title: Comparative effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus.
abstract: BACKGROUND
  Patent ductus arteriosus (PDA) is common in extremely premature infants and associated with increased morbidity and mortality. Medical management of PDA uses either indomethacin or ibuprofen. Despite numerous studies, uncertainty exists as to which drug is safer or more effective; we sought to fill this knowledge gap.
  
  
  METHODS
  We identified infants <28weeks gestational age discharged from neonatal intensive care units included in the Pediatrix Medical Group Clinical Data Warehouse between 2006 and 2012 who were treated with indomethacin or ibuprofen between postnatal days 2 and 14. Infants treated with both drugs or infants with a congenital malformation were excluded. We used multivariable logistic regression to determine the association of indomethacin versus ibuprofen on clinical outcomes.
  
  
  RESULTS
  Of 6349 patients who met study criteria, 1177 (19%) received ibuprofen and 5172 (81%) received indomethacin. The median gestational age was 25weeks (interquartile range 24-26), and 2894 (46%) infants were <750g at birth. On unadjusted analysis, infants who received ibuprofen had significantly higher incidences of death prior to discharge, surgical ligation of the PDA prior to discharge, death or spontaneous intestinal perforation within 7days of therapy, death or surgical ligation of the PDA prior to discharge, and an elevated creatinine within 7days of treatment. However, on multivariable analysis, no significant differences in outcomes were observed (odds ratio for death/PDA ligation for ibuprofen vs. indomethacin=1.12 [95% CI 0.91-1.39]).
  
  
  CONCLUSIONS
  We observed similar effectiveness and safety profiles for indomethacin and ibuprofen in the medical management of PDA in premature infants.
authors.affiliation: Department of Surgery, Duke University School of Medicine, Durham, NC, United States.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Gulack
authors.affiliation: Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Laughon
authors.affiliation: Pediatrix Medical Group, Inc., Sunrise, FL, United States.
authors.forename: Reese H
authors.initials: RH
authors.lastname: Clark
authors.affiliation: Pediatrix Medical Group, San Jose, CA, United States.
authors.forename: Meera N
authors.initials: MN
authors.lastname: Sankar
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States.
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hornik
authors.affiliation: Department of Pediatrics, Duke University School of Medicine, Durham, NC, United States; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, United States. Electronic address: brian.smith@duke.edu.
authors.forename: P Brian
authors.initials: PB
authors.lastname: Smith
mesh_terms: D002317:Cardiovascular Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016208:Databases, Factual; D004374:Ductus Arteriosus, Patent / Q000188:drug therapy*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use*; D007213:Indomethacin / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D008297:Male; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents; D007052:Ibuprofen; D007213:Indomethacin
keywords: Bronchopulmonary dysplasia; Medical management; Mortality; Premature infants