Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study
Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study
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DOI：
10.1016/s0140-6736(01)06250-x
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发表时间：
2001-10-06
期刊：
影响因子：
168.9
通讯作者：
Rubin, LJ
中科院分区：
文献类型：
--
作者：
Channick, RN;Simonneau, G;Rubin, LJ
背景内皮素1是一种强有力的内源性血管收缩剂和丝裂原，可能是肺动脉高压的原因之一。我们描述了波生坦的有效性和安全性，波生坦是一种双重内皮素受体拮抗剂，可以口服，在严重的肺动脉高压患者。32例肺动脉高压患者（原发性或与硬皮病相关）随机分配至波生坦组（62.5 mg，每日两次，持续4周，然后125 mg，每日两次）或安慰剂，至少持续12周。主要终点是运动能力的变化。次要终点包括心肺血流动力学变化、博格呼吸困难指数、WHO功能分级和因临床恶化而退出研究。结果在给予波生坦的患者中，与基线相比，6分钟步行距离在12周时改善了70米，而安慰剂组患者则恶化了6米（差异76米[95%CI 12-139]，p = 0.021）。这种改善至少维持了20周。波生坦组的心脏指数比安慰剂组高1.0 L min（-1）m（-2）（95% CI 0.6-1.4，p < 0.0001）。波生坦组肺血管阻力降低了223 dyn s cm（-5），而安慰剂组增加了191 dyn s cm（-5）（差异为-415 [-608至-221]，p = 0.0002）。接受波生坦治疗的患者博格呼吸困难指数降低，WHO功能分级改善。所有3例因临床恶化而退出研究的患者均在安慰剂组（p = 0.033）。两组之间不良事件的数量和性质没有差异。解释波生坦增加运动能力，改善肺动脉高压患者的血流动力学，表明内皮素在肺动脉高压中具有重要作用。
Background Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension. We describe the efficacy and safety of bosentan, a dual endothelin-receptor antagonist that can be taken orally, in patients with severe pulmonary hypertension.Methods In this double-blind, placebo-controlled study, 32 patients with pulmonary hypertension (primary or associated with scleroderma) were randomly assigned to bosentan (62.5 mg taken twice daily for 4 weeks then 125 mg twice daily) or placebo for a minimum of 12 weeks. The primary endpoint was change in exercise capacity. Secondary endpoints included changes in cardiopulmonary haemodynamics, Borg dyspnoea index, WHO functional class, and withdrawal due to clinical worsening. Analysis was by intention to treat.Findings In patients given bosentan, the distance walked in 6 min improved by 70 m at 12 weeks compared with baseline, whereas it worsened by 6 m in those on placebo (difference 76 m [95% Cl 12-139], p = 0.021). The improvement was maintained for at least 20 weeks. The cardiac index was 1.0 L min(-1) m(-2) (95% Cl 0.6-1.4, p < 0.0001) greater in patients given bosentan than in those given placebo. Pulmonary vascular resistance decreased by 223 dyn s cm(-5) with bosentan, but increased by 191 dyn s cm(-5) with placebo (difference -415 [-608 to -221], p = 0.0002). Patients given bosentan had a reduced Borg dyspnoea index and an improved WHO functional class. All three withdrawals from clinical worsening were in the placebo group (p = 0.033). The number and nature of adverse events did not differ between the two groups.Interpretation Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension.