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| |  Sildenafil Effective for Pulmonary Hypertension in Children Without Sickle-Cell Disease: Presented at ERS By Evelyn Harvey VIENNA, Austria -- September 15, 2009 -- Sildenafil treatment can improve peak oxygen consumption (VO2) and World Health Organization (WHO) functional class in paediatric patients with pulmonary arterial hypertension (PAH), according to a study presented here at the 19th Annual Congress of the European Respiratory Society (ERS). However, the use of sildenafil for pulmonary hypertension in children with sickle-cell disease (SCD) was recently halted due to safety concerns. The walk-Pulmonary Hypertension and Sickle Cell Disease With Sildenafil Therapy (walk-PHaSST) studies were presented by Robyn Barst, MD, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, on September 13. Part of the study examined the efficacy and safety of oral sildenafil in 234 children with idiopathic, familial, or congenital heart disease-related PAH. Patients were randomised to receive a low, medium, or high oral dose of sildenafil or placebo 3 times daily for 16 weeks. The actual dose was dependent on the child’s weight. All children weighed >=8 kg and were aged 1 to 17 years, with no other significant conditions such as HIV or SCD. Peak VO2 was assessed at baseline and 16 weeks by cycle ergometry in the 50% of patients capable of the test. In the combined sildenafil treatment groups, the percent change in peak VO2 was significantly improved from baseline at 16 weeks (P = .056). A mean change of 7.7% was observed, comprising 3.8%, 11.3%, and 8.0%, for the low, medium, and high sildenafil groups, respectively. Improvements in haemodynamics, functional class, and global physician and parent assessments were also noted in the sildenafil groups. Sildenafil was well tolerated, with 6 discontinuations and 11 serious adverse events (AEs), 2 of which were drug-related. Pulmonary hypertension is a recognised complication of SCD, with increased tricuspid regurgitant jet velocity associated with greater mortality. Therefore, researchers also assessed the safety and efficacy of sildenafil in 132 patients with SCD patients who were given placebo or sildenafil on an escalating scale of 20, 40, 80 mg, orally, 3 times daily for 16 weeks. The interim analysis showed an unacceptably high occurrence of serious and other adverse events in patients with SCD. Most were sickle-cell pain crises and the study was therefore terminated. “These findings from walk-PHaSST should not be applied to other PAH groups in whom sildenafil has been proven safe and efficacious,” cautioned Dr. Barst. Sildenafil is effective and well tolerated in paediatric PAH patients. It appears that the safety profile is unacceptable in patients with SCD and PH, leaving an unmet need for further investigation. [Presentation title: Oral Sildenafil Treatment in Children With Pulmonary Arterial Hypertension (PAH): Results of a Double-Blind, Placebo-Controlled, Dose-Ranging Study: Abstract 4794. and Treatment of Pulmonary Hypertension (PH) and Sickle Cell Disease (SCD) With Sildenafil (Sild) Therapy (walk-PHaSST): Interim Report. Abstract 171]
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