Congestive heart failure darusentan
Congestive heart failure continues to be a major cause of death in the industrialised world. Bad diet, lack of exercise and smoking are all contributory factors and the market for new drugs to treat hypertension and heart failure is enormous.
Congestive heart failure continues to be a major cause of death in the industrialised world. Bad diet, lack of exercise and smoking are all contributory factors and the market for new drugs to treat hypertension and heart failure is enormous.
One mechanism by which high blood pressure can be remedied is by blocking the action of the peptide endothelin. Endothelial cells line the whole of the body's vascular system, and for many years were believed merely to provide a physical barrier to stop blood cells and other plasma constituents from penetrating the surrounding tissues. However, it was later established that they produce numerous active substances that are involved in the contraction of vascular smooth muscle and, ultimately, in raising the blood pressure. Endothelin is the most potent of these substances, and plays a vital role in the pathogenesis of vascular disorders, particularly hypertension and heart failure.1
As a result, selective endothelin antagonists have become a target for drug discovery, and one compound in this class that is being developed by Abbott is darusentan. The endothelin ETA receptor antagonist has been investigated in a multi-centre, double blind, randomised, placebo controlled clinical trial in 157 patients suffering from congestive heart failure.2,3
Patients were given darusentan in oral doses of 30, 100 or 300 mg/day, or placebo, over a period of three weeks in addition to their normal drug regime. All three doses resulted in an improved cardiac index, which improved further with long term treatment.
A further study looked at the effects of darusentan on endothelial function in a group of 21 patients with congestive heart failure.4 They were given placebo, or 30 or 300mg/day of darusentan for three weeks, and the ability of the patients' blood vessels to dilate was measured. The 14 patients given darusentan all showed improved vasodilation, and this preliminary study shows that it could be of use in improving flow-mediated vasodilation in patients with congestive heart failure.