Effects of dalcetrapib on vascular function: results of phase iibdal-vessel study

Results of the phase IIb dal-VESSEL study show that dalcetrapib, aninvestigational molecule which acts on cholesteryl ester transferprotein (CETP), did not impair endothelial function (as indicatedby flow-mediated dilatation) or increase blood pressure, and wasgenerally well tolerated in patients with or at risk of coronary heart disease . “The results provide important information regarding the safety ofthis novel molecule,” said principal investigator Professor ThomasF. L scher from the University Hospital, Zurich, Switzerland. Headded that dal-VESSEL was the largest multicentre trial everperformed with brachial flow-mediated dilatation measured as amarker of endothelial function and cardiovascular risk. Panel Mount Keyboard

Dal-VESSEL was an exploratory phase IIb randomised, double-blind,placebo-controlled trial in patients with coronary heart disease(CHD), or CHD risk equivalents, in which 476 patients with HDL-Clevels 50 mg/dL were recruited. They received dalcetrapib 600mg/day or placebo in addition to their existing treatments. Theprimary efficacy endpoint was change from baseline in brachial flowmediated dilation after 12 weeks. The primary safety endpoint was24-hour ambulatory blood pressure monitoring assessed at week four.Patients were treated for a total period of 36 weeks. China Children Color Keyboard

Results showed that dalcetrapib reduced CETP activity by almost 50%and increased high-density lipoprotein cholesterol (HDL-C) levels by 31% without changing nitric-oxide-dependentendothelial function or markers of inflammation and oxidative stress . No safety signals were observed during the whole study, and 23pre-specified positively adjucated events occurred with an evendistribution in both treatement arms (11 with dalcetrapib and 12with placebo). Dalcetrapib raises functional HDL-C by modulating CETP activitythrough a mechanism which differs from other CETP inhibitors, and,in earlier experimental studies, promoted efflux of cholesterolfrom cells. The hypothesis that it will similarly removecholesterol from atherosclerotic plaques in humans, potentiallyreducing the occurrence of cardiovascular events, is currentlybeing tested in phase III studies. Results of a second phase 2b study of dalcetrapib, dal-PLAQUE,showed similarly “encouraging” results in atherosclerotic diseaseprogression – no evidence of pro-inflammatory effects as measuredby positron emission tomography/computed tomography (PET/CT) at sixmonths, nor on plaque progression measured by magnetic resonanceimaging after 12 months. Plastic Industrial Keyboard Manufacturer

“High density lipoprotein removes cholesterol from atheroscleroticplaques,” said L scher, “so drugs which improve this functionalitymay slow the progression of atherosclerosis and preventcardiovascular events. Results so far suggest that dalcetrapib doesnot have pro-inflammatory or pro-atherogenic effects, does notaffect blood pressure and is generally well tolerated by patientstreated for up to two years.” Authors: Professor L scher, Thomas F (Zurich, Switzerland) Additional References Citations.

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