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Comparable Efficacy of Bosentan in Eisenmenger’s Syndrome Patients with Atrial Septal Defects and Ventricular Septal Defects

R. M. F. Berger


Maurice Beghetti


Nazzareno Galiè


Michael Gatzoulis

A. Lauer

E. Chiossi

Michael Landzberg

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Conference: 2008 International PHA Conference and Scientific Sessions

Release Date: 06.20.2008

Presentation Type: Abstracts

Berger R.M.F.1, Beghetti M.2, Galiè N.3, Gatzoulis M.A.4, Granton J.5, Lauer A.6, Chiossi E.6, Landzberg M.7

1. University of Groningen, the Netherlands
2. Hôpital des Enfants, Genéve, Switzerland
3. University of Bologna, Italy
4. Royal Brompton Hospital, UK
5. Toronto General Hospital, Canada
6. Actelion Pharmaceuticals Ltd, Switzerland
7. Children’s Hospital, Boston MA, USA

BACKGROUND: Eisenmenger’s syndrome (ES) patients with atrial septal defects (ASD) differ substantially in the evolution of their pulmonary vascular disease, the ventricular loading conditions and natural course compared to those with ventricular septal defects (VSD).

Speculation has therefore arisen that response to bosentan, a dual endothelin (ETA/ETB) receptor antagonist, may vary between these patient groups. The effect on hemodynamic parameters may be more pronounced in ASD than in VSD patients, and similar to that observed in patients with idiopathic pulmonary arterial hypertension. In BREATHE-5, a placebo-controlled study in ES patients, both ASD and VSD patients were enrolled; bosentan improved hemodynamics and exercise capacity with no adverse effect on oxygen saturation (SpO2). The purpose of this subgroup exploratory analysis was to assess the relative treatment effects between the ASD and VSD group.

METHODS: ES patients with ASDs ≥ 2 cm in diameter and VSDs ≥1 cm, and hypoxia (SpO2 between 70–90%) were enrolled in this 16-week study. Methods have been previously described [Galiè N et al., Circulation 2006; 114: 48–54].

RESULTS: Five ASD patients were randomized to placebo, 8 to bosentan. Twelve patients with a VSD or both ASD and VSD (VSD/ASD+VSD) were randomized to placebo, 29 to bosentan. Results are shown in Table 1.

Table: Placebo-corrected bosentan treatment effect after 16 weeks.

Sub-group

Mean change in pulmonary vascular resistance index (PVRi), dyn·sec·cm-5 
(95% CI)

Mean change in mean pulmonary artery pressure (mPAP), mmHg (95% CI)

Mean change in 6-minute walk distance (6MWD), m (95% CI)

Mean change in systemic pulse oximetry (SpO2), % (95% CI)

ASD

–542.0 
(–1434.4, 350.3)

–11.2 
(–24.0, 1.6)

89.7 
(–32.3, 211.8)

2.3 
(–2.6, 7.2)

VSD/ ASD+ VSD

–412.3 
(–946.4, 121.9) 

–3.6 
(–9.4, 2.2) 

35.3 
(1.0, 69.5)

0.7 
(–1.2, 2.6)

Patients in both ASD and VSD/ASD+VSD subgroups showed a positive trend in hemodynamics without desaturation, as well as in the 6MWD. Improvements were of similar magnitude as in the primary analysis.

CONCLUSION: These subgroup analyses results indicate that bosentan appears to be effective in both ASD and VSD/ASD+VSD patient subgroups. Even if the data show a trend to a larger treatment effect in ASD patients no firm conclusions can be drawn given the exploratory nature of this analysis.