Safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension

The aim of this single-centre retrospective observational study was to evaluate the safety, tolerability, and efficacy of an in-class combination therapy switch from bosentan plus sildenafil to ambrisentan plus tadalafil in children with pulmonary arterial hypertension. Children aged over 5 years who were established on sildenafil plus bosentan were offered to undergo a therapy switch from May 2014 to May 2021 and, if remaining in the service, followed up to May 2024. Children with Eisenmenger syndrome, open intra or extra-cardiac shunt, or with pulmonary hypertension-associated lung disease were excluded. As part of a structured clinical program children were assessed via walk test, echocardiography, cardiac magnetic resonance imaging (CMRI), cardiopulmonary exercise testing, and serum biomarkers. Fifty-two children were included, 33 in the switch group and 19 in the control group. Clinical characteristics at diagnosis and baseline assessments did not differ between groups. All children tolerated the medication switch. Over a median 13.0 [12.0,13.7] week follow-up in the switch group there was a significant improvement in World Health Organization functional class (WHO FC, p < 0.001); reduction in estimated right ventricular systolic pressure by echocardiography of 7 mmHg (p = 0.03) and a 2% increase (p = 0.03) in right ventricular ejection fraction on CMRI. There was a sustained improvement in WHO FC (p < 0.01) in the switch group at medium-term follow-up of 40.9 [35.2,49.3] weeks. Long-term outcome of transplant- or Potts shunt-free survival was comparable between the two groups.