Sustained symptomatic, functional, and hemodynamic benefit with the selective endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary arterial hypertension: a 1-year follow-up study

Chest. 2004 Oct;126(4):1377-81. doi: 10.1378/chest.126.4.1377.


Study objectives: To examine the long-term efficacy and safety of the selective endothelin-A receptor (ET-A) antagonist, sitaxsentan sodium, after 1 year of therapy in patients with pulmonary arterial hypertension (PAH).

Design: The study was a Canadian, open-label extension of at least 1-year total of active therapy (sitaxsentan, 100 mg/d), following a preceding, blinded, 12-week placebo controlled trial of sitaxsentan (placebo, or sitaxsentan, 100 mg/d or 300 mg/d), which had then been followed by a blinded active-therapy continuation study (sitaxsentan, 100 mg/d or 300 mg/d).

Patients: Eleven patients with PAH were enrolled. The condition of one patient worsened at 7 months of therapy, and the patient transferred to epoprostenol therapy. The remaining 10 patients (idiopathic [n = 3], connective tissue disease [n = 3], congenital heart disease [n = 4]) completed the evaluation after 1 year of active therapy.

Interventions: The end points of the study included the 6-min walk test, World Health Organization (WHO) functional class, and cardiopulmonary hemodynamic parameters.

Results: After 1 year of sitaxsentan therapy, there were significant improvements in 6-min walk distance (50-m treatment effect), WHO functional class, and hemodynamics, as compared to baseline. There were no serious adverse events, and no instances of hepatotoxicity or bleeding.

Conclusion: Long-term selective ET-A blockade with sitaxsentan sodium is safe and may improve exercise capacity, functional class, and hemodynamics in patients with PAH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Endothelin Receptor Antagonists*
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Isoxazoles / therapeutic use*
  • Male
  • Middle Aged
  • Thiophenes / therapeutic use*


  • Endothelin Receptor Antagonists
  • Isoxazoles
  • Thiophenes
  • sitaxsentan