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Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension

Clinical experience with bosentan and sitaxentan in connective tissue disease-associated... Objectives. To report outcomes in patients with CTD-pulmonary arterial hypertension (CTD-PAH) in an observational cohort treated with bosentan or sitaxentan and determine whether differences would justify a randomized, controlled multicentre study in this subpopulation.Methods. Patients with CTD-PAH, diagnosed by right-heart catheter studies, were assigned to either bosentan or sitaxentan based on physician choice. All patients were followed up with repeat assessments and data were collected for the local registry database.Results. The bosentan- (n32) and sitaxentan- (n22) treated groups had comparable haemodynamic and prognostic measures at baseline. Repeat haemodynamic assessments showed reductions in pulmonary vascular resistance with bosentan (99dynes/s/cm5, P<0.01) and sitaxentan (92dynes/s/cm5, P<0.05). The 6-min walk distance improved at 3 months with sitaxentan (25m, P<0.05). N-terminal pro-B-type natriuretic peptide levels fell in the bosentan cohort at 6 months (70 pmol/l, P<0.05) and 1 year (83pmol/l, P<0.01). Haemoglobin fell with both drugs (at 3 months 0.5g/dl bosentan, P<0.05 and 0.9g/dl sitaxentan, P<0.005). Calculations of the difference in treatment effect did not demonstrate superiority of either therapy. The 1-year estimated clinical worsening event rates were high: 41 sitaxentan, 62 bosentan (P0.142), with serious event rates of 27 and 14 (P0.263, log-rank test), respectively. Six patients discontinued bosentan because of transaminase elevation within the first year. Estimated 1-year survival was similar in both groups and 96 overall.Conclusion. Both sitaxentan and bosentan appear effective in CTD-PAH, but the apparent additional benefit of sitaxentan reported from the open-label Sitaxentan To Relieve ImpaireD Exercise-2X study was not confirmed in this observational cohort. Although survival has improved, event rates continue to be substantial and CTD-PAH remains a therapeutic challenge. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Rheumatology Oxford University Press

Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension

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References (22)

Publisher
Oxford University Press
Copyright
The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
ISSN
1462-0324
eISSN
1462-0332
DOI
10.1093/rheumatology/keq241
pmid
20675359
Publisher site
See Article on Publisher Site

Abstract

Objectives. To report outcomes in patients with CTD-pulmonary arterial hypertension (CTD-PAH) in an observational cohort treated with bosentan or sitaxentan and determine whether differences would justify a randomized, controlled multicentre study in this subpopulation.Methods. Patients with CTD-PAH, diagnosed by right-heart catheter studies, were assigned to either bosentan or sitaxentan based on physician choice. All patients were followed up with repeat assessments and data were collected for the local registry database.Results. The bosentan- (n32) and sitaxentan- (n22) treated groups had comparable haemodynamic and prognostic measures at baseline. Repeat haemodynamic assessments showed reductions in pulmonary vascular resistance with bosentan (99dynes/s/cm5, P<0.01) and sitaxentan (92dynes/s/cm5, P<0.05). The 6-min walk distance improved at 3 months with sitaxentan (25m, P<0.05). N-terminal pro-B-type natriuretic peptide levels fell in the bosentan cohort at 6 months (70 pmol/l, P<0.05) and 1 year (83pmol/l, P<0.01). Haemoglobin fell with both drugs (at 3 months 0.5g/dl bosentan, P<0.05 and 0.9g/dl sitaxentan, P<0.005). Calculations of the difference in treatment effect did not demonstrate superiority of either therapy. The 1-year estimated clinical worsening event rates were high: 41 sitaxentan, 62 bosentan (P0.142), with serious event rates of 27 and 14 (P0.263, log-rank test), respectively. Six patients discontinued bosentan because of transaminase elevation within the first year. Estimated 1-year survival was similar in both groups and 96 overall.Conclusion. Both sitaxentan and bosentan appear effective in CTD-PAH, but the apparent additional benefit of sitaxentan reported from the open-label Sitaxentan To Relieve ImpaireD Exercise-2X study was not confirmed in this observational cohort. Although survival has improved, event rates continue to be substantial and CTD-PAH remains a therapeutic challenge.

Journal

Rheumatology – Oxford University Press

Published: Nov 30, 2010

Keywords: Pulmonary hypertension Pulmonary circulation Endothelin receptors Endothelin-1 Bosentan Sitaxentan Systemic sclerosis Connective tissue disease Drugs

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