Hospital Pharmacy - October 2017 - 596

729669
research-article2017

HPXXXX10.1177/0018578717729669Hospital PharmacyHu and Walker

Pharmaceutical Pipeline Update

Cholesterol Ester Transfer Protein
Inhibitor Review

Hospital Pharmacy
2017, Vol. 52(9) 596-598
© The Author(s) 2017
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https://doi.org/10.1177/0018578717729669
DOI: 10.1177/0018578717729669
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Jerry Hu1 and Scot Walker2

Abstract
Treatment of blood cholesterol is part of a strategy to lower atherosclerotic cardiovascular (ASCVD) risk. While use of
HMG-CoA reductase inhibitors to modify cholesterol levels is the primary means of lowering the risk of an ASCVD event,
residual risk remains. A new strategy being investigated is the use of cholesterol ester transfer protein (CETP) inhibitors
to raise the levels of high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C).
While initial large-scale studies demonstrated no reduction of cardiovascular events, one CETP inhibitor, anacetrapib, has
demonstrated a reduction in cardiovascular events in the REVEAL trial.
Keywords
investigational drugs, drug information, formulary management/P&T, cardiovascular

Epidemiology
Many meta-analyses have identified a correlation between
blood cholesterol levels and cardiovascular risk. Specifically,
decreasing low-density lipoprotein cholesterol (LDL-C),
decreasing triglycerides, and increasing high-density lipoprotein cholesterol (HDL-C) have been associated with
reduced risk for atherosclerotic cardiovascular events. Thus,
many drugs target these biomarkers to prevent atherosclerotic cardiovascular events.1

Current Treatment
HMG-CoA reductase inhibitors, also known as statins, lower
LDL-C and have demonstrated significant reduction in
reducing cardiovascular events.1 Guidelines from the
American College of Cardiology and the American Heart
Association on treating hyperlipidemia to reduce cardiovascular risk recommend initiating a statin depending on a
patient's risk factors and the 10-year risk for atherosclerotic
cardiovascular disease events.2 This initial strategy was reiterated in a recent commentary discussing new research and
therapies. Despite statins' efficacy, residual risk remains. As
statins' effect on non-LDL-C levels is limited, drugs targeting non-LDL-C levels may complement statins' benefit and
further reduce cardiovascular risk.1

with the goal of reducing residual risk of cardiovascular events
in high-risk patients on statins. CETP inhibitors mediate the
transfer of esterified cholesterol from HDL-C to atherogenic
lipoprotein particles, such as LDL-C, thereby raising HDL-C
and lowering LDL-C.3-5
Four CETP inhibitors have been studied in large phase III
prospective randomized control trials: torcetrapib, dalcetrapib, evacetrapib, and anacetrapib. Trials selected adult
patients with elevated cardiovascular risk, particularly those
with a history of atherosclerotic vascular disease. The treatment arm (CETP inhibitor + statin) was compared with a
control arm (placebo + statin). The primary outcomes were a
composite of major vascular events.4-6
Three of the 4 pivotal trials have finished. All of these trials found that CETP inhibitors displayed significant capacity
to raise HDL-C levels, ranging from an increase of 30% with
dalcetrapib to over 130% with evacetrapib. In spite of these
findings, the CETP inhibitors did not demonstrate a reduction in cardiovascular events compared with placebo.4-6 Due
to the failure to demonstrate efficacy in cardiovascular risk
reduction, development of torcetrapib, dalcetrapib, and evacetrapib has ceased.

1

St. Louis College of Pharmacy, MO, USA
Prescribe Right, LLC, Wildwood, MO, USA

2

New Treatment Options
Cholesterol ester transfer protein (CETP) inhibitors are a class
of drugs in the development pipeline which increase HDL-C

Corresponding Author:
Scot Walker, Chief Executive Officer, Prescribe Right, LLC, 1602
Westglen Farms Dr, Wildwood, MO 63011, USA.
Email: scot.walker@prescriberight.com
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