Article Text

Download PDFPDF
Selective endothelinA receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease
  1. Reda E Girgis1,
  2. Adaani E Frost2,
  3. Nicholas S Hill3,
  4. Evelyn M Horn4,
  5. David Langleben5,
  6. Vallerie V McLaughlin6,
  7. Ronald J Oudiz7,
  8. Ivan M Robbins8,
  9. James R Seibold6,
  10. Shelley Shapiro9,
  11. Victor F Tapson10,
  12. Robyn J Barst11
  1. 1
    Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA
  2. 2
    Baylor College of Medicine and the Methodist Hospital, Houston, Texas, USA
  3. 3
    Tufts New England Medical Center, Boston, Massachusetts, USA
  4. 4
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
  5. 5
    Sir Mortimer B Davis Jewish General Hospital, Montreal, Canada
  6. 6
    University of Michigan Health System, Ann Arbor, Michigan, USA
  7. 7
    Harbor-UCLA Medical Center, UCLA Geffen School of Medicine, Torrance, California, USA
  8. 8
    Vanderbilt University Medical Center, Nashville, Tennessee, USA
  9. 9
    VA Greater Los Angeles Healthcare System, UCLA Geffen School of Medicine, Los Angeles, California, USA
  10. 10
    Duke University Medical Center, Durham, North Carolina, USA
  11. 11
    Department of Pediatric Cardiology, Columbia University College of Physicians and Surgeons, New York, USA
  1. Robyn J Barst, MD, 3959 Broadway, BHN 2-255, New York, NY 10032 USA; rjb3{at}


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<0.001) at the end of the study compared with the start of active therapy. Elevation of hepatic transaminase levels occurred in two patients.

Conclusions: Sitaxsentan appears to be efficacious in patients with PAH associated with CTD.

  • endothelin
  • exercise capacity
  • hemodynamics
  • pulmonary hypertension
  • scleroderma

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Financial disclosure: Supported by Encysive Pharmaceuticals (Houston, Texas, USA).

  • Abbreviations:
    6-minute walk distance
    Cardiac Index
    connective tissue disease
    endothelin receptor isoform type A
    endothelin receptor isoform type B
    idiopathic pulmonary arterial hypertension
    mixed connective tissue disease
    mean pulmonary artery pressure
    mean right atrial pressure
    nitric oxide
    New York Heart Association
    pulmonary arterial hypertension
    mean pulmonary capillary wedge pressure
    pulmonary vascular resistance
    Short Form 36
    systemic lupus erythematosus
    systemic sclerosis
    Sitaxsentan to Relieve Impaired Exercise trial
    Sitaxsentan to Relieve Impaired Exercise extension trial
    upper limit of the normal range