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

被引:139
作者
Iversen, Kasper [1 ]
Jensen, Annette S. [1 ]
Jensen, Tim V. [2 ]
Vejlstrup, Niels G. [1 ]
Sondergaard, Lars [1 ]
机构
[1] Copenhagen Univ Hosp, Dept Cardiol, Rigshosp, Sect 2014, DK-2100 Copenhagen, Denmark
[2] Copenhagen Univ Hosp, Rigshosp, Dept Pediat, DK-2100 Copenhagen, Denmark
关键词
Congenital heart defects; Heart septal defects; Pulmonary hypertension; PULMONARY-ARTERIAL-HYPERTENSION; CONGENITAL HEART-DISEASE; RECEPTOR ANTAGONIST BOSENTAN; INHALED ILOPROST; ORAL SILDENAFIL; SEPTAL-DEFECT; NITRIC-OXIDE; TREPROSTINIL; EPOPROSTENOL; EFFICACY;
D O I
10.1093/eurheartj/ehq011
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1124 / 1131
页数:8
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