Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease.

Article Details

Citation

Copy to clipboard

Girgis RE, Frost AE, Hill NS, Horn EM, Langleben D, McLaughlin VV, Oudiz RJ, Robbins IM, Seibold JR, Shapiro S, Tapson VF, Barst RJ

Selective endothelin A receptor antagonism with sitaxsentan for pulmonary arterial hypertension associated with connective tissue disease.

Ann Rheum Dis. 2007 Nov;66(11):1467-72. Epub 2007 May 1.

PubMed ID

17472992 [ View in PubMed

]

Abstract

INTRODUCTION: Endothelin receptor antagonism has become an important component in the treatment of pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). The purpose of this study was to analyse the safety and effectiveness of sitaxsentan, a selective antagonist of the ET(A) receptor, in a cohort of patients with PAH and CTD. Short-term clinical and haemodynamic effects and longer-term follow-up data are presented. METHODS: A post hoc subgroup analysis was performed on 42 patients who had PAH associated with CTD, out of a group of 178 patients enrolled in a 12-week, double-blind, randomised clinical trial of sitaxsentan versus placebo. Data from 33 patients assigned to sitaxsentan 100 mg or 300 mg daily were pooled and compared with nine placebo-treated patients. There were 41 patients entered into the blinded extension study, in which all patients received either 100 mg or 300 mg sitaxsentan once daily. RESULTS: Patients treated with sitaxsentan had a mean (SD) increase in 6 minute walk distance of 20 (5) m from baseline to week 12 (p = 0.037), whereas the placebo group had a decrease of 38 (84) m, resulting in a placebo-subtracted treatment effect of 58 m (p = 0.027). Parallel improvements in quality of life and haemodynamics were also observed. No patient discontinued their drug during the 12-week trial. In the blinded extension study (median treatment duration 26 weeks), more patients were in functional class I-II than in III-IV (p<0.001) at the end of the study compared with the start of active therapy. Elevation of hepatic transaminase levels occurred in two patients. CONCLUSIONS: Sitaxsentan appears to be efficacious in patients with PAH associated with CTD.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sitaxentan	Endothelin B receptor	Protein	Humans	Unknown	Antagonist	Details
Sitaxentan	Endothelin-1 receptor	Protein	Humans	Yes	Antagonist	Details