| Exercise capacity and haemodynamics in patients with sickle cell disease with pulmonary hypertension treated with bosentan: results of the ASSET studies. | |
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MedLine Citation:
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PMID: 20175775 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Doppler-defined pulmonary hypertension (PH) in sickle cell disease (SCD) is associated with 40% mortality at 40 months. To assess the effect of bosentan in SCD-PH, two randomized, double-blind, placebo-controlled, 16-week studies were initiated. Safety concerns are particularly relevant in SCD due to comorbid conditions. ASSET-1 and -2 enrolled patients with pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PH), respectively. Haemodynamics and 6-min walk distance (6MWD) were obtained at baseline and week 16. The studies were terminated due to slow site initiation and patient enrolment (n = 26). Bosentan appeared to be well tolerated. Although sample sizes were limited, in ASSET-1 at baseline, 6MWD correlated with cardiac output (CO; P = 0.006) with non-significant inverse correlations between 6MWD and pulmonary vascular resistance (PVR; P = 0.07) and between 6MWD and right atrial pressure (P = 0.08). In ASSET-2 at baseline, there was a non-significant correlation between 6MWD and CO (P = 0.06). Due to limited sample sizes, efficacy endpoints were not analysed. However, in both studies, non-significant increases in CO were observed with bosentan compared to placebo. Similarly, non-significant decreases in PVR were observed with bosentan. Limited data in SCD-PH suggest that a low 6MWD predicts a low CO. Standard-dose bosentan appears to be well tolerated. Further investigation is warranted. Clinicaltrials.gov registration numbers NCT00310830, NCT00313196, NCT00360087. |
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Authors:
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Robyn J Barst; Kamal K Mubarak; Roberto F Machado; Kenneth I Ataga; Raymond L Benza; Oswaldo Castro; Robert Naeije; Namita Sood; Paul S Swerdlow; Mariana Hildesheim; Mark T Gladwin; |
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Publication Detail:
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Type: Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-02-17 |
Journal Detail:
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Title: British journal of haematology Volume: 149 ISSN: 1365-2141 ISO Abbreviation: Br. J. Haematol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-06-29 Revised Date: 2011-10-19 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 426-35 Citation Subset: IM |
Affiliation:
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Department of Pediatric Cardiology, Columbia University, New York, NY, USA. robyn.barst@gmail.com |
| Data Bank Information | |
Bank Name/Acc. No.:
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ClinicalTrials.gov/NCT00310830; NCT00313196; NCT00360087 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Anemia, Sickle Cell / complications*, physiopathology Antihypertensive Agents / adverse effects, therapeutic use* Double-Blind Method Exercise Test / methods Exercise Tolerance / drug effects* Female Hemodynamics / drug effects Humans Hypertension, Pulmonary / drug therapy*, etiology, physiopathology Male Middle Aged Pulmonary Artery / physiopathology Sulfonamides / adverse effects, therapeutic use* Vascular Resistance / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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Z01 CL001174-07/CL/CLC NIH HHS; ZIA HL005074-04/HL/NHLBI NIH HHS; ZIA HL005074-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Sulfonamides; 147536-97-8/bosentan |
| Investigator | |
Investigator/Affiliation:
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R J Barst / ; K K Mubarak / ; K I Ataga / ; R L Benza / ; O Castro / ; R Naeije / ; G Simonneau / ; P S Swerdlow / ; M T Gladwin / ; M Hildesheim / ; F Galacteros / ; C H U Henri Mondor / ; G Coghlan / ; K I Ataga / ; R Benza / ; A Frost / ; E Klings / ; R F Machado / ; K K Mubarak / ; L Muñoz / ; E Berman-Rosenzweig / ; W Smith / ; N Sood / ; M Telen / |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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