Combination therapy with bosentan and sildenafil in Eisenmenger syndrome: a randomized, placebo-controlled, double-blinded trial.

Abstract

To evaluate the efficacy of combining the dual endothelin receptor antagonist, bosentan, and the phosfodiesterase-5-inhibitor, sildenafil, in patients with Eisenmenger syndrome. The study was a randomized, placebo-controlled, double-blinded, cross-over design. Patients with Eisenmenger syndrome (n = 21) were treated open label with bosentan for 9 months. After 3 months, sildenafil/placebo was added for 3 months, and a cross-over was performed for the last 3 months. At baseline and after 3, 6, and 9 months, patients were examined with 6 min walk test, oxygen saturations, N-terminal pro-brain natriuretic peptide, New York Heart Association (NYHA) classification, cardiac catheterization, and magnetic resonance imaging. The primary endpoint was changed in 6 min walk distance (MWD). Bosentan improved the 6 MWD (377 vs. 414 m, P = 0.001), pulmonary vascular resistance (PVR) (28 vs. 22 wood, P = 0.01), and pulmonary blood flow (2.6 vs. 3.5 L/min, P = 0.01). Adding sildenafil to bosentan did not improve the 6 MWD significantly (21 vs. 8 m, P = 0.48), but increased saturation at rest (2.9 vs. -1.8%, P < 0.01). In Eisenmenger syndrome, treatment with bosentan significantly improved walking distance, pulmonary blood flow, and PVR. Adding sildenafil to bosentan did not significantly improve walking distance but did increase saturation at rest. http://www.ClinicalTrial.gov: NCT00303004.