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Clinical InvestigationsPulmonary CirculationEffects of the Dual Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Arterial Hypertension: A 1-Year Follow-up Study
Section snippets
Patient Selection
All eligible patients had participated in the preceding double-blind, placebo-controlled clinical study involving 3 to 7 months of treatment with 125 mg bid of bosentan or placebo.1920 Inclusion/exclusion criteria for the preceding study have been described previously.1920 Briefly, patients had symptomatic, severe PPH or PH associated with scleroderma in functional classes III-IV (according to the modified New York Heart Association [NYHA] classification,5 which ranks PAH severity in classes I
Results
Of the 32 patients randomized in the preceding study to receive bosentan or placebo (2:1 ratio), 3 patients from the placebo group did not participate in the open-label study due to clinical worsening of PAH (Fig 1). Of the 29 enrolled patients, 21 patients had received bosentan in the preceding study (“ex-bosentan”; 100% of the eligible bosentan-treated patients) and 8 patients had received placebo in the preceding study (“ex-placebo”; 73% of the eligible placebo-treated patients). All 29
Discussion
The present study is the first trial investigating the long-term safety and efficacy of bosentan in the treatment of PAH. In the preceding double-blind, placebo-controlled study, bosentan demonstrated favorable hemodynamic effects—including decreases in pulmonary pressures and resistances—after 3 months of treatment. These effects were accompanied by an increase in exercise capacity, an improvement in functional class, and a reduction in the incidence of clinical deterioration.1920 In this
Appendix
Olivier Sitbon, MD; David B. Badesch, MD; Richard N. Channick, MD; Adaani Frost, MD; Ivan M. Robbins, MD; Victor F. Tapson, MD; Gérald Simonneau, MD; and Lewis J. Rubin, MD, contributed to study recruitment and assessments, and to the preparation of the article. Dr. Sitbon collected long-term hemodynamic data. Frédéric Bodin, MD; Maurizio Rainizio, PhD; and Sébastien Roux, MD, designed the study, monitored the clinical and laboratory assessments, performed the study analysis, and contributed to
ACKNOWLEDGMENT
We thank all of the local investigators and their staff; Annie Pelissier from Université de Bicêtre, Bicêtre, France; Chris Stevens, Kris Wynne, Betty Booker, Karen Fagan, and Bertron Groves from University of Colorado Health Sciences Center, Denver, CO; Katie Kinninger from the Division of Pulmonary and Critical Care Medicine, University of California San Diego, CA; Helena Purl from Baylor College of Medicine and the Methodist Hospital, Houston, TX; Wendi R. Mason from Vanderbilt University
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This study was supported by Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.
The authors are consultants or investigators for Actelion Pharmaceuticals Ltd.