Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome:: Results of the BREATHE-5 open-label extension study

Background: Bosentan, an oral endothelin ETA/ETB receptor antagonist, improves hemodynamics and exercise capacity in patients with Eisenmenger syndrome but longer-term effects are unknown. This study investigated the efficacy and safety of bosentan up to 40 weeks in these patients. Methods: Following the 16-week, double blind, placebo-controlled BREATHE-5 study of bosentan in patients with Eisenmenger syndrome, an open-label extension (OLE) was performed. Patients who completed BREATHE-5 received bosentan for an additional 24 weeks (62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.) and were analyzed in two groups; ex-placebo and ex-bosentan, according to BREATHE-5 treatment. Results: Thirty-seven patients with Eisenmenger syndrome who participated in BREATHE-5 were included in the OLE. At week 24, the 6-minute walk distance (mean +/- SE) increased from OLE baseline for the ex-placebo (+ 33.2 +/- 23.9 m) and ex-bosentan group (+ 6.7 +/- 10.0 m). The overall improvement from baseline of BREATHE-5 was + 61.3 +/- 8.1 m (95% confidence interval: [44.7, 78.0]) for the ex-bosentan group. WHO functional class was improved in both groups. Bosentan did not reduce systemic arterial blood oxygen saturation; safety profile was comparable to previous trials. Conclusions: In conclusion, these longer follow-up data support the efficacy and safety profile reported in the preceding BREATHE-5 study of bosentan treatment of Eisenmenger syndrome, challenging the notion that pulmonary vascular disease and severe functional impairment in these patients are not amenable to therapy. (C) 2007 Elsevier Ireland Ltd. All rights reserved.