Abstract 2765: Maintenance of Improvement in 6-Minute Walk Distance with Long Term Bosentan Treatment: Results of the BREATHE-1 Open-Label Extension Study
BACKGROUND: Bosentan, an oral dual endothelin receptor antagonist, is indicated for use in patients with functional class (FC) III and IV pulmonary arterial hypertension (PAH). The aim of this open-label extension (OLE) study was to provide long-term data on the efficacy and safety of bosentan.
METHODS: Eligible patients had completed the placebo-controlled, randomized BREATHE-1 study. All patients received bosentan (initial dose, 62.5 mg twice daily [bid], titrated to 125 mg bid after 4 weeks). Endpoints included 6-minute walk distance (6MWD), clinical worsening (defined as death, hospitalization or discontinuation due to worsening PAH, or epoprostenol initiation), change in FC, and adverse events.
RESULTS: Of 201 patients completing BREATHE-1, 200 entered the OLE. Patients were treated for a mean of 68.4 weeks and up to 121 weeks. Mean 6MWD for all patients improved by 33.2 m at study end from BREATHE-1 baseline, with maintenance of the 6MWD improvement observed during the placebo controlled phase (see Table 1⇓). At 48 weeks into the OLE, 77.5% of the patients had not experienced clinical worsening, and 51% of patients had an improved WHO class. After 72 weeks into the OLE, 89.6% of patients remaining in the study had not required epoprostenol therapy. Bosentan was generally well tolerated with no unexpected safety concerns. Over the course of the study 14.5% of patients discontinued due to an adverse event, 4.5% discontinued due to abnormal hepatic function.
CONCLUSION: Treatment of PAH with the dual endothelin receptor antagonist, bosentan, shows maintained efficacy for over 1 year with no unexpected safety concerns.