Title:Current Status of CETP Inhibitors in the Treatment of Hyperlipidemia: An Update
Volume: 7
Issue: 2
Author(s): Raktim Kumar Ghosh and Samhati Mondal Ghosh
Affiliation:
Keywords:
Anacetrapib, CETP inhibitors, dalcetrapib, HDL cholesterol, reverse cholesterol transport, torcetrapib
Abstract: Introduction: The inverse relationship between HDL-C and cardiovascular disease risk suggests that
increasing HDL-C could potentially reduce the disease risk. Reverse cholesterol transport is considered to be the primary
mechanism by which HDL-C exerts its anti-atherogenic effects. A key regulator of RCT is cholesteryl ester transfer
protein (CETP).
Areas Covered: Inhibition of CETP has been identified as a possible strategy for substantially increasing HDL-C levels
and CETP inhibitors have demonstrated clinical efficacy in preliminary clinical trials. The development of this novel class
suffered a major setback when the major phase 3 trial of torcetrapib, the first CETP inhibitior was prematurely terminated
due to an increase in cardiovascular and noncardiovascular mortality. Subsequent animal and clinical studies have shown
that the increase in cardiovascular mortality reported with torcetrapib was molecule specific and independent of its CETP
inhibition effect. The other two CETP inhibitors i.e. dalcetrapib and anacetrapib were well tolerated in phase I and II
clinical trials and unlike torcetrapib, did not affect blood pressure and aldosterone levels.
In this review article the authors have discussed the lessons learned from torcetrapib failure and important preclinical and
clinical developments of CETP inhibitors and their role in management of hyperlipidemia and cardiovascular risk
reduction.
