Document Detail


Safety and tolerability of bosentan in adults with Eisenmenger physiology.
MedLine Citation:
PMID:  15676179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bosentan, a dual-endothelin receptor antagonist, is an established treatment for pulmonary arterial hypertension. We hypothesized that bosentan is safe and well tolerated in patients with Eisenmenger physiology. METHODS: In this pilot open-label study, we primarily examined safety and tolerability of oral bosentan. Patients were recruited from our adult congenital heart clinic following informed consent. Baseline and 3-month assessment included WHO functional class, resting oxygen saturations, 6-min walk test, transthoracic echocardiography and respiratory mass spectrometry. Patient clinical status and liver enzymes were closely monitored throughout. RESULTS: All 10 study patients (42+/-4 years; eight female) tolerated bosentan well. No major adverse events or significant liver enzyme elevations were observed. All but one patient felt better; none felt worse. Four patients experienced transient leg oedema. Resting oxygen saturations (83+/-5 versus 80+/-5%; P=0.011) and the distance travelled in the 6-min walk test (348+/-112 versus 249+/-117 m; P=0.004) increased relative to baseline. Changes in echocardiographic parameters (maximum aortic forward flow velocity 1.3+/-0.1 versus 1.1+/-0.2 ms, P=0.013; pulmonary arterial acceleration time 66+/-10 versus 58+/-12 m/s, P=0.02) and pulmonary blood flow (3.45+/-1.2 versus 2.58+/-1.0 L/min, P=0.008) suggested improved pulmonary haemodynamics by study end. Other echocardiographic changes suggested improved right ventricular systolic function (septal amplitude 1.0 versus 1.1 cm, P=0.048; systolic tissue Doppler velocity 4.8 versus 2.3 cm s(-1), P=0.002) by study end. CONCLUSIONS: Bosentan was safe and well tolerated in adults with Eisenmenger physiology both at initiation and after 3 months of oral therapy. Clinical status of patients and pulmonary haemodynamics appeared to improve, and this warrants further investigation.
Authors:
Michael A Gatzoulis; Paula Rogers; Wei Li; Carl Harries; Derek Cramer; Simon Ward; Ghada W Mikhail; J Simon R Gibbs
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cardiology     Volume:  98     ISSN:  0167-5273     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-28     Completed Date:  2006-08-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  147-51     Citation Subset:  IM    
Affiliation:
Adult Congenital Heart Program, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, UK. m.gatzoulis@rbh.nthames.nhs.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Antihypertensive Agents / adverse effects,  therapeutic use*
Blood Flow Velocity / drug effects
Blood Pressure / drug effects
Eisenmenger Complex / drug therapy*,  physiopathology*
Exercise Tolerance / drug effects
Female
Forced Expiratory Volume / drug effects
Heart Rate / drug effects
Humans
London
Male
Middle Aged
Oxygen Consumption / drug effects
Pilot Projects
Pulmonary Circulation / drug effects
Sulfonamides / adverse effects,  therapeutic use*
Systole / drug effects
Treatment Outcome
Ventricular Function, Right / drug effects
Vital Capacity / drug effects
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Sulfonamides; 147536-97-8/bosentan

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


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