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BMC Cardiovascular Disorders
Published in: BMC Cardiovascular Disorders 1/2017

Open Access 01-12-2017 | Research article

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

Authors: Maurice Beghetti, Andrzej Rudzinski, Min Zhang

Published in: BMC Cardiovascular Disorders | Issue 1/2017

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Abstract

Background

Despite 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.

Methods

This 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.

Results

Of 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.

Conclusion

Sildenafil 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 registration

Study received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913.
Appendix
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Metadata
Title
Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension
Authors
Maurice Beghetti
Andrzej Rudzinski
Min Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2017
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-017-0569-3

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