title: Efficacy and Safety of Evacetrapib for Modifying Plasma Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
abstract: BACKGROUND
  Evacetrapib, a new cholesteryl ester transfer protein inhibitor, is being investigated as a potential therapeutic option for reducing cardiovascular events through increasing high-density lipoprotein cholesterol (HDL-C) concentrations. How evacetrapib affects other lipid parameters is less certain. The present study aimed to estimate the effect of evacetrapib on plasma lipid concentrations and to assess its safety through a systematic review and meta-analysis of randomized controlled trials.
  
  
  METHODS
  SCOPUS, Medline, and Google Scholar were searched to identify randomized controlled trials investigating the impact of evacetrapib on blood lipid concentrations published before December 29, 2014. A random-effects model (using the DerSimonian-Laird method) and the generic inverse variance method were used to examine the effect of evacetrapib on plasma lipid concentrations. The safety of evacetrapib was assessed by comparing the pooled incidence of adverse events (total adverse events, adverse events leading to study discontinuation, elevations in hepatic and muscular enzymes and blood pressure) between treatment and placebo groups. Sensitivity analyses were conducted using the one study remove approach. Meta-regression was performed to evaluate the association between changes plasma lipid concentrations and administered doses of evacetrapib.
  
  
  RESULTS
  Meta-analysis of 14 randomized treatment arms over a mean of 2 months suggested that evacetrapib significantly reduces low-density lipoprotein cholesterol (LDL-C) (weighted mean difference [WMD]: -21.11%, 95% confidence interval (CI): -24.89, -17.33, p<0.001) and elevated HDL-C (WMD: +86.00%, 95% CI: +67.63, +104.37, p<0.001) concentrations following treatment with evacetrapib. Evacetrapib had no significant effect on plasma triglycerides (WMD: -2.97%, 95% CI: -8.63, +2.69, p = 0.303) concentrations. The effects of evacetrapib on all three lipid indices (LDL-C, HDL-C and triglycerides) did not differ between subsets of trials administering evacetrapib as monotherapy or as add-on to statin therapy. Meta-regression suggested a dose-dependent effect of evacetrapib on plasma LDL-C and HDL-C, but not triglycerides concentrations. Meta-analysis suggested equivalent rates of adverse events in subjects receiving evacetrapib and placebo.
  
  
  CONCLUSIONS
  Results of this meta-analysis suggested that evacetrapib, either as monotherapy or in combination with a statin, reduces LDL-C and increases HDL-C levels but has no effect on triglyceride concentrations. Adverse events appeared to be similar in subjects receiving evacetrapib and placebo in short-term follow-ups.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Predio Canoas 100, Col. Los Angeles 34067, Durango, Dgo., Mexico. luis_simental81@hotmail.com.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.forename: Fernando
authors.initials: F
authors.lastname: Guerrero-Romero
authors.forename: Jonathan
authors.initials: J
authors.lastname: Golledge
authors.affiliation: School of Medicine and Pharmacology University of Western Australia, GPO Box X2213, Perth, WA6847, Australia. Gerald.watts@uwa.edu.au.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D006801:Humans; D008055:Lipids / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D012449:Safety
chemical_list: D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D001569:Benzodiazepines; C568301:evacetrapib