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.
Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, London, UK. m.gatzoulis@rbh.nthames.nhs.uk
Michael A
MA
Gatzoulis
Maurice
M
Beghetti
Nazzareno
N
Galiè
John
J
Granton
Rolf M F
RM
Berger
Andrea
A
Lauer
Eleonora
E
Chiossi
Michael
M
Landzberg
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