Congenital heart disease
Efficacy and Safety of Bosentan for Pulmonary Arterial Hypertension in Adults With Congenital Heart Disease

https://doi.org/10.1016/j.amjcard.2011.07.006Get rights and content

The dual endothelin receptor antagonist, bosentan, has been shown to be well tolerated and effective in improving pulmonary arterial hypertension (PAH) symptoms in patients with Eisenmenger syndrome but data from longer-term studies are lacking. The aim of this study was to retrospectively analyze the long-term efficacy and safety of bosentan in adults with PAH secondary to congenital heart disease (PAH-CHD). Prospectively collected data from adult patients with PAH-CHD (with and without Down syndrome) initiated on bosentan from October 2007 through June 2010 were analyzed. Parameters measured before bosentan initiation (62.5 mg 2 times/day for 4 weeks titrated to 125 mg 2 times/day) and at each follow-up (1 month and 3, 6, 9, 12, 18, and 24 months) included exercise capacity (6-minute walk distance [6MWD]), pretest oxygen saturation, liver enzymes, and hemoglobin. Data were analyzed from 39 patients with PAH-CHD (10 with Down syndrome) who had received ≥1 dose of bosentan (mean duration of therapy 2.1 ± 1.5 years). A significant (p <0.0001) average improvement in 6MWD of 54 m over a 2-year period in patients with PAH-CHD without Down syndrome was observed. Men patients had a 6MWD of 33 m greater than women (p <0.01). In all patients, oxygen saturation, liver enzymes, and hemoglobin levels remained stable. There were no discontinuations from bosentan owing to adverse events. In conclusion, patients with PAH-CHD without Down syndrome gain long-term symptomatic benefits in exercise capacity after bosentan treatment. Men seem to benefit more on bosentan treatment. Bosentan appears to be well tolerated in patients with PAH-CHD with or without Down syndrome.

Section snippets

Methods

Data on all adult patients (≥18 years old, with and without Down syndrome) with PAH-CHD who were referred to and received PAH therapy at our tertiary adult congenital cardiac center were prospectively collected in a dedicated database.

Data recorded include patient demographics, underlying cardiac diagnoses, baseline medications, and hemodynamic, efficacy, and safety parameters. Before treatment initiation, all patients who give consent undergo right and left heart catheterization and

Results

The database included 39 patients with PAH-CHD, 10 of whom had Down syndrome, all having received ≥1 dose of bosentan. Three patients (1 with Down syndrome) were already on bosentan when referred to our center. Bosentan was initiated in all patients who were naive to other PAH-specific drugs, with the exception of 1 patient without Down syndrome who was already taking sildenafil 50 mg 3 times/day. In all but 2 patients bosentan was maintained as monotherapy; 1 patient was also given sildenafil

Discussion

These data provide evidence that patients without Down syndrome with PAH-CHD gain long-term symptomatic benefit in exercise capacity without detrimental effects on systemic oxygen saturation after treatment with bosentan. In addition, it provides supportive evidence that bosentan is well tolerated in patients with PAH-CHD with and without Down syndrome.

Retrospective analyses of small numbers of patients without Down syndrome with PAH-CHD (n = 6 to 17) previously naive to advanced PAH therapy

Acknowledgment

Medical writing support provided by Lisa Thomas, PhD (Elements Communications, Ltd., Westerham, Kent, United Kingdom) and statistical support by Jonathan Alsop, PhD (Numerus, Ltd., Sandhurst, Berkshire, United Kingdom) were funded by Actelion Pharmaceuticals.

References (19)

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    Patients with PAH and complex CHD are at high risk of death18 but there is a paucity of data regarding survival in such patients under vasodilator therapy. In our cohort, total mortality was 14% at four years, which is higher than in the series by Dimopoulos et al.19 (around 3% at two years), lower than that reported by Vis et al.17 (20% at four years), but similar to the recently published results by Monfredi et al.20 Differences in study design, follow-up duration and population selection may be responsible for these disparities. The safety of bosentan in this high-risk population was remarkable.

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Grant support for statistical analysis of the data and writing assistance during the development of the article was provided by Actelion Pharmaceuticals, London, United Kingdom.

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