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.
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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)
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Chemical References |
- Antihypertensive Agents
- Sulfonamides
- Bosentan
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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)
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