INTERNATIONAL JOURNAL OF CARDIOLOGY | 卷:172 |
Long-term results from the EARLY study of bosentan in WHO functional class II pulmonary arterial hypertension patients | |
Article | |
Simonneau, Gerald1  Galie, Nazzareno2  Jansa, Pavel3  Bohns Meyer, Gisela Martina4  Al-Hiti, Hikmet5  Kusic-Pajic, Andjela6  Lemarie, Jean-Christophe7  Hoeper, Marius M.8  Rubin, Lewis J.9  | |
[1] Univ Paris 11, Hop Univ Bicetre, Serv Pneumol, Le Kremlin Bicetre, France | |
[2] Univ Bologna, Inst Cardiol, Bologna, Italy | |
[3] Charles Univ Prague, Fac Med 1, Dept Med 2, Clin Dept Cardiol & Angiol, Prague, Czech Republic | |
[4] Complexo Hosp Sta Casa Porto Alegre, Porto Alegre, RS, Brazil | |
[5] Inst Clin & Expt Med IKEM, Dept Cardiol, Prague, Czech Republic | |
[6] Actel Pharmaceut Ltd, Clin Dev, Allschwil, Switzerland | |
[7] Effi Stat, Paris, France | |
[8] Hannover Med Sch, Dept Resp Med, Hannover, Germany | |
[9] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA | |
关键词: Endothelin; Pulmonary arterial hypertension; Risk factors; Survival; Bosentan; | |
DOI : 10.1016/j.ijcard.2013.12.179 | |
来源: Elsevier | |
【 摘 要 】
Background: The double-blind phase of the EARLY study of bosentan remains the only randomized controlled trial of a PAH-targeted therapy in World Health Organization functional class (FC) II patients. We report on the efficacy, safety, disease worsening, survival and prognostic factors inmildly symptomatic pulmonary arterial hypertension (PAH) patients treated with bosentan in the open-label extension phase of the EARLY study. Methods: Exploratory efficacy outcomes included 6-minute walk distance (6MWD) and WHO FC. Adverse events were recorded. Kaplan-Meier analysis was used to estimate time to first PAH worsening event (death, initiation of intravenous or subcutaneous prostanoids, atrial septostomy or lung transplantation) and survival. Cox regression analysis determined factors prognostic of survival. Results: Median exposure to bosentan (n = 173) was 51 months. At the end of the bosentan-treatment assessment period, 77.8% of patients were in WHO FC I/II. Adverse events led to discontinuation of bosentan in 20.2% of patients. Aminotransferase elevations >3x upper limit of normal occurred in 16.8%. Four-year PAH-event-free survival and survival were 79.5% (95% confidence intervals [95% CI] 73.4, 85.6) and 84.8% [95% CI 79.4, 90.2], respectively. Low 6MWD, low mixed venous oxygenation, high N-terminal pro hormone of brain natriuretic peptide levels and PAH associated with connective tissue disease were associated with a higher risk of death. Conclusions: The majority of patients exposed to long-term bosentan maintained or improved their functional class. Approximately 20% of the patients discontinued treatment because of adverse events, which were most commonly PAH worsening and elevated liver enzymes. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.
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