Sitaxsentan treatment for patients with pulmonary arterial hypertension discontinuing bosentan

J Heart Lung Transplant. 2007 Jan;26(1):63-9. doi: 10.1016/j.healun.2006.10.019.


Background: Bosentan, an oral ET(A)/ET(B) receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH). However, some patients discontinue bosentan because of hepatotoxicity or inadequate efficacy. Sitaxsentan, an oral, ET(A)-selective endothelin antagonist currently under investigation, may be an alternative treatment option. In this study we evaluate the safety and efficacy of sitaxsentan in patients discontinuing bosentan.

Methods: Forty-eight patients with idiopathic PAH or PAH associated with connective-tissue disease or congenital heart disease were randomized (double-blind) to a single daily dose of either 50 mg or 100 mg sitaxsentan. Thirty-five of the 48 patients discontinued bosentan because of inadequate efficacy, as judged by the investigator, and 13 discontinued bosentan for safety concerns. Study end-points included change in 6-minute walk distance (6MWD), change in World Health Organization (WHO) functional class, time to clinical worsening, and change in Borg dyspnea score (Borg) from baseline to Week 12.

Results: With 100 mg sitaxsentan, 5 of 15 patients (33%) who discontinued bosentan because inadequate efficacy improved, demonstrating a >15% increase in 6MWD, vs 2 of 20 patients (10%) treated with 50 mg sitaxsentan. Fifteen percent and 20% of these patients had a >15% decrease in 6MWD in the 50- and 100-mg groups, respectively. Similar results were seen for the Borg and WHO functional class. Of the 12 patients discontinuing bosentan because of hepatotoxicity, 1 developed elevated liver enzymes at 13 weeks of sitaxsentan therapy. Overall, sitaxsentan was well tolerated.

Conclusions: Sitaxsentan may represent a safe and efficacious alternative endothelin receptor antagonist for patients discontinuing bosentan.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Child
  • Double-Blind Method
  • Endothelin Receptor Antagonists*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Isoxazoles / therapeutic use*
  • Male
  • Middle Aged
  • Sulfonamides / therapeutic use*
  • Thiophenes / therapeutic use*
  • Treatment Outcome


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Isoxazoles
  • Sulfonamides
  • Thiophenes
  • sitaxsentan
  • Bosentan