Parenteral Prostanoids in Pediatric Pulmonary Arterial Hypertension: Start Early, Dose High, Combine

RATIONALE: There is currently no data supporting specific dosing and weaning strategies for parental prostanoid therapy in children with pulmonary arterial hypertension (PAH).

OBJECTIVES: To describe the clinical practice of intravenous (IV) or subcutaneous (SC) prostanoid therapy in pediatric PAH and identify dosing strategies associated with favorable outcome.

METHODS: From an international multicenter cohort of 275 children with PAH, 98 patients that received IV/SC prostanoid therapy were retrospectively analyzed.

RESULTS: IV/SC prostanoids were given as monotherapy (20%), or combined with other PAH-targeted drugs as dual (46%) or triple therapy (34%). The median time-averaged dose was 37 ng/kg/min, ranging 2-136 ng/kg/min. During follow up, IV/SC prostanoids were discontinued and transitioned to oral or inhaled PAH-targeted therapies in 29 patients. Time-dependent ROC analyses showed specific hemodynamic criteria at discontinuation of IV/SC prostanoids (mean pulmonary arterial pressure (mPAP)<35 mmHg and/or pulmonary vascular resistance index (PVRi)<4.4 WU.m2) identified children with favorable long-term outcome after IV/SC prostanoid discontinuation, compared to patients that do not meet those criteria (P=0.027). In the children that continued IV/SC prostanoids until end of follow-up, higher dose (at least >25 ng/kg/min), early start after diagnosis and combination with other PAH-targeted drugs were associated with better transplant-free survival.

CONCLUSIONS: Early initiation of IV/SC prostanoids, higher doses of IV/SC prostanoids and combination with additional PAH-targeted therapy were associated with favorable outcome. Transition from IV/SC prostanoid therapy to oral or inhaled therapies is safe on the long-term in selected children, identified by reaching hemodynamic criteria for durable IV/SC prostanoid discontinuation while on IV/SC prostanoid therapy.