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.