Combination therapy with ambrisentan and tadalafil is well-tolerated and has an acceptable safety profile in children with pulmonary arterial hypertension (PAH) who were treatment-naive or were treated with monotherapy, according to a new study published in Pediatric Pulmonology.

“Based on these early data, further study of combination therapy in pediatric [pulmonary hypertension] is warranted,” the authors said. They also found that combination therapy is associated with improved exercise capacity and hemodynamics.

The pathophysiology and clinical symptoms of PAH are similar between children and adults, so children with the disease are often treated based on strategies extrapolated from adult studies. 

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For example, the combination therapy of ambrisentan and tadalafil have been shown in a clinical trial in adult patients with PAH to reduce the occurrence of clinical failure events defined as death, hospitalization for worsening PAH, disease progression, or unsatisfactory long-term clinical response. However, this approach has not been tested in children.

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Here, researchers reported safety and tolerability data of ambrisentan plus tadalafil treatment in children with PAH. A total of 43 children, aged 4 to 17.5 years with pulmonary hypertension groups 1, 3, and 5 received the combination therapy. The results showed that there were significant improvements in change scores at follow-up.

Moreover, patients who either received no therapy or monotherapy with a phosphodiesterase 5 inhibitor or endothelin receptor antagonist before the start of the combination therapy also showed significant improvements in their 6-Minute Walk Distance scores, mean pulmonary artery pressures, pulmonary vascular resistance measures, and plasma N-terminal pro b-type natriuretic peptides.

The severity of the disease improved in 39.5% of patients and remained unchanged in 53.5% of them. Furthermore, pulmonary hypertension risk scores improved in 16% of patients and remained unchanged in 56% of them, while it declined in 14% of them.

Only 3 patients discontinued therapy and 7 were hospitalized due to worsening disease. No deaths or lung transplantations occurred.


Issapour A, Frank B, Crook S, et al. Safety and tolerability of combination therapy with ambrisentan and tadalafil for the treatment of pulmonary arterial hypertension in children: real-world experience. Pediatr Pulmonol. Published online December 17, 2021. doi:10.1002/ppul.25796