Rubin Lewis J, Badesch David B, Barst Robyn J, Galie Nazzareno, Black Carol M, Keogh Anne, Pulido Tomas, Frost Adaani, Roux Sebastien, Leconte Isabelle, Landzberg Michael, Simonneau Gerald
Division of Pulmonary and Critical Care Medicine, University of California at San Diego, La Jolla 92037-1330, USA.
N Engl J Med. 2002 Mar 21;346(12):896-903. doi: 10.1056/NEJMoa012212.
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.
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 62.5 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.
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<0.001). Bosentan also improved the Borg dyspnea index and WHO functional class and increased the time to clinical worsening.
The endothelin-receptor antagonist bosentan is beneficial in patients with pulmonary arterial hypertension and is well tolerated at a dose of 125 mg twice daily. Endothelin-receptor antagonism with oral bosentan is an effective approach to therapy for pulmonary arterial hypertension.
内皮素-1是一种强效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。本试验在更多患者中研究了波生坦对运动能力的影响，并比较了两种剂量。
在这项双盲、安慰剂对照研究中，我们将213例肺动脉高压（原发性或与结缔组织病相关）患者随机分配，使其接受安慰剂或每日两次服用62.5mg波生坦，持续4周，随后接受两种剂量（每日两次125mg或250mg）中的一种，持续至少12周。主要终点是运动能力的变化程度。次要终点包括Borg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时间。
在第16周时，接受波生坦治疗的患者六分钟步行距离有所改善；安慰剂组与波生坦联合治疗组之间的平均差异为44m（95%置信区间，21至67；P<0.001）。波生坦还改善了Borg呼吸困难指数和WHO功能分级，并延长了临床恶化时间。
内皮素受体拮抗剂波生坦对肺动脉高压患者有益，且每日两次服用125mg的剂量耐受性良好。口服波生坦进行内皮素受体拮抗是治疗肺动脉高压的有效方法。
