Beghetti Maurice, Rudzinski Andrzej, Zhang Min
Pediatric Cardiology Unit, Department of Child and Adolescent, University of Geneva, Geneva, Switzerland.
Pediatric Cardiology, Jagiellonian University, Gołębia 24, 31-007, Cracow, Poland.
BMC Cardiovasc Disord. 2017 Jul 4;17(1):177. doi: 10.1186/s12872-017-0569-3.
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.
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.
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.
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.
Study received, September 8, 2005 (retrospectively registered); Study start, August 2003; ClinicalTrials.gov identifier, NCT00159913 .
尽管唐氏综合征患儿患肺动脉高压的风险的风险增加，但这些患者接受肺动脉高压靶向治疗的反应尚未得到充分描述。“1 - 17岁初治肺动脉高压患儿西地那非治疗研究（STARTS - 1）”试验是一项关于口服西地那非治疗肺动脉高压患儿短期疗效和安全性的剂量范围研究。我们评估了口服西地那非治疗唐氏综合征合并肺动脉高压患儿的安全性和疗效。
这是一项对参与STARTS - 1试验的唐氏综合征合并肺动脉高压患儿的事后分析。在基线期以及西地那非治疗16周后，评估平均肺动脉压（mPAP）、肺血管阻力指数（PVRI）和心脏指数（CI）。
在STARTS - 1试验中随机分组并接受治疗的234例患者中，48例（20.5%）患有唐氏综合征。尽管西地那非使非唐氏综合征患者以及发育上能够运动的儿童的PVRI和mPAP出现了与剂量相关的降低，但与安慰剂相比，在唐氏综合征患者中这种降低并不明显。与安慰剂相比，除唐氏综合征亚组外，所有亚组的PVRI均出现了与剂量相关的降低。西地那非在唐氏综合征亚组中似乎耐受性良好，最常报告的不良事件与整个STARTS - 1人群报告的相似。
西地那非治疗16周对唐氏综合征合并肺动脉高压患儿的PVRI或mPAP没有影响。结果表明，唐氏综合征患儿对西地那非治疗肺动脉高压的反应可能较差，但对肺动脉高压病因的检查不完整可能引入了潜在偏倚。
研究于2005年9月8日接收（追溯注册）；研究开始于2003年8月；ClinicalTrials.gov标识符，NCT00159913 。
