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 1, 1989·Circulation·D J GordonH A Tyroler
Aug 7, 1999·The New England Journal of Medicine·H B RubinsJ Wittes
Jun 13, 2001·Circulation·H Bloomfield RubinsUNKNOWN VA-HIT Study Group
May 8, 2002·Circulation·Greetje J de GroothJohn J P Kastelein
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
Jul 17, 2007·Lancet·Michiel L BotsUNKNOWN RADIANCE 2 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
Nov 18, 2009·British Journal of Pharmacology·E S G StroesE J Niesor
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
Sep 24, 2010·Journal of Lipid Research·Eric J NiesorCyrille Maugeais
Nov 19, 2010·The New England Journal of Medicine·Christopher P CannonUNKNOWN Determining the Efficacy and Tolerability Investigators
Dec 7, 2010·Current Medical Research and Opinion·John J P KasteleinThomas F Lüscher
Mar 2, 2011·Nature Reviews. Drug Discovery
Aug 13, 2011·American Heart Journal·Zahi A FayadMichael E Farkouh
Sep 13, 2011·Lancet·Zahi A FayadUNKNOWN dal-PLAQUE Investigators
Oct 1, 2011·Journal of Lipid Research·Guoqing CaoNathan B Mantlo
Nov 4, 2011·Postgraduate Medical Journal·Gerald F Watts, Fredrik Karpe
Nov 18, 2011·JAMA : the Journal of the American Medical Association·Stephen J NichollsSteven E Nissen