Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease

Redo E. Girgis, Adaani E. Frost, Nicholas S. Hill, Evelyn M. Horn, David Langleben, Vallerie V. McLaughlin, Ronald J. Oudiz, Ivan M. Robbins, James R. Seibold, Shelley Shapiro, Victor F. Tapson, Robyn J. Barst

Research output: Contribution to journalArticle

Abstract

Introduction: Endothelin receptor antagonism has become an important component in the treatment of pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). The purpose of this study was to analyse the safety and effectiveness of sitaxsentan, a selective antagonist of the ETA receptor, in a cohort of patients with PAH and CTD. Short-term clinical and haemodynamic effects and longer-term follow-up data are presented. Methods: A post hoc subgroup analysis was performed on 42 patients who had PAH associated with CTD, out of a group of 178 patients enrolled in a 12-week, double-blind, randomised clinical trial of sitaxsentan versus placebo. Data from 33 patients assigned to sitaxsentan 100 mg or 300 mg daily were pooled and compared with nine placebo-treated patients. There were 41 patients entered into the blinded extension study, in which all patients received either 100 mg or 300 mg sitaxsentan once daily. Results: Patients treated with sitaxsentan had a mean (SD) increase in 6 minute walk distance of 20 (5) m from baseline to week 12 (p = 0.037), whereas the placebo group had a decrease of 38 (84) m, resulting in a placebo-subtracted treatment effect of 58 m (p = 0.027). Parallel improvements in quality of life and haemodynamics were also observed. No patient discontinued their drug during the 12-week trial. In the blinded extension study (median treatment duration 26 weeks), more patients were in functional class I-II than in III-IV (p

Original languageEnglish (US)
Pages (from-to)1467-1472
Number of pages6
JournalAnnals of the Rheumatic Diseases
Volume66
Issue number11
DOIs
StatePublished - Nov 2007

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Connective Tissue Diseases
Pulmonary Hypertension
Tissue
Hemodynamics
Placebos
Endothelin Receptors
sitaxsentan
Pharmaceutical Preparations
Therapeutics
Randomized Controlled Trials
Quality of Life
Safety

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

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Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. / Girgis, Redo E.; Frost, Adaani E.; Hill, Nicholas S.; Horn, Evelyn M.; Langleben, David; McLaughlin, Vallerie V.; Oudiz, Ronald J.; Robbins, Ivan M.; Seibold, James R.; Shapiro, Shelley; Tapson, Victor F.; Barst, Robyn J.

In: Annals of the Rheumatic Diseases, Vol. 66, No. 11, 11.2007, p. 1467-1472.

Research output: Contribution to journalArticle

Girgis, RE, Frost, AE, Hill, NS, Horn, EM, Langleben, D, McLaughlin, VV, Oudiz, RJ, Robbins, IM, Seibold, JR, Shapiro, S, Tapson, VF & Barst, RJ 2007, 'Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease', Annals of the Rheumatic Diseases, vol. 66, no. 11, pp. 1467-1472. https://doi.org/10.1136/ard.2007.069609
Girgis, Redo E. ; Frost, Adaani E. ; Hill, Nicholas S. ; Horn, Evelyn M. ; Langleben, David ; McLaughlin, Vallerie V. ; Oudiz, Ronald J. ; Robbins, Ivan M. ; Seibold, James R. ; Shapiro, Shelley ; Tapson, Victor F. ; Barst, Robyn J. / Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease. In: Annals of the Rheumatic Diseases. 2007 ; Vol. 66, No. 11. pp. 1467-1472.
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AU - Girgis, Redo E.

AU - Frost, Adaani E.

AU - Hill, Nicholas S.

AU - Horn, Evelyn M.

AU - Langleben, David

AU - McLaughlin, Vallerie V.

AU - Oudiz, Ronald J.

AU - Robbins, Ivan M.

AU - Seibold, James R.

AU - Shapiro, Shelley

AU - Tapson, Victor F.

AU - Barst, Robyn J.

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