Early initiation of prostanoid therapy yields favorable outcome in children with PAH

In children with pulmonary arterial hypertension, early initiation of IV or subcutaneous parenteral prostanoid therapy, higher doses of therapy and when combined with additional PAH therapy were associated with favorable outcomes.

“Currently, IV/subcutaneous prostanoids are not formally approved for children by the Europeans Medicines Agency or the U.S. FDA, but generally used as an accepted therapy in pediatric PAH,” Johannes M. Douwes, MD, PhD, from the department of pediatric cardiology at the Center for Congenital Heart Diseases at Beatrix Children’s Hospital in Groningen, the Netherlands, and colleagues wrote in Annals of the American Thoracic Society. “Also, although current guidelines provide recommendations of which patients should have IV/subcutaneous prostanoids initiated, optimal dosing remains arbitrary, as well as whether and when IV/subcutaneous prostanoids can be effectively transitioned to oral/inhaled PAH-targeted therapies.”

The multicenter, retrospective, observational study included 275 children with PAH from an international multicenter cohort and researchers retrospectively analyzed 98 of the children (mean age, 5.5 years; 57% girls) who received IV/subcutaneous prostanoid therapy.

IV/subcutaneous prostanoids were administered as monotherapy in 20% of patients or were combined with other PAH-targeted therapies as dual (46%) or as triple therapy (34%). The median time-averaged prostanoid dose was 37 ng/kg per minute.

During follow-up, 29 patients discontinued IV/subcutaneous prostanoids and transitioned to oral/inhaled PAH therapies.

Compared with children who did not meet specific hemodynamic criteria at the time of discontinuation of IV/subcutaneous prostanoid therapy, those with a mean pulmonary arterial pressure of more than 35 mm Hg and/or a pulmonary vascular resistance index of more than 4.4 Wood units had favorable long-term outcomes after discontinuation (P = .027).

The following were associated with higher transplant-free survival at 1 (93%), 3 (72%) and 5 (64%) years among the 64 children who continued their IV/subcutaneous prostanoid therapy until the end of the median 2.6 years of follow-up:

• early initiation after PAH diagnosis (HR = 1.1; 95% CI, 1.01-2; P = .022);
• higher doses of more than 25 ng/kg per minute (HR = 0.36; 95% CI, 0.17-0.74; P = .006); and
• combining prostanoidss therapy with other PAH-targeted therapies (HR = 0.04; 95% CI, 0-0.66; P = .025).

“Safe transition, also in the long term, from IV/subcutaneous prostanoid therapy to oral or inhaled therapies is possible in selected children, identified by reaching the criteria for durable IV/subcutaneous prostanoid discontinuation in addition to favorable WHO-functional class while on IV/subcutaneous prostanoid therapy,” the researchers wrote.