Improved Outcomes with Early Aggressive Therapy in Pediatric Pulmonary Hypertension.

BACKGROUND: Pediatric pulmonary arterial hypertension (PAH) carries high mortality with 81% 5-year transplant-free survival. The global Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension-2 (TOPP-2; NCT02610660) registry was created to assess the treatments and outcomes of newly diagnosed pediatric PAH patients. This study evaluates real-world treatment strategies and their relationship with outcomes. METHODS: Within TOPP-2, 445 subjects with newly diagnosed, catheterization-confirmed WSPH Group 1 pediatric PAH were enrolled. Treatment regimens were classified as none, calcium channel blocker monotherapy, PAH-targeted Monotherapy (Mono), Dual, Triple (enteral/inhaled only), or triple including parenteral prostanoid (TripleX). Baseline treatment strategy was defined as medications received three months following diagnosis. Primary clinical endpoint was death or lung transplantation. RESULTS: Dual therapy was the most common baseline treatment regimen (40.2%), followed by Monotherapy (29.0%). Phosphodiesterase type 5 inhibitors were the most common class of PAH-targeted therapy (72.4%) followed by endothelin receptor antagonists (59.3%). Adjusting for disease severity at diagnosis, baseline Dual patients had lesser hazard of death/transplant than Mono patients escalating to Dual by year one (HR=0.30, 95% CI=0.16-0.56, p<0.001). Baseline TripleX patients had lesser hazard of death/transplant than those started on enteral/inhaled therapy only and escalated to parenteral by year one (HR=0.28, 95% CI=0.15-0.50, p<0.001). DISCUSSION: A wide range of pediatric PAH initial medication strategies were observed in the TOPP-2 registry. Therapy regimen escalation within the first year, to Dual for lower-risk patients or to TripleX for higher-risk patients, was associated with worse outcomes compared to those treated more aggressively upfront, supporting upfront over sequential combination therapies.