Early Intervention, Combination Therapy Improve Outcomes in Pediatric PAH

A new report outlines helpful strategies for pediatric patients with pulmonary arterial hypertension, although experts say more research is needed to catch up with advances in the field.

Children with pulmonary arterial hypertension (PAH) benefit from aggressive prostanoid dosing in combination with other drugs targeting the condition, according to a new report.1

The study, published in the Annals of the American Thoracic Society, offers a helpful corollary to recent advances in PAH treatment in adults.

Corresponding author Johannes M. Douwes, MD, PhD, of Beatrix Children’s Hospital in the Netherlands, and colleagues wrote that to date, there had not been a significant study looking at dosing and weaning strategies for parenteral prostanoid therapy in pediatric PAH.

The investigators therefore decided to retrospectively analyze children with PAH to see how dosing and therapy choice affected transplant-free survival. They compiled a cohort of 275 children with PAH. Of those, 98 patients received intravenous or subcutaneous (IV/SC) prostanoid therapy. Most of those patients (46%) were given prostanoids along with PAH-targeted drugs as dual therapy, and 34% were given prostanoids as part of triple therapy. The remaining 20% received prostanoid monotherapy.

In most cases, prostanoid therapy began within a year of diagnosis and involved just one type of IV/SC prostanoid. Thirty patients used more than one prostanoid. The most common prostanoid administered was IV epoprostenol (92 patients). The median time-averaged dose in the study was 37 ng/kg/min, Douwes and colleagues said. Five patients were excluded from the final analysis because their prostanoid therapy lasted less than 3 months within the study period.

The investigators' analysis showed patients who had either mean pulmonary arterial pressure <35 mm HG and/or pulmonary vascular resistance index <4.4 Wood units/m2 were more likely to have favorable long-term outcomes. The authors added that the conditions of treatment also affected outcomes.

“For these children, early initiation of IV/SC prostanoid therapy, higher doses of IV/SC prostanoids, and the combination with additional PAH-targeted therapy were all independently associated with favorable outcome,” the authors said.

In an accompanying editorial,2 Lea C. Steffes, MD, of Stanford University Medical School, and Eric D. Austin, MD, MSCI, of Vanderbilt University Medical Center, said the study is important because it fills a gap in the literature.

“Although this increasingly robust adult data suggests an overall benefit from aggressive early upfront therapy with a 2 or 3 drug regimen at time of diagnosis, the optimal approach for the treatment of pediatric PAH remains unclear,” they said.

Steffes and Austin said the study was relatively large in size, although they added that it was limited because it was retrospective in nature and because in the study, prostanoid therapy was only initiated in high-risk cases or patients with insufficient responses to non-parenteral therapy.

Furthermore, in the decade since the end of the study period, they said a shift has taken place away from IV prostanoids and toward SC prostanoids, and more patients are now being treated with Potts shunts than was the case at the time of the study. No patients in the study received a Potts shunt. Steffes and Austin said the ever-changing landscape of PAH techniques underscores the importance of new and up-to-date investigations. However, they said the current study is a strong starting point.

“Given the relative paucity of evidence informing pediatric-specific dosing and therapeutic strategies in PAH, this work should serve as preliminary evidence to support future prospective studies in children with PAH,” they concluded.


  1. Douwes JM, Zijlstra WMH, Rosenzweig EB, et al. Parenteral prostanoids in pediatric pulmonary arterial hypertension: start early, dose high, combine. Ann Am Thorac Soc. 2022;19(2):227-237. doi:10.1513/AnnalsATS.202012-1563OC
  2. Steffes LC, Austin ED. Upfront combination therapy: growing the case to get ahead of pediatric pulmonary arterial hypertension. Ann Am Thorac Soc. 2022;19(2):163-165. doi:10.1513/AnnalsATS.202108-975ED