Document Detail

Acute and short-term effects of the nonpeptide endothelin-1 receptor antagonist bosentan in humans.
MedLine Citation:
PMID:  9110115     Owner:  NLM     Status:  MEDLINE    
In recent years, evidence from various animals 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.
G Sütsch; O Bertel; W Kiowski
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy     Volume:  10     ISSN:  0920-3206     ISO Abbreviation:  Cardiovasc Drugs Ther     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-07-02     Completed Date:  1997-07-02     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  8712220     Medline TA:  Cardiovasc Drugs Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  717-25     Citation Subset:  IM    
Division of Cardiology, University and Triemli Hospitals, Zürich, Switzerland.
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MeSH Terms
Administration, Oral
Blood Pressure / drug effects
Chronic Disease
Double-Blind Method
Heart Failure / drug therapy*
Hemodynamics / drug effects*
Middle Aged
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors*
Sulfonamides / therapeutic use*
Time Factors
Vascular Resistance / drug effects
Reg. No./Substance:
0/Receptor, Endothelin A; 0/Receptors, Endothelin; 0/Sulfonamides; Q326023R30/bosentan

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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