Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension
Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension
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DOI：
10.1186/s12872-017-0569-3
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发表时间：
2017-07-04
影响因子：
2.1
通讯作者：
Zhang, Min
中科院分区：
文献类型：
--
作者：
Beghetti, Maurice;Rudzinski, Andrzej;Zhang, Min
背景：尽管唐氏综合征儿童发生肺动脉高压的风险增加，但这些患者对肺动脉高压靶向治疗的反应并不是很好。西地那非治疗1-17岁的肺动脉高压儿童(STARTS-1)试验是一项剂量范围的研究，目的是研究口服西地那非治疗儿童肺动脉高压的短期疗效和安全性。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的安全性和有效性。方法：这是一项对参加STARTS-1试验的唐氏综合征合并肺动脉高压的儿童进行的事后分析。分别在治疗前和治疗16周后测定平均肺动脉压(MPAP)、肺血管阻力指数(PVRI)和心脏指数(CI)。结果：在STARTS-1试验中随机选择的234例患者中，48例(20.5%)出现唐氏综合征。尽管与安慰剂相比，西地那非在非唐氏综合症患者和发育有运动能力的儿童中产生了与剂量相关的PVRI和mPAP降低，但在唐氏综合症患者中这一点并不令人满意。与安慰剂相比，PVRI与剂量相关的减少发生在所有亚组中，唐氏综合征亚组除外。西地那非在唐氏综合征亚群中耐受性良好，最常见的不良反应与整个START-1人群的报道相似。结论：西地那非治疗16周对唐氏综合征合并肺动脉高压的儿童的PVRI或mPAP没有影响。结果表明，唐氏综合征儿童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不完全研究可能引入了潜在的偏见。
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.