology; D012449:Safety; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000494:pharmacology
chemical_list: D000577:Amides; D053480:Cholesterol Ester Transfer Proteins; D004952:Esters; D023303:Oxazolidinones; D011804:Quinolines; D013438:Sulfhydryl Compounds; D001569:Benzodiazepines; C411602:dalcetrapib; C483909:torcetrapib; C568301:evacetrapib; C530884:anacetrapib