New research shows that sildenafil, which is currently approved for adult pulmonary arterial hypertension (PAH), may also provide significant benefits for children with PAH, helping to improve both oxygen delivery and exercise capacity. The study, presented at CHEST 2011, the 77th annual meeting of the American College of Chest Physicians, is the first that has “adequately evaluated” a drug for the treatment of PAH in children, according to the researchers.

In a randomized double-blind study involving 32 medical centers in 16 countries, researchers assessed the outcomes of sildenafil therapy in 234 children (aged 1 to 17 years) with PAH. The children received low-, medium-, and high-dose sildenafil, or placebo for 16 weeks. Cardiopulmonary exercise testing, peak oxygen consumption (pVO2), and minute ventilation to carbon dioxide output (VE/VCO2) levels were determined at baseline and at week 16 in all children who could reliably exercise on a bicycle (n=106).

Although the primary endpoint of percentage change in pVO2 did not meet predefined criteria (p=0.056), children receiving sildenafil therapy at medium and high dose had greater improvements in pVO2 and VE/VCO2 slope (ie, the relationship between the two variables) versus placebo, signifying an improvement in both oxygen delivery and blood flow through the lungs. Sildenafil also increased the amount of exercise the children could perform and made it easier for them to exercise. In addition, sildenafil improved the gas exchange efficiency of the lungs during exercise.

Outcomes appeared better for patients with idiopathic/heritable PAH versus congenital heart defect-associated PAH. Long-term follow up of these patients 3 years after the initial trial revealed a concern for increased mortality in the high dose group, suggesting that the medium dose may have the best risk-benefit ration.

Sildenafil is not yet approved for use in pediatric patients with PAH, and the researchers caution that this study is only the first step to evaluate the safety and effectiveness of treatments for children.

Source: American College of Chest Physicians