Header

UZH-Logo

Maintenance Infos

Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans


Sütsch, Gabor; Bertel, Osmund; Kiowski, Wolfgang (1997). Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans. Cardiovascular Drugs and Therapy, 10(6):717-725.

Abstract

In recent years, evidence from various animal experiments has accumulated that emphasizes the role of endothelin-1 in the pathophysiology of several cardiovascular diseases, including congestive heart failure. The recent advent of potent antagonists of this system now allows the assessment of the involvement of endothelin-1 in the maintenance of vascular tone in animals and humans. We report hemodynamic data from two trails in patients with chronic severe congestive heart failure (i.e., reduced left ventricular ejection fraction of <30%, elevated resting pulmonary capillary wedged pressure >15 mmHg, and/or reduced cardiac index of 2.5 L/min/m2 or less) who were treated with the mixed endothelin-type A and type B-receptor antagonist bosentan. In the first study, the acute effect of bosentan (300 mg, intravenous) on hemodynamics and neurohormones was investigated. Bosentan was well tolerated and significantly improved impaired hemodynamics due to systemic and venous vasodilation. In the second trial, bosentan was given orally (0.5 g bid) for 14 days, in addition to conventional triple treatment for congestive heart failure, including digitalis, angiotensin-converting enzyme inhibitors, and diuretics. Cardiac hemodynamics were monitored during the first 24 hours of treatment, and measurements were repeated during the last day of bosentan therapy. Bosentan was well tolerated in these patients as well, and hemodynamic measures were compatible with an additional effect of bosentan after 2 weeks. However, there was a slight increase in heart rate as well. Our result underline the importance of endogenously generated endothelin-1 in congestive heart failure and suggest a potential benefit of endothelin antagonism in such patients. However, long-term studies are needed to establish whether chronic endothelin antagonism has beneficial clinical effects and is capable of improving survival and/or symptoms in severe heart failure patients who remain symptomatic despite standard triple therapy

Abstract

In recent years, evidence from various animal experiments has accumulated that emphasizes the role of endothelin-1 in the pathophysiology of several cardiovascular diseases, including congestive heart failure. The recent advent of potent antagonists of this system now allows the assessment of the involvement of endothelin-1 in the maintenance of vascular tone in animals and humans. We report hemodynamic data from two trails in patients with chronic severe congestive heart failure (i.e., reduced left ventricular ejection fraction of <30%, elevated resting pulmonary capillary wedged pressure >15 mmHg, and/or reduced cardiac index of 2.5 L/min/m2 or less) who were treated with the mixed endothelin-type A and type B-receptor antagonist bosentan. In the first study, the acute effect of bosentan (300 mg, intravenous) on hemodynamics and neurohormones was investigated. Bosentan was well tolerated and significantly improved impaired hemodynamics due to systemic and venous vasodilation. In the second trial, bosentan was given orally (0.5 g bid) for 14 days, in addition to conventional triple treatment for congestive heart failure, including digitalis, angiotensin-converting enzyme inhibitors, and diuretics. Cardiac hemodynamics were monitored during the first 24 hours of treatment, and measurements were repeated during the last day of bosentan therapy. Bosentan was well tolerated in these patients as well, and hemodynamic measures were compatible with an additional effect of bosentan after 2 weeks. However, there was a slight increase in heart rate as well. Our result underline the importance of endogenously generated endothelin-1 in congestive heart failure and suggest a potential benefit of endothelin antagonism in such patients. However, long-term studies are needed to establish whether chronic endothelin antagonism has beneficial clinical effects and is capable of improving survival and/or symptoms in severe heart failure patients who remain symptomatic despite standard triple therapy

Statistics

Citations

Dimensions.ai Metrics
56 citations in Web of Science®
65 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

33 downloads since deposited on 05 Dec 2018
13 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Pharmacology
Health Sciences > Cardiology and Cardiovascular Medicine
Health Sciences > Pharmacology (medical)
Uncontrolled Keywords:Pharmacology (medical), Pharmacology, Cardiology and Cardiovascular Medicine, General Medicine
Language:English
Date:1 January 1997
Deposited On:05 Dec 2018 19:29
Last Modified:15 Apr 2021 14:53
Publisher:Springer
ISSN:0920-3206
OA Status:Green
Publisher DOI:https://doi.org/10.1007/bf00053029
PubMed ID:9110115

Download

Green Open Access

Download PDF  'Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans'.
Preview
Content: Published Version
Language: English
Filetype: PDF (Nationallizenz 142-005)
Size: 857kB
View at publisher