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 (n4) and secondary (n10) PAH. We repeated the 6-minute walk test at 6 weeks and at 3, 6, and 12 months (n14) and cardiac catheterization (n9) 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 278114 to 443107 m over 6 months (P0.02), and at 12 months, the distance walked was 432156 m (P0.005). A plateau was reached between 6 and 12 months (P0.48). 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 (P0.014). Median pulmonary vascular resistance decreased from 15 Wood units m2 (range, 9 to 42) to 12 Wood Units m2 (range, 5 to 29) (P0.024). 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. (Circulation. 2005;111: 3274-3280.