RT Journal Article
SR Electronic
T1 Effects of oral sildenafil on exercise capacity in children with pulmonary arterial hypertension: a randomised trial
JF Open Heart
JO Open Heart
FD British Cardiovascular Society
SP e001149
DO 10.1136/openhrt-2019-001149
VO 6
IS 2
A1 Stuart Russell
A1 Maurice Beghetti
A1 Ronald Oudiz
A1 Cecile Balagtas
A1 Min Zhang
A1 Dunbar Ivy
YR 2019
UL http://openheart.bmj.com/content/6/2/e001149.abstract
AB Objective The 16-week, randomised, double-blind Sildenafil in Treatment-Naïve Children, Aged1–17 years, with Pulmonary Arterial Hypertension (STARTS-1) study assessed the effect of sildenafil on cardiopulmonary exercise testing (CPET) in treatment-naïve paediatric patients with pulmonary arterial hypertension (PAH) and included a long-term extension (STARTS-2). CPET has rarely been performed in paediatric patients and we assessed both aerobic capacity with peak oxygen consumption (PVO2) and ventilatory inefficiency with the slope of ventilation to carbon dioxide production (VE/VCO2 slope).Methods Patients (aged 1–17 year) were randomised to low (10 mg), medium (10–40 mg) and high (20–80 mg) sildenafil dose groups. Patients previously treated with placebo in STARTS-1 were randomised to one of three blinded sildenafil dose groups for STARTS-2. CPET was assessed by cycle ergometry at baseline, week 16, and year 1.Results Of the 234 children randomised, 115 could exercise. At week 16, the combined sildenafil dose group had a 7.7% increase in mean PVO2 percent change from baseline compared with placebo (95% CI −0.2% to 15.6%; p=0.056); at year 1, a significant increase in mean percent change in PVO2 from baseline was only observed in the low-dose group (mean of 12.4% and 95% CI 3% to 21.8%). For VE/VCO2 slope, at week 16, the combined dose group had a −9.7% mean change from baseline compared with placebo (95% CI −14.9% to −4.5%; p<0.001); at year 1, there were no significant changes for any dose group.Conclusions Sildenafil monotherapy (combined sildenafil dose group) appeared to improve short-term VE/VCO2 slope versus placebo but did not significantly improve PVO2 in treatment-naïve paediatric patients with PAH who were developmentally able to exercise.Trial registration number NCT00159913 for A1481131, NCT00159874 for A1481156.