New Study Supports Treatment of Childhood PH with PDE-5 Inhibitors

Infants, newborns and children with pulmonary hypertension (PH) can be safely and effectively treated with phosphodiesterase type 5 (PDE-5) inhibitors, according to a new study.

The review study, “Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors,” appeared in the journal Pediatrics.

PDE-5 inhibitors such as Revatio (sildenafil) are drugs that dilate blood vessels and reduce blood pressure to improve exercise ability and reduce disease progression in PH patients.

Previous studies had raised concerns about the safety of PDE-5 inhibitors in children with PH. To address this question, researchers reviewed 21 previously published studies (including eight clinical trials and 13 observational studies) in which children with PH had received treatment with a PDE-5 inhibitor.

Researchers found strong evidence that PH children under treatment with a PDE-5 inhibitor showed improved echocardiography measurements, cardiac catheterization parameters and oxygenation compared to before treatment, or to children treated with a placebo.

“Pediatricians across the nation view the rise in pediatric pulmonary hypertension (PH) cases with growing concern because the disease can worsen, leading to right ventricular failure and death,” Chinwe Unegbu, MD, the study’s first author, said in a news release. “PH can occur in newborns, infants and children who have a number of health conditions including congenital heart disease, the most common birth defect among newborns. There are few available treatments for the growing population of children affected by this condition, so it is heartening that the evidence supports PDE-5 inhibitors for patients with PH.”

Evidence also suggests that low- and moderate-dose sildenafil may be safer regimens for PH children than longer and higher doses of this drug.

“Although there is some risk associated with PDE-5 inhibitor use by pediatric patients with PH, overwhelmingly the data indicate the benefits of using this class of drugs far outweigh the risks,” Unegbu added. “When we looked at specific clinical outcomes, we see definite improvement in a number of measures including oxygenation, hemodynamics and better clinical outcomes: The patients are doing better, feeling better and their exercise capacity rises.”

Researchers also reviewed evidence concerning safety and mortality among PH children. They found that the treatment’s most common side effects were headaches and flushing.

“With the exception of a single trial, the remaining trials included in our review did not demonstrate increased mortality in patients placed on this class of medicines, which was reassuring to us,” Unegbu said. “We can say with a good degree of confidence that providers should feel fairly comfortable prescribing PDE-5 inhibitors.”

Despite the results, researchers noted that only a few trials addressing the use of PDE5 inhibitors in pediatric PH patients, and that more studies are necessary to define what is the best PH therapy in childhood.

“Most of the studies have been conducted in adults,” Unegbu emphasized. “However, this disease unfolds in a much different fashion in children compared with adults. We are desperately in need of high-quality studies in the form of randomized controlled trials in pediatric patients and studies that examine the full range of formulations of this class of drugs.”