Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension - Twelve-month clinical trial of a single-drug, open-label, pilot study

Background - Pulmonary arterial hypertension ( PAH) is a progressive and fatal disease. Sildenafil is a type 5 phosphodiesterase inhibitor and pulmonary vasodilator. Therefore, we hypothesized that sildenafil would improve distance walked in 6 minutes and hemodynamics in children with PAH. Methods and Results - After baseline assessment of hemodynamics by cardiac catheterization and distance walked in 6 minutes, we administered oral sildenafil at 0.25 to 1 mg/ kg 4 times daily to 14 children ( median age, 9.8 years; range, 5.3 to 18). Diagnoses were primary ( n = 4) and secondary ( n = 10) PAH. We repeated the 6- minute walk test at 6 weeks and at 3, 6, and 12 months ( n = 14) and cardiac catheterization ( n = 9) after a median follow- up of 10.8 months ( range, 6 to 15.3). During sildenafil therapy, the mean distance walked in 6 minutes increased from 278 +/- 114 to 443 +/- 107 m over 6 months ( P = 0.02), and at 12 months, the distance walked was 432 +/- 156 m ( P = 0.005). A plateau was reached between 6 and 12 months ( P = 0.48). Mean pulmonary artery pressure decreased from a median of 60 mm Hg ( range, 50 to 105) to 50 mm Hg ( range, 38 to 84) mm Hg ( P = 0.014). Median pulmonary vascular resistance decreased from 15 Wood units m(2) ( range, 9 to 42) to 12 Wood Units m2 ( range, 5 to 29) ( P = 0.024). Conclusions - Oral sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with PAH. Confirmation of these results in a randomized, controlled trial is essential.