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Copyright ©ERS Journals Ltd 2004
Combination therapy with bosentan and sildenafil in idiopathic pulmonary arterial hypertension
1 Dept of Respiratory Medicine, Hannover Medical School, Hannover, and 2 Dept of Cardiopulmonary Medicine, University of Leipzig, Leipzig, Germany
CORRESPONDENCE: M.M. Hoeper, Hannover Medical School, Dept of Respiratory Medicine, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Fax: 49 5115328536. E-mail: hoeper.marius@mh-hannover.de
Keywords: Bosentan, endothelin receptor antagonists, hypertension, phosphodiesterase inhibitors, pulmonary, sildenafil
Received: April 29, 2004
Accepted July 7, 2004
It has been proposed that targeted treatments should be combined for patients with idiopathic pulmonary arterial hypertension (IPAH) responding insufficiently to monotherapy.
This study followed the clinical course of nine patients with severe IPAH, in whom the endothelin receptor antagonist bosentan caused transient clinical improvement, eventually followed by a decline in exercise tolerance, who received adjunct treatment with the phospodiesterase-5-inhibitor sildenafil. Measurements included the 6-min walk distance (6MWD) and cardiopulmonary exercise testing (CPET).
The 6MWD at baseline was 346±66 m and improved to 403±80 m 3 months after introduction of bosentan treatment. However, this effect was not sustained and, after an interval of 11±5 months, the walk distance had declined to 277±80 m. At this point, sildenafil was added to bosentan. Three months later, the 6MWD had increased to 392±61 m and the patients remained stable throughout the median follow-up of 9 months (range 6–12). Measurement of the maximum oxygen uptake during CPET confirmed these results. The combination of bosentan and sildenafil was well tolerated by all patients.
These preliminary data suggest that combining bosentan and sildenafil may be safe and effective in patients with idiopathic pulmonary arterial hypertension.
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|
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