Sitaxentan is a highly selective enothelin-A (ETA) receptor antagonist. These receptors are found on smooth muscle cells and facilitate vasoconstriction.
The efficacy of sitaxentan has been studied in two randomised, double-blind trials, STRIDE-1 and STRIDE-2 (Sitaxentan To Relieve Impaired Exercise).
STRIDE-1 enrolled 178 patients1 with moderate to severe (WHO class II-IV) pulmonary arterial hypertension (PAH) resulting from idiopathic PAH, connective tissue disease or congenital heart disease. Patients received placebo, sitaxentan 100mg or sitaxentan 300mg once daily for 12 weeks.
After 12 weeks the sitaxentan treatment groups showed significant benefit in six-minute walk (6MW) distance, WHO functional class and haemodynamic parameters compared to the placebo group.
STRIDE-2 aimed to determine the optimal dose of sitaxentan for the treatment of PAH. The study2 enrolled 247 patients, randomised to receive placebo, sitaxentan 50mg or 100mg once daily, or open label bosentan for 18 weeks (the bosentan group was included for observation only).
At week 18, the greatest increase in 6MW distance was observed in the sitaxentan 100mg group, followed by the bosentan group, then the sitaxentan 50mg group. The sitaxentan 100mg group also showed an improved WHO functional class.
1. Langleben D, Brock T, Dixon R et al. STRIDE 1: Effects of the selective ETA receptor antagonist, sitaxsentan sodium, in a patient population with pulmonary arterial hypertension that meets tradional inclusion criteria of previous pulmonary arterial hypertension trials. J Cardiovasc Pharmacol 2004, Suppl.1: S80-84.
2. Barst R, Langleben D, Badesch D et al. Treatment of pulmonary arterial hypertension with the selective enothelin-A receptor antagonist sitaxsenstan. JACC 2006 (47): 2049-56.
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