Current treatment options in children with pulmonary arterial hypertension and experiences with oral bosentan
Current treatment options in children with pulmonary arterial hypertension and experiences with oral bosentan
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DOI：
10.1111/j.1365-2362.2006.01681.x
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发表时间：
2006-09-01
影响因子：
5.5
通讯作者：
Beghetti, M.
中科院分区：
文献类型：
--
作者：
Beghetti, M.
肺动脉高压(PAH)是一种以血管收缩和肺动脉壁进行性重塑为特征的危及生命的疾病，可导致右室衰竭和死亡。特发性PAH和合并先天性心脏病的PAH在儿童PAH患者中占大多数。在过去的几十年里，已经介绍了几种药理学方法，包括钙通道阻滞剂(CCBS)、前列环素类似物、内皮素受体拮抗剂以及最近的磷酸二酯酶抑制剂。本文综述了儿童可用的治疗方案，特别是波生坦的初始体验。尽管CCB已被证明可以提高IPAH的存活率，但其有益效果似乎仅限于少数患者，他们被定义为对血管反应性测试的“反应者”。随着前列环素(静脉注射前列环素)和前列环素类似物的使用，治疗选择显著增加，特别是在传统治疗无效的患者中。尽管埃博司汀已被证明对PAH有效，但由于侵入性使用模式引起的严重并发症，特别是在儿童中，该药物并不理想。磷酸二酯酶-5抑制剂也显示出了有益的效果。波生坦以口服双ETA/ETB受体拮抗剂为靶向ET系统，已被证明可以改善成年PAH患者的心肺血流动力学、运动能力、生活质量和生存。特定的ETA拮抗剂也可能呈现出同样的益处。最近波生坦在儿科PAH患者中的应用经验表明，在成人患者中获得的结果可能会外推到儿童，从而提供一种易于管理的安全有效的治疗方法。
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by vasoconstriction and progressive remodelling of the pulmonary arterial wall leading to right ventricular failure and death. Idiopathic PAH (IPAH) and PAH associated with congenital heart defects account for the majority of paediatric patients with PAH. During the last few decades, several pharmacological approaches have been introduced, including calcium channel-blockers (CCBs), prostacyclin analogues, endothelin receptor antagonists and, most recently, phosphodiesterase inhibitors.This paper reviews the treatment options available to children with a special focus on the initial experience with bosentan. Although CCBs have been shown to increase survival in IPAH, the beneficial effect appears to be limited to a small number of patients, defined as 'responders' to the vasoreactivity testing. With the availability of prostacyclin (intravenous epoprostenol) and then prostacyclin analogues, the treatment options have increased markedly and particularly in patients who have not responded to conventional therapy. Although epoprostenol has been shown to be efficacious in PAH, the drug is not ideal owing to serious complications arising from the invasive mode of application, particularly in children. Phosphodiesterase-5 inhibitors have also shown beneficial effects. Targeting the endothelin (ET) system with the oral, dual ETA/ETB receptor antagonist, bosentan has been demonstrated to improve the cardiopulmonary haemodynamics, exercise capacity, quality-of-life and survival in adult patients with PAH. Specific ETA antagonists may also present the same beneficial profile. Recent experience with bosentan in paediatric patients with PAH indicates that the results obtained in adult patients may be extrapolated to children, thus offering a safe and effective therapy that is easy to administer.