Longer-term bosentan therapy improves functional capacity in Eisenmenger syndrome: results of the BREATHE-5 open-label extension study.
BACKGROUND
Bosentan, an oral endothelin ET(A)/ET(B) 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.
Gatzoulis
Michael A
MA
Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, London, UK. m.gatzoulis@rbh.nthames.nhs.uk
Beghetti
Maurice
M
Galiè
Nazzareno
N
Granton
John
J
Berger
Rolf M F
RM
Lauer
Andrea
A
Chiossi
Eleonora
E
Landzberg
Michael
M
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004541:Eisenmenger Complex / Q000188:drug therapy* / Q000503:physiopathology*; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan