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 lowdensity
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.
Conclusion. 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.