Background: The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date.
Methods: This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score.
Results: There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mm Hg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: -35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients.
Conclusions: Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies.
Keywords: IP receptor agonist; heart failure; prostacyclin; pulmonary hypertension; pulmonary vascular disease; right ventricle.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.