Karan R. Kumar, Elizabeth C. Ciociola, Kayla R. Skinner, Gargi M. Dixit, Sunshine Alvarez, Elijah K. Benjamin, Jeffrey C. Faulkner, Rachel G. Greenberg, Reese H. Clark, Daniel K. Benjamin Jr, Christoph P. Hornik, Jan Hau Lee
Duke University School of Medicine. University of North Carolina School of Medicine. Pediatrix Center for Research. KK Women’s and Children’s Hospital. Duke-NUS School of Medicine.
United States and Singapore
Cardiology in the Young
Cardiol Young 2024;
DOI: 10.1017/S1047951124025976
Abstract
Background: New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods: We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.
Results: Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion: Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
Category
Class I. Persistent Pulmonary Hypertension of the Newborn
Class III. Pulmonary Hypertension Associated with Lung Disease
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes