Johannes M. Douwes, Willemijn M. H. Zijlstra, Erika B. Rosenzweig, Mark-Jan Ploegstra, Usha S. Krishnan, Meindina G. Haarman, Marcus T. R. Roofthooft, Douwe Postmus, Hans L. Hillege, D. Dunbar Ivy, Rolf M. F. Berger
University of Groningen, University Medical Center Groningen and Beatrix Children’s Hospital. Columbia University. University of Colorado, Children’s Hospital Colorado.
Netherlands and United States
Annals of the American Thoracic Society
Ann Am Thorac Soc 2022; 19: 227-237
DOI: 10.1513/AnnalsATS.202012-1563OC
Abstract
Rationale: There are currently no data supporting specific dosing and weaning strategies for parenteral 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 who 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 receiver operating characteristic analyses showed specific hemodynamic criteria at discontinuation of IV/SC prostanoids (mean pulmonary arterial pressure < 35 mm Hg and/or pulmonary vascular resistance index < 4.4 Wood units [WU]⋅m2) identified children with favorable long-term outcome after IV/SC prostanoid discontinuation, compared with patients who do not meet those criteria (P = 0.027). In the children who continued IV/SC prostanoids until the end of follow-up, higher dose (>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 in the long term in selected children, identified by reaching hemodynamic criteria for durable IV/SC prostanoid discontinuation while on IV/SC prostanoid therapy.
Category
Medical Therapy. Efficacy or Lack of Efficacy
Diagnostic Testing for Pulmonary Vascular Disease. Invasive Testing
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
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