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.