The effect of bosentan on endothelial function in patients with congestive heart failure

Abstract

Background Increased endothelin concentrations are one mechanism underlying endothelial dysfunction. Congestive heart failure (CHF) is characterized by increased levels of endothelin and endothelial dysfunction. Bosentan (BOS), a dual endothelin receptor blocker, have beneficial hemodynamic effects in patients with heart failure, but its effects on endothelial function are not known. Methods In a randomized, double blind, placebo controlled study we examined the effects of escalating doses of BOS (from 8mg to 240mg) on endothelial function in 22 patients with CHF (6 placebo, 16 BOS, 15 men, age: 71±2 years, ejection fraction: 29±1%). All patients were also treated with diuretics, beta-blockers and either ACE-inhibitors or angiotensin-receptor blockers. Endothelial function was assessed non-invasively at baseline and the last visit by measurement of central blood pressure and augmentation index using a semi-automated pulse wave analysis system. Results BOS resulted in a significant decrease in central systolic (−12±5 mmHg, p=0.03) and diastolic pressure (−12±3 mmHg, p=0.003) but augmentation index remained unchanged (from 27±3% at baseline to 24±3% after BOS, P=0.3). Time to reflection (a measure of pulse wave velocity) was unaffected by BOS treatment (from 141±3 msec to 144±4 msec, P=0.5). Placebo had no significant effect on any parameter. Conclusions BOS, added to standard therapy for CHF, decreased blood pressure but had no effect on endothelial function. Clinical Pharmacology & Therapeutics (2005) 77, P12–P12; doi: 10.1016/j.clpt.2004.11.047