High-dose oral ibuprofen may be most likely to result in closure of hemodynamically significant patent ductus arteriosus (PDA) in preterm infants, compared with other pharmacological treatments, according to results of a recent systematic review and meta-analysis.

However, using placebo or no treatment at all did not increase the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage in the study, published in JAMA .

“This raises the question whether active pharmacological closure of hemodynamically significant PDA necessarily improves clinical outcomes,” wrote Souvik Mitra, MD , of Dalhousie University, Halifax, N.S., and his coauthors.

PDA is a common cardiovascular issue among prematurely born infants. According to Dr. Mitra and his coauthors, it’s thought that a large proportion of PDAs spontaneously close in a few days and have minimal effect on clinical outcomes.

As a result, treatment is often targeted to PDAs deemed hemodynamically significant based on clinical and echocardiographic parameters, the authors wrote, although there is little guidance on what, if any, treatment to use in this situation.

“The dilemma is whether to use pharmacotherapy at all, and if a decision is made to treat the PDA medically, what should be the ideal choice of pharmacotherapy,” they wrote.

Dr. Mitra and colleagues conducted a systematic review and meta-analysis of 68 randomized clinical trials including 4,802 infants with clinically or echocardiographically diagnosed, hemodynamically significant PDA.

They found that closure of hemodynamically significant PDA was significantly more likely with high-dose oral ibuprofen, compared with the two of the most widely used treatments, namely standard-dose intravenous ibuprofen (odds ratio, 3.59) and standard-dose intravenous indomethacin (odds ratio, 2.35).

Despite that finding, there was no significant difference in the odds of mortality, necrotizing enterocolitis, or intraventricular hemorrhage for use of placebo or no treatment, compared with any of the treatment modalities, the investigators added.

“With increasing emphasis on conservative management of PDA, these results may encourage researchers to revisit placebo-controlled trials against newer pharmacotherapeutic options,” they said.

Study authors reported no relevant potential conflicts of interest.

SOURCE: Mitra S et al. JAMA. 2018;319(12):1221-38 .