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

Abstract

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.

• Authors: Michael A Gatzoulis, Maurice Beghetti, Nazzareno Galiè, John Granton, Rolf M F Berger, Andrea Lauer, Eleonora Chiossi, Michael Landzberg, BREATHE-5 Investigators
• Journal: International journal of cardiology (Int J Cardiol) Vol. 127 Issue 1 Pg. 27-32 (Jun 23 2008) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 17658633 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Sulfonamides
• Bosentan

Topics

• Adult
• Aged
• Antihypertensive Agents (administration & dosage)
• Bosentan
• Double-Blind Method
• Drug Administration Schedule
• Eisenmenger Complex (drug therapy, physiopathology)
• Exercise Tolerance
• Female
• Humans
• Male
• Middle Aged
• Sulfonamides (administration & dosage)
• Treatment Outcome
• Vascular Resistance (drug effects)