Bosentan therapy for pulmonary arterial hypertension
Bosentan therapy for pulmonary arterial hypertension
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DOI：
10.1056/nejmoa012212
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发表时间：
2002-03-21
影响因子：
158.5
通讯作者：
Simonneau, G
中科院分区：
文献类型：
--
作者：
Rubin, LJ;Badesch, DB;Simonneau, G
背景：内皮素-1是一种强有力的血管收缩剂和平滑肌有丝分裂原。在一项初步研究中，口服双重内皮素受体拮抗剂波生坦可改善肺动脉高压患者的运动能力和心肺血流动力学。本试验研究了波生坦对大量患者运动能力的影响，并比较了两种剂量。方法：在这项双盲安慰剂对照研究中，我们随机将213名肺动脉高压患者（原发性或与结缔组织疾病相关）接受安慰剂或接受6.25 mg波生坦每日两次，持续4周，随后接受两种剂量波生坦中的任一种（125或250 mg，每日两次），至少持续12周。主要终点是运动能力的变化程度。次要终点包括博格呼吸困难指数的变化，世界卫生组织（WHO）功能分级的变化，以及临床恶化的时间。结果：在第16周，波生坦治疗的患者6分钟步行距离有所改善;安慰剂组和联合波生坦组之间的平均差异为44 m（95%置信区间，21 - 67; P < 0.05）。
Background: Endothelin-1 is a potent vasoconstrictor and smooth-muscle mitogen. In a preliminary study, the orally administered dual endothelin-receptor antagonist bosentan improved exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary arterial hypertension. The present trial investigated the effect of bosentan on exercise capacity in a larger number of patients and compared two doses.Methods: In this double-blind, placebo-controlled study, we randomly assigned 213 patients with pulmonary arterial hypertension (primary or associated with connective-tissue disease) to receive placebo or to receive 6.25 mg of bosentan twice daily for 4 weeks followed by either of two doses of bosentan (125 or 250 mg twice daily) for a minimum of 12 weeks. The primary end point was the degree of change in exercise capacity. Secondary end points included the change in the Borg dyspnea index, the change in the World Health Organization (WHO) functional class, and the time to clinical worsening.Results: At week 16, patients treated with bosentan had an improved six-minute walking distance; the mean difference between the placebo group and the combined bosentan groups was 44 m (95 percent confidence interval, 21 to 67; P