Document Detail


Hemodynamic effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with class III to IV congestive heart failure.
MedLine Citation:
PMID:  11181472     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Endothelin-1, a powerful mediator of vasoconstriction, is increased in patients with congestive heart failure and appears to be a prognostic marker that strongly is correlated with the severity of disease. However, little is known about the potential immediate beneficial effects of acute blockade of the endothelin system in patients with symptomatic left ventricular dysfunction. We assessed the hemodynamic effects and safety of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with moderate to severe heart failure. METHODS AND RESULTS: This randomized placebo-controlled study evaluated the hemodynamic effects of 6-hour infusions of tezosentan at 5, 20, 50, and 100 mg/h compared with placebo in 61 patients with New York Heart Association class III to IV heart failure. Plasma endothelin-1 and tezosentan concentrations were also determined. Treatment with tezosentan caused a dose-dependent increase in cardiac index ranging from 24.4% to 49.9% versus 3.0% with placebo. Tezosentan also dose-dependently reduced pulmonary capillary wedge pressure and pulmonary and systemic vascular resistances, with no change in heart rate. No episodes of ventricular tachycardia or hypotension requiring drug termination were observed during tezosentan infusion. Tezosentan administration resulted in dose-related increased plasma endothelin-1 concentrations. CONCLUSIONS: The present study demonstrated that tezosentan can be safely administered to patients with moderate to severe heart failure and that by virtue of its ability to antagonize the effects of endothelin-1, it induced vasodilatory responses leading to a significant improvement in cardiac index. Further studies are under way to determine the clinical effects of tezosentan in the setting of acute heart failure.
Authors:
G Torre-Amione; J B Young; J Durand; B Bozkurt; D L Mann; I Kobrin; C M Pratt
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  103     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2001 Feb 
Date Detail:
Created Date:  2001-02-22     Completed Date:  2001-06-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  973-80     Citation Subset:  IM    
Affiliation:
Winters Center for Heart Failure Research, the Eugene and Judith Campbell Laboratories for Cardiac Transplantation Research, Houston, Texas, USA. gtorre@bcm.tmc.edu
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MeSH Terms
Descriptor/Qualifier:
Blood Pressure / drug effects
Dose-Response Relationship, Drug
Double-Blind Method
Endothelin-1 / blood
Female
Heart Failure / blood,  drug therapy*
Heart Function Tests / drug effects
Heart Rate / drug effects
Hemodynamics / drug effects*
Humans
Infusions, Intravenous
Male
Middle Aged
Pulmonary Wedge Pressure / drug effects
Pyridines / administration & dosage*,  adverse effects,  pharmacokinetics
Receptor, Endothelin A
Receptor, Endothelin B
Receptors, Endothelin / antagonists & inhibitors*
Tetrazoles / administration & dosage*,  adverse effects,  pharmacokinetics
Treatment Outcome
Vascular Resistance / drug effects
Vasodilator Agents / administration & dosage
Chemical
Reg. No./Substance:
0/Endothelin-1; 0/Pyridines; 0/Receptor, Endothelin A; 0/Receptor, Endothelin B; 0/Receptors, Endothelin; 0/Tetrazoles; 0/Vasodilator Agents; 0/tezosentan

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


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