Clinical and Hemodynamic Effects of Bosentan Dose Optimization in Symptomatic Heart Failure Patients with Severe Systolic Dysfunction, Associated with Secondary Pulmonary Hypertension – A Multi-Center Randomized Study

Abstract

Objective: Toevaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients. Method: Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8–125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb–IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use. Results: Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 ± 11.5 mm Hg , 95% confidence limit (CL) –5.4 to 5.2, p = 0.97), cardiac index shift (0.12 ± 0.45, 95% CL –0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardigraphic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs. Conclusion: In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation.

Journal

Journal ID (publisher-id): CRD

Journal ID (nlm-ta): Cardiology

Journal ID (doi): 10.1159/issn.0008-6312

Title: Cardiology

Publisher: S. Karger AG

ISSN (Print): 0008-6312

ISSN (Electronic): 1421-9751

Publication date Subscription-year: 2008

Publication date (Print): March 2008

Publication date (Electronic): 17 September 2007

Volume: 109

Issue: 4

Pages: 273-280

Affiliations

^aDepartment of Cardiology, University of Medicine and Dentistry, Newark, N.J., USA; ^bDepartment of Cardiology, Assaf Harofeh Medical Center, Zerifin, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; ^cKaplan Medical Center, Department of Cardiology Rehovot, Hebrew University Jerusalem, Jerusalem, Israel; ^dActelion Pharmaceuticals Ltd., Allschwil, Switzerland; ^eDuke Cardiology Research Center, Durham, N.C., USA; ^fWolfson Medical Center, Holon, and University of Tel Aviv, Tel Aviv, Israel; ^gDepartment of Cardiology, Barzilay Medical Center, Ashkelon, and Ben Gurion University, Beer Sheva, Israel

Article

Publisher ID: 107791 Other ID: Cardiology 2008;109:273–280

DOI: 10.1159/000107791

PubMed ID: 17873492

Copyright statement: © 2007 S. Karger AG, Basel

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Page count

Figures: 4, Tables: 3, References: 17, Pages: 8

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Categories

Subject: Original Research