PURPOSE: Sitaxsentan, an oral, endothelin-A receptor antagonist, has been shown to improve exercise capacity and cardiopulmonary hemodynamics in patients with PAH. We evaluated the long-term effects of sitaxsentan 100 mg once daily on right-heart structure and function evaluated by echocardiogram after 28 and 52 weeks of treatment in patients with PAH.
METHODS: Twelve patients, (3 males and 9 females, mean age 46 years), World Health Organization Functional Class (WHO FC) I-III, were enrolled in an open label study. Six-minute walk distance (6MWD), WHO FC, cardiopulmonary hemodynamics and echocardiographic variables were assessed at baseline, 28 and 52 weeks of treatment with sitaxsentan. Statistical analysis used were two tailed paired t test. Values are expressed as mean ±SD.Statistical analysis used were two tailed paired t test. Values are expressed as mean ± SD.
RESULTS: Mean baseline 6MWD was 465 ±139 m, with 1 WHO FC I, 9 WHO FC II, and 2 WHO FC III patient. Mean baseline pulmonary arterial pressure was 41.4 ±9.0mmHg, pulmonary capillary wedge pressure 8.45 ±4.1mmHg, and pulmonary vascular resistance 8.43 ±4.3mmHg/L/min. Baseline echocardiographic findings were: right ventricular (RV) size 3.94 ±0.7cm, right ventricular ejection fraction (RVEF) 32.5 ±9.4%, and right ventricular systolic pressure (RVSP) 68.3 ±13.9mmHg. Sitaxsentan treatment improved 6MWD (+20.6 m at 28 weeks and +1.5 m at 52 weeks) and WHO FC. There was a significant decrease in RV size at 52 weeks (−0.53 ±0.6cm, p=0.036). RVEF significantly improved at 28 weeks (+5.42 ±7.5%, p=0.03) and at 52 weeks (8.33 ±9.7%, p=0.033). RVSP improved, but was not statistically significant, at 28 weeks or 52 weeks.
CONCLUSION: In a small cohort of patients with mild-moderate PAH, treatment with sitaxsentan 100 mg once daily, for up to 52 weeks, improved exercise capacity and demonstrated significant improvements in RV size and increase in RVEF, by at least 25% from baseline after one year of therapy.
CLINICAL IMPLICATIONS: Patients with mild-moderate PAH, impaired exercise capacity, increased RV size, and RVEF may benefit treatment with sitaxsentan 100 mg once daily.
DISCLOSURE: Dianne Zwicke, Consultant fee, speaker bureau, advisory committee, etc. Dr. Zwicke has received consultant fees in the past from Encysive; Product/procedure/technique that is considered research and is NOT yet approved for any purpose, Sitaxsentan.