Ibuprofen Versus Indomethacin for Medical Closure of the Patent Arterial Duct: A Pooled Analysis by Route of Administration

Introduction: Preterm infants are at increased risk of having a patent arterial duct (PAD). PADs may cause congestive heart failure, respiratory distress, necrotizing enterocolitis, and renal impairment. Consequently, in some infants, it becomes necessary to attempt closure of the PAD. Surgical closure can be difficult in small infants and is not without its risks; thus, medical closure offers advantages. Cyclooxygenase inhibitors have been used for medical closure of the PAD with both ibuprofen and indomethacin having been used clinically. Methods: We performed a systematic review of the literature to identify all studies comparing ibuprofen and indomethacin. Studies comparing ibuprofen and indomethacin for closure of the PAD in premature infants were included in the meta-analysis. A subanalysis was performed to compare the route of administration. Efficacy endpoints studied were PAD closure and surgical ligation while adverse effects studied were death in the first month of life, necrotizing enterocolitis, gastrointestinal bleeding, intestinal perforation, bronchopulmonary dysplasia in the first month of life, Grade 3 or 4 intraventricular hemorrhage, and change in the serum creatinine after treatment. Results: Ibuprofen and indomethacin were equally effective in closing the PAD in premature infants and demonstrated no difference in the incidence of adverse events. In respect to the route of administration, oral ibuprofen was as effective as intravenous indomethacin. When comparing both drugs via the intravenous route, the only difference noted between the ibuprofen and indomethacin was that ibuprofen was associated with a lesser increase in serum creatinine after treatment. Conclusion: Ibuprofen and indomethacin are equally effective in PAD closure without any difference in the incidence of adverse events. Importantly, oral ibuprofen was as effective as intravenous indomethacin.