Sitaxsentan therapy for pulmonary arterial hypertension
Sitaxsentan therapy for pulmonary arterial hypertension
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DOI：
10.1164/rccm.200307-957oc
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发表时间：
2004-02-15
影响因子：
24.7
通讯作者：
Frumkin, LR
中科院分区：
文献类型：
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作者：
Barst, RJ;Langleben, D;Frumkin, LR
西他森坦可能通过阻断内皮素-A的血管收缩作用，同时维持内皮素-B受体的血管扩张/清除功能，从而使肺动脉高压患者受益。将60例合并结缔组织病或先天性心脏病的特发性肺动脉高压患者随机分为安慰剂组(60例)、西塔森坦100 mg组(55例)、西塔森坦300 mg组(63例)，每日1次口服，疗程12周。主要终点是12周时Vo(2)峰值的变化。次要终点包括步行6分钟，纽约心脏协会分级，无氧阈值Vo(2)，无氧阈值每二氧化碳产量VE，血流动力学，生活质量和临床恶化时间。虽然300毫克组与安慰剂组相比，峰值Vo(2)升高(+3.1%，p<；0.01)，但心肺运动试验的其他终点均未达到。然而，与安慰剂相比，100毫克和300毫克剂量都增加了6分钟的步行距离(100毫克：+35米，p<；0.01；300 mg：+33 m，p<；0.01)；功能分级、心脏指数和肺血管阻力也有所改善(两种剂量每个参数均为0.02)。安慰剂组、100毫克组和300毫克组谷草转氨酶升高的发生率分别为3%、0%和10%。
Sitaxsentan may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictor effects of endothelin-A while maintaining the vasodilator/clearance functions of endothelin-B receptors. Patients with pulmonary arterial hypertension that was idiopathic, related to connective tissue disease or congenital heart disease, were randomized to receive placebo (n = 60), sitaxsentan 100 mg (n = 55), or sitaxsentan 300 mg (n = 63) orally once daily for 12 weeks. The primary endpoint was change in peak Vo(2) at Week 12. Secondary endpoints included 6-minute walk, New York Heart Association class, Vo(2) at anaerobic threshold, VE per carbon dioxide production at anaerobic threshold, hemodynamics, quality of life, and time to clinical worsening. Although the 300-mg group increased peak Vo(2) compared with placebo (+3.1%, p < 0.01), none of the other endpoints derived from cardiopulmonary exercise testing were met. However, both the 100-mg dose and the 300-mg dose, compared with placebo, increased 6-minute walk distance (100 mg: +35 m, p < 0.01; 300 mg: +33 m, p < 0.01); functional class, cardiac index, and pulmonary vascular resistance also improved (p < 0.02 for each parameter at both doses). The incidence of elevated aminotransferase values (> three times normal) was 3% for the placebo group, 0% for the 100-mg group, and 10% for the 300-mg group.