October 24, 2011

Sildenafil Helps Kids with PAH

(Ivanhoe Newswire) -- Sildenafil is currently approved for adult pulmonary arterial hypertension, PAH; however according to new research, the drug may also provide significant benefits for children with PAH, helping to improve both oxygen delivery and exercise capacity.

"PAH is a rare disease, and it is even more rare in children. But the disease is horrific, with the average lifespan less than one year in children if untreated; however, with appropriate treatment,  five year survival should be over 80 percent,” study author Robyn Barst, MD, Fellow of the American College of Chest Physicians, Columbia University, New York, NY, was quoted as saying.

“This is a landmark study — the first, and to date, the only study that has adequately evaluated a drug for the treatment of PAH in children.”

PAH, characterized by narrowing of the small arteries that carry blood from the heart to the lungs, leads to shortness of breath, chest pain, swelling in the lower body, fatigue, and heart failure.

PAH is rare in children and also difficult to diagnose and treat.

"Diagnosis from on set symptoms is often two years or more because patients often have nondescript symptoms such as breathlessness with exercise and fatigue," Dr. Barst was quoted as saying.  "If PAH is not suspected, the appropriate tests will not be performed until the disease has progressed, often to the point the patient has fainting episodes or heart failure."

Once PAH is diagnosed, managing the condition in children brings new challenges.  Although the disease is similar in children and adults, optimal treatment is not necessarily the same.

"Adequate clinical studies are needed to provide evidence-based treatment guidelines for children with PAH," Dr. Barst was quoted as saying regarding prescribing drugs for the treatment of PAH to children.

Dr. Barst and his colleagues studied 234 children, with PAH, between the ages of one and seventeen with PAH, from 32 different medical centers in 16 countries, to asses the outcomes of sildenafil therapy.  The children received different doses of sildenafil, or placebo, ranging from low, medium to high dose for 16 weeks.

Children receiving sildenafil therapy at medium and high dose levels had greater improvements 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.  Furthermore, sildenafil improved the gas exchange efficiency of the lungs during exercise.

However, outcomes appeared better for patients with idiopathic/heritable PAH versus congenital heart defect-associated PAH. Long-term follow-up of these patients three 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 ratio.

Although sildenafil is not yet approved for use in pediatric patients with PAH, this study is the first step to evaluate the safety and effectiveness of treatments for children.

 “The goal in treating the children is to improve their overall quality of life, in addition to hopefully improving their survival. We want to make the children feel better and not just live longer. Thus, a thorough evaluation is difficult, but it is critically important,” Dr.Barst was quoted as saying.

“Historically, PAH has been difficult to manage; however, treatments have been advancing rapidly,” David Gutterman, MD, FCCP, President of the American College of Chest Physicians was quoted as saying, “Continued research and well-controlled clinical trials should lead to further improvements in the treatment of this very challenging disease.”

SOURCE: American College of Chest Physicians, published online October 24, 2011