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.
OBJECTIVE
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).


METHODS
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).


METHODS
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.


METHODS
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.


CONCLUSIONS
Long-term selective ET-A blockade with sitaxsentan sodium is safe and may improve exercise capacity, functional class, and hemodynamics in patients with PAH.
Center for Pulmonary Vascular Disease, Room E-258, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote Ste Catherine, Montreal, Quebec, Canada H3T 1E2. david.langleben@mcgill.ca
David
D
Langleben
Andrew M
AM
Hirsch
Eileen
E
Shalit
Lyda
L
Lesenko
Robyn J
RJ
Barst
D000328:Adult; D065128:Endothelin Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013876:Thiophenes / Q000627:therapeutic use*
D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D013876:Thiophenes; C106276:sitaxsentan