Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension

Abstract

BackgroundDespite the increased risk for pulmonary hypertension in children with Down syndrome, the response to treatment with targeted therapies for pulmonary hypertension in these patients is not well characterized. The Sildenafil in Treatment-naive children, Aged 1–17 years, with pulmonary arterial hypertension (STARTS-1) trial was a dose-ranging study of the short-term efficacy and safety of oral sildenafil in children with pulmonary arterial hypertension. We assessed the safety and efficacy of oral sildenafil in children with Down syndrome and pulmonary arterial hypertension.MethodsThis was a post-hoc analysis of children with Down syndrome and pulmonary arterial hypertension enrolled in the STARTS-1 trial. Mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), and cardiac index (CI) were assessed at baseline and following 16 weeks of treatment with sildenafil.ResultsOf 234 patients randomized and treated in the STARTS-1 trial, 48 (20.5%) had Down syndrome. Although sildenafil produced dose-related reductions in PVRI and mPAP, compared with placebo, in non–Down syndrome patients and children developmentally able to exercise, this was not satisfactorily marked in patients with Down syndrome. The dose-related reductions in PVRI, compared with placebo, occurred in all subgroups, with the exception of the Down syndrome subgroup. Sildenafil appeared to be well tolerated in the Down syndrome subpopulation and the most frequently reported AEs were similar to those reported for the entire STARTS-1 population.ConclusionSildenafil treatment for 16 weeks had no effect on PVRI or mPAP in children with Down syndrome and pulmonary arterial hypertension. The results suggest that children with Down syndrome may be less responsive to sildenafil for pulmonary arterial hypertension, but the incomplete work-up for the etiology of pulmonary arterial hypertension may have introduced a potential bias.Trial registrationStudy received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-017-0569-3) contains supplementary material, which is available to authorized users.

Postoperative and long‐term outcomes in children with Trisomy 21 and single ventricle palliation

“…Preventative education and screening and treatment of obstructed breathing in T21 patients may be critical for maximizing the potential of the Fontan circulation. Adjunctive treatment TA B L E 5 Comparison of characteristics between long-term Fontan survivors with T21 vs no known genetic anomaly with pulmonary vasodilators 24,25 may be important to improve the longevity of the Fontan circulation in patients with T21.…”

Management dilemmas in pulmonary arterial hypertension associated with congenital heart disease

“… 80 , 81 Furthermore, the recent Sildenafil in Treatment-Naive Children, Aged 1–17 Years, with Pulmonary Arterial Hypertension (STARTS-1) dose-finding trial of sildenafil in paediatric PAH failed to demonstrate a significant haemodynamic improvement in 48 people with DS. 82 The choice of PAH therapy depends on various parameters. The requirement for monthly blood monitoring with bosentan therapy can be problematic for some.…”

Pulmonary vascular resistance index: Getting the units right and why it matters

“…Other clinical areas where PVRI plays an important role include: choice of pharmacotherapy in the medical management of pulmonary hypertension, vasopressor selection in critically ill patients, and hemodynamic assessment in the perioperative period …”

“…choice of pharmacotherapy in the medical management of pulmonary hypertension, vasopressor selection in critically ill patients, and hemodynamic assessment in the perioperative period. [20][21][22][23] Thus, we contend that a concerted effort should be made by the editorial staff of academic journals and texts to encourage the use of consistent units to define PVRI. We believe that doing so will greatly facilitate the communication and comprehension of scientific literature and help to prevent erroneous diagnosis or clinical decisions.…”