Study objectives: We report on the long-term safety and efficacy of bosentan treatment in patients with pulmonary arterial hypertension (PAH).
Background: In a preceding study, bosentan was well tolerated and significantly improved the exercise capacity and hemodynamics of patients with PAH after 12 weeks of treatment.
Design: The present study was an open-label extension to the preceding double-blind, placebo-controlled study of 32 patients with PAH (primary or associated with scleroderma) who received bosentan or placebo at 125 mg bid for 3 to 7 months.
Patients: Twenty-nine of the original 32 patients received bosentan for an additional year (62.5 mg bid for 4 weeks and then 125 mg bid).
Interventions: Study end points included long-term safety, 6-min walk distance at week 4, modified New York Heart Association (NYHA) functional class of PAH at month 12, and the occurrence of withdrawal due to clinical worsening. Additional exploratory analyses included a walk test at month 6 for 19 patients and hemodynamic assessment at month 12 for 11 patients.
Results: At month 6, assessed patients continuing bosentan treatment maintained the improvement in walk distance observed at the end of the previous study (mean +/- SEM, 60 +/- 11 m), and patients starting bosentan treatment improved their walk distance by 45 +/- 13 m. Long-term treatment with bosentan for > 1 year was associated with an improvement in hemodynamic parameters and modified NYHA functional class. Overall, bosentan treatment was well tolerated. No patient underwent transplantation or died.
Conclusions: Long-term treatment with bosentan is safe and has sustained benefits on exercise capacity and hemodynamics in patients with PAH.