VIENNA — Preliminary reports of safety and efficacy of the selective endothelin receptor antagonist sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease have been confirmed in a double-blind study, Reda E. Girgis, M.D., reported in a poster session at the annual European congress of rheumatology.
Pulmonary arterial hypertension (PAH) related to connective tissue disease (CTD) is progressive and can be particularly problematic to manage. Prostacyclin regimens are complex and are generally reserved for critically ill patients.
One nonselective endothelin receptor antagonist, bosentan (Tracleer) is currently available but is not effective in all patients and has been associated with liver function abnormalities.
The Sitaxsentan to Relieve Impaired Exercise (STRIDE-1) study randomized 178 patients to 12 weeks of treatment with 100-mg or 300-mg sitaxsentan or placebo.
The patients had either primary pulmonary hypertension or PAH related to congenital heart disease or CTD.
A post-hoc analysis of the subgroup of 42 patients with CTD-related PAH found improvements in the results of the 6-minute walk test, New York Heart Association (NYHA) functional class, and hemodynamics.
Pooling of the 100-mg and 300-mg sitaxsentan groups found a treatment effect of 58 m on the 6-minute walk test; this was an increase of 20 m from baseline in the active treatment groups and a decrease of 38 m in the placebo group, according to Dr. Girgis of the department of medicine, Johns Hopkins University, Baltimore.
At baseline all patients were NYHA functional class II or III. By week 12, 8 of the 33 patients receiving the active treatment (24%) had improved by one NYHA functional class; none of the patients deteriorated.
In contrast, 1 of 9 (11%) placebo patients improved by one NYHA functional class and 1 of 9 (11%) deteriorated.
Among hemodynamic findings were an average increase in the cardiac index of 0.55 L/min per square meter, an average decrease in the mean pulmonary arterial pressure of 7.66 mm Hg, and an average fall in pulmonary vascular resistance of 320 dynes.sec.cm
Sitaxsentan was well tolerated. No patients experienced liver abnormalities and no patients withdrew because of adverse events.