Dalcetrapib--restoring belief in modulating CETP as a beneficial mechanism in cardiovascular disease

Expert Opinion on Investigational Drugs
Sheila A Doggrell

Abstract

As low HDL cholesterol levels are a risk factor for cardiovascular disease, raising HDL cholesterol substantially by inhibiting or modulating cholesteryl ester transfer protein (CETP) may be useful in coronary artery disease. The first CETP inhibitor that went into clinical trial, torcetrapib, was shown to increase the levels of HDL cholesterol, but it also increased cardiovascular outcomes, probably due to an increase in blood pressure and aldosterone secretion, by an off-target mechanism/s. Dalcetrapib is a new CETP modulator that increases the levels of HDL cholesterol, but does not increase blood pressure or aldosterone secretion. The objective was to evaluate a paper describing the effects of dalcetrapib on carotid and aortic wall thickness in subjects with, or at high risk of, coronary artery disease, the dal-PLAQUE study. dal-PLAQUE showed that dalcetrapib reduced the progression of atherosclerosis and may also reduce the vascular inflammation associated with this, in subjects with, or with high risk of, coronary heart disease, who were already taking statins. These results suggest that modulating CETP with dalcetrapib may be a beneficial mechanism in cardiovascular disease. The results of the dal-HEART series, which inc...Continue Reading

References

Jan 26, 2006·Expert Opinion on Investigational Drugs·Sheila A Doggrell
Mar 28, 2007·The New England Journal of Medicine·Steven E NissenUNKNOWN ILLUSTRATE Investigators
Mar 28, 2007·The New England Journal of Medicine·John J P KasteleinUNKNOWN RADIANCE 1 Investigators
Apr 2, 2008·Expert Opinion on Pharmacotherapy·Sheila A Doggrell
Jul 7, 2009·The American Journal of Cardiology·Evan A SteinJohn J P Kastelein
Dec 5, 2009·American Heart Journal·Gregory G SchwartzUNKNOWN dal-OUTCOMES Committees and Investigators
Jan 26, 2010·European Heart Journal·Evan A SteinJennifer G Robinson
Jun 4, 2010·European Journal of Clinical Pharmacology·Michael DerksGeorgina Meneses-Lorente
Nov 19, 2010·The New England Journal of Medicine·Christopher P CannonUNKNOWN Determining the Efficacy and Tolerability Investigators
Mar 2, 2011·Nature Reviews. Drug Discovery

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.