Pulmonary Hypertension Therapy and a Systematic Review of Efficacy and Safety of PDE-5 Inhibitors.

Pulmonary hypertension (PH) is a syndrome that is of growing concern to pediatricians worldwide. Recent data led to concerns about the safety of phosphodiesterase type 5 (PDE5) inhibitors in children and a US Food and Drug Administration safety advisory. Our objective is to provide insight into therapies for PH in children and to systematically review the comparative effectiveness and safety of PDE5 inhibitors in the management of pediatric patients with PH. We searched the following databases through February 2015: Medline, Embase, SCOPUS, and the Cochrane Central Register of Controlled Trials. We included studies that examined PDE5 inhibitor use in children with PH. Allowed comparators were either no medication or other classes of medication for management of PH. Study inclusion was via a 2-stage process with 2 reviewers and a predesigned form. Of 1270 papers identified by the literature search, 21 were included: 8 randomized controlled trials and 13 observational studies (9 retrospective, 4 prospective). There is strong evidence that PDE5 inhibitor use improves echocardiography measurements, cardiac catheterization parameters, and oxygenation compared with baseline or placebo in pediatric patients with PH. Evidence suggests that low- and moderate-dose sildenafil are safe regimens for children. There are a relatively small number of randomized controlled trials that address use of PDE5 inhibitors in pediatric patients with PH. PDE5 inhibitors are effective agents for cardiovascular and oxygenation end points in pediatric PH and important components of a multimodal pharmacotherapeutic approach to this growing challenge. Additional studies are needed to define optimal PH therapy in childhood.