Congenital heart diseaseEfficacy and Safety of Bosentan for Pulmonary Arterial Hypertension in Adults With Congenital Heart Disease
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.
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Gender-related differences in pulmonary arterial hypertension targeted drugs administration
2016, Pharmacological ResearchCitation Excerpt :A pooled analysis of six randomized clinical trials (Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies [ARIES]-1; ARIES-2; Bosentan: Randomized Trial of Endothelin Receptor Antagonist Therapy [BREATHE]-1; BREATHE-2; sitaxsentan To Relieve Impaired Exercise [STRIDE]-1; STRIDE-2; and STRIDE-4) including 1130 patients showed a 29.7 m greater placebo-adjusted response to ERAs of the six-minute walking distance (6MWD) in women than in men (p = 0.03) [56]. In contrast, male patients affected by congenital heart disease-associated PAH (CHD-APAH) seem to benefit more than women from bosentan administration (+33 m at the 6MWD, p < 0.01) [57]. With regards to clinical outcomes the aforementioned pooled analysis [56] showed a reduced risk of clinical events (death, lung transplant, atrial septostomy, hospitalization due to worsening PAH, withdrawal for worsening right-sided heart failure, or addition of prostacyclin analogues or phosphodiesterase inhibitors for PAH) after adjusting for study and baseline walk distance due to ERAs in women (OR: 0.27; 95% CI, 0.15–0.55) but not in men (OR:1.28; 95% CI, 0.22–7.49).
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2014, Side Effects of Drugs AnnualCitation Excerpt :No clinically relevant or statistically significant changes in liver aminotransferases were found in a prospective study of the use of bosentan in 39 adults with congenital heart disease and pulmonary arterial hypertension, 10 of whom had Down’s syndrome. There were no withdrawals because of suspected adverse reactions, of which headache (n = 10) and lower-limb edema (n = 4) were the most common [76c]. In a retrospective study of 20 patients who took bosentan for pulmonary arterial hypertension there were few adverse reactions [77c].
Long-term effect of bosentan in pulmonary hypertension associated with complex congenital heart disease
2013, Revista Portuguesa de CardiologiaCitation Excerpt :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.
Congenital Heart Disease and Pulmonary Hypertension
2012, Heart Failure ClinicsCitation Excerpt :Several studies have shown continued benefit in exercise tolerance (6MWT), NYHA functional class, and physical/mental health (Short Form-36 score), as far as 5 years from initiation of therapy. This benefit is more robust in patients with PAH-CHD without Down syndrome.118–121 The predominant adverse reaction of bosentan is increased hepatic transaminases, which can be seen up to ∼10% of patients.105,116
Evidence base for specific pulmonary vasodilators in adults with congenital heart disease
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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.