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Published on: May 11, 2015

Improved Outcomes with Early Aggressive Therapy in Pediatric Pulmonary Hypertension

Benjamin S Frank1, Maurice Beghetti2, Rolf M F Berger3

  • 1University of Colorado, School of Medicine, Department of Pediatrics Section of Cardiology, Aurora, USA benjamin.frank@childrenscolorado.org.

The European Respiratory Journal
|August 6, 2026
PubMed

Insights

Early aggressive combination therapy for pediatric pulmonary arterial hypertension (PAH) improves survival. Upfront dual or triple therapy in pediatric PAH patients is linked to better outcomes than sequential escalation.

Area of Science:

  • Pediatric Cardiology
  • Pulmonary Hypertension Research
  • Clinical Trials and Registries

Background:

  • Pediatric pulmonary arterial hypertension (PAH) has a high mortality rate, with 5-year transplant-free survival at 81%.
  • The Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension-2 (TOPP-2) registry was established to analyze treatments and outcomes in newly diagnosed pediatric PAH patients.
  • This study specifically evaluates real-world treatment strategies and their impact on patient outcomes.

Purpose of the Study:

  • To assess the relationship between initial treatment strategies and clinical outcomes in pediatric pulmonary arterial hypertension (PAH).
  • To analyze real-world data from the TOPP-2 registry on treatment patterns and survival in pediatric PAH.
  • To compare outcomes based on different baseline medication regimens and treatment escalation approaches.

Main Methods:

  • The TOPP-2 registry enrolled 445 subjects with newly diagnosed, catheterization-confirmed World Symposium on Pulmonary Hypertension (WSPH) Group 1 pediatric PAH.
  • Treatment regimens were categorized into none, calcium channel blocker monotherapy, PAH-targeted monotherapy (Mono), dual therapy, triple therapy (enteral/inhaled only), or triple therapy including parenteral prostanoid (TripleX).
  • Baseline treatment strategy was defined as medications received three months post-diagnosis, with death or lung transplantation as the primary clinical endpoint.

Main Results:

  • Dual therapy (40.2%) and Monotherapy (29.0%) were the most common baseline treatment regimens.
  • Phosphodiesterase type 5 inhibitors (72.4%) and endothelin receptor antagonists (59.3%) were the most frequently used PAH-targeted therapies.
  • Adjusted analyses showed that patients on baseline dual therapy had a significantly lower hazard of death/transplant compared to those escalating from monotherapy (HR=0.30). Baseline TripleX patients also had a significantly lower hazard of death/transplant compared to those escalating to parenteral therapy later (HR=0.28).

Conclusions:

  • A diverse range of initial medication strategies for pediatric PAH was observed in the TOPP-2 registry.
  • Treatment escalation within the first year to dual therapy for lower-risk patients or TripleX for higher-risk patients was associated with worse outcomes.
  • These findings support the use of upfront combination therapies over sequential escalation for improved outcomes in pediatric PAH.
Abstract

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