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

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.

• Authors: 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
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) Vol. 19 Issue 2 Pg. 227-237 (02 2022) ISSN: 2325-6621 [Electronic] United States
• PMID: 34181866 (Publication Type: Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Prostaglandins
• Epoprostenol

Topics

• Antihypertensive Agents (therapeutic use)
• Child
• Epoprostenol
• Humans
• Hypertension, Pulmonary
• Prostaglandins (therapeutic use)
• Pulmonary Arterial Hypertension (drug therapy)
• Retrospective Studies
• Treatment Outcome