Key result
Sitaxsentan at doses of 100 and 300 mg/day improved exercise capacity, NYHA functional class, cardiac index, and pulmonary vascular resistance in patients with pulmonary arterial hypertension.
Why the study?
Does sitaxsentan improve exercise capacity and hemodynamics in patients with pulmonary arterial hypertension?
Does sitaxsentan improve exercise capacity and hemodynamics in patients with pulmonary arterial hypertension?
Sitaxsentan, a selective ET(A) receptor antagonist, improves exercise capacity and hemodynamics in patients with PAH, with the 100 mg/day dose offering a better safety profile than higher doses.
Answers are grounded in this paper and cite their sources.
Supports selective ET(A) antagonism in PAH; leaves open durability, safety, and need for randomized confirmation.
Sitaxsentan, a highly selective endothelin-A (ET(A)) receptor antagonist (6500-fold more selective for ET(A) receptors than endothelin-B (ET(B)) receptors), may benefit patients with pulmonary artery hypertension (PAH) by blocking the vasoconstrictor effects of ET(A) receptors while maintaining the vasodilator/clearance functions of ET(B) receptors. In its first randomised, placebo-controlled study, Sitaxsentan to Relieve Impaired Exercise-1 (STRIDE-1), sitaxsentan improved exercise capacity assessed by 6 min walk, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association class II, III and IV patients with idiopathic PAH, PAH related to connective tissue disease or PAH related to congenital heart disease. In STRIDE-1, doses of 100 and 300 mg/day p.o. were evaluated. Although both doses showed equivalent efficacy, the lower dose had a more tolerable safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg/day doses, both in de novo patients and in patients previously treated with the ET(A)/ET(B) receptor antagonist bosentan. Long-term comparative studies are necessary to determine whether there is a clinically meaningful difference between selective ET(A) receptor antagonism and ET(A)/ET(B) receptor antagonism.
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Horn et al. (2004) conducted a review in Pulmonary arterial hypertension. Sitaxsentan vs. Placebo was evaluated on Exercise capacity assessed by 6 min walk, New York Heart Association functional class, cardiac index and pulmonary vascular resistance. Sitaxsentan at doses of 100 and 300 mg/day improved exercise capacity, NYHA functional class, cardiac index, and pulmonary vascular resistance in patients with pulmonary arterial hypertension.
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