| Reference | 1. Cardiol Rev. 2017 Mar/Apr;25(2):43-52. doi: 10.1097/CRD.0000000000000137.
<br>
Evacetrapib: Another CETP Inhibitor for Dyslipidemia With No Clinical Benefit.
<br>
Eyvazian VA(1), Frishman WH.
<br>
Author information: <br>
(1)From the *Department of Medicine, Ronald Reagan UCLA Medical Center, Los
Angeles, CA; and †Department of Medicine, New York Medical College/Westchester
Medical Center, Valhalla, NY.
<br>
Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has
been recently studied as a cholesterol modifying agent to reduce cardiovascular
risk and mortality in high risk cardiovascular disease patients. Evacetrapib acts
to decrease lipid exchange through CETP inhibition. CETP acts to transfer
cholesteryl esters from high-density lipoprotein-cholesterol (HDL-C) to
low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein
(VLDL-C). HDL-C is involved in reverse cholesterol transport and its blood levels
have been shown to be inversely correlated with cardiovascular risk. Thus, a
pharmacologic agent that can elevate HDL-C has been seen as an exciting area of
research. In recent studies, evacetrapib was shown to be safe and efficacious. It
produced an increase in HDL-C up to 128% and a 35% decrease in LDL-C, in
comparison to placebo. In addition, evacetrapib was also shown to be more potent
than previous CETP inhibitors. HDL-C particles treated with evacetrapib remained
functional and had improved cholesterol efflux. A previously studied CETP
inhibitor, torcetrapib, exhibited side effects of hyperaldosteronism, manifesting
in electrolyte disturbances, and hypertension. These detrimental effects were not
seen with evacetrapib. Recently, the results of evacetrapib/’s phase III
ACCELERATE trial showed no significant reduction in major adverse cardiovascular
events or mortality, and the drug will not be marketed. Although beneficial
cholesterol effects were seen with this drug, more needs to be known to
understand what role, if any, evacetrapib has in the reduction of cardiovascular
risk.
<br>
2. Curr Pharm Des. 2016;22(5):595-608.
<br>
Efficacy and Safety of Evacetrapib for Modifying Plasma Lipids: A Systematic
Review and Meta-Analysis of Randomized Controlled Trials.
<br>
Sahebkar A, Simental-Mendía LE(1), Guerrero-Romero F, Golledge J, Watts GF(2).
<br>
Author information: <br>
(1)Predio Canoas 100, Col. Los Angeles 34067, Durango, Dgo., Mexico.
[email protected].
(2)School of Medicine and Pharmacology University of Western Australia, GPO Box
X2213, Perth, WA6847, Australia. [email protected].
<br>
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.<br>
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.<br>
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.<br>
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.
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