Endothelin receptor antagonists in pulmonary arterial hypertension
Richard N. Channick, MD*,*,
Olivier Sitbon, MD ,
Robyn J. Barst, MD ,
Alessandra Manes, MD and
Lewis J. Rubin, MD*
* Pulmonary and Critical Care Division, University of California, San Diego, California, USA
Division of Pulmonary and Critical Care Medicine, University of Paris-Sud, Paris, France
Division of Pediatric Cardiology, Columbia–Presbyterian Hospital, New York, New York, USA
Institute of Cardiology, University of Bologna, Bologna, Italy
Manuscript received January 13, 2004;
accepted February 3, 2004.
*
Reprint requests and correspondence: Dr. Richard N. Channick, UCSD Medical Center, 9300 Campus Point Drive, La Jolla, California 92037, USA.
rchannick{at}ucsd.edu
Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.
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Abbreviations and Acronyms
| | CTEPH | = chronic thromboembolic pulmonary hypertension | | ERAs | = endothelin receptor antagonists | | ET | = endothelin | | ETA
| = endothelin receptor A | | ETB
| = endothelin receptor B | | IPAH | = idiopathic pulmonary arterial hypertension | | 6MWT | = 6-min walk test | | PAH | = pulmonary arterial hypertension | | WHO | = World Health Organization | | NYHA | = New York Heart Association |
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|
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|
|
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|
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|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
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|
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|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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130(5):
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|
|
|
|
|
|
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|
|
|
|
|
|
|
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127(5):
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|
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