Gatzoulis Michael A, Beghetti Maurice, Galiè Nazzareno, Granton John, Berger Rolf M F, Lauer Andrea, Chiossi Eleonora, Landzberg Michael
Royal Brompton Hospital and the National Heart and Lung Institute, Imperial College, London, UK.
Int J Cardiol. 2008 Jun 23;127(1):27-32. doi: 10.1016/j.ijcard.2007.04.078. Epub 2007 Jul 20.
Bosentan, an oral endothelin ET(A)/ET(B) receptor antagonist, improves hemodynamics and exercise capacity in patients with Eisenmenger syndrome but longer-term effects are unknown. This study investigated the efficacy and safety of bosentan up to 40 weeks in these patients.
Following the 16-week, double blind, placebo-controlled BREATHE-5 study of bosentan in patients with Eisenmenger syndrome, an open-label extension (OLE) was performed. Patients who completed BREATHE-5 received bosentan for an additional 24 weeks (62.5 mg b.i.d. for 4 weeks, then 125 mg b.i.d.) and were analyzed in two groups; ex-placebo and ex-bosentan, according to BREATHE-5 treatment.
Thirty-seven patients with Eisenmenger syndrome who participated in BREATHE-5 were included in the OLE. At week 24, the 6-minute walk distance (mean+/-SE) increased from OLE baseline for the ex-placebo (+33.2+/-23.9 m) and ex-bosentan group (+6.7+/-10.0 m). The overall improvement from baseline of BREATHE-5 was +61.3+/-8.1 m (95% confidence interval: [44.7, 78.0]) for the ex-bosentan group. WHO functional class was improved in both groups. Bosentan did not reduce systemic arterial blood oxygen saturation; safety profile was comparable to previous trials.
In conclusion, these longer follow-up data support the efficacy and safety profile reported in the preceding BREATHE-5 study of bosentan treatment of Eisenmenger syndrome, challenging the notion that pulmonary vascular disease and severe functional impairment in these patients are not amenable to therapy.
波生坦是一种口服内皮素ET(A)/ET(B)受体拮抗剂，可改善艾森曼格综合征患者的血流动力学和运动能力，但长期效果尚不清楚。本研究调查了波生坦在这些患者中长达40周的疗效和安全性。
在为期16周的波生坦治疗艾森曼格综合征患者的双盲、安慰剂对照BREATHE-5研究之后，进行了一项开放标签扩展研究（OLE）。完成BREATHE-5研究的患者再接受24周的波生坦治疗（第1至4周62.5毫克，每日两次，之后125毫克，每日两次），并根据BREATHE-5研究中的治疗情况分为两组进行分析，即原接受安慰剂治疗组和原接受波生坦治疗组。
37名参与BREATHE-5研究的艾森曼格综合征患者纳入了开放标签扩展研究。在第24周时，原接受安慰剂治疗组的6分钟步行距离（均值±标准误）较开放标签扩展研究基线增加了（+33.2±23.9米），原接受波生坦治疗组增加了（+6.7±10.0米）。原接受波生坦治疗组自BREATHE-5研究基线的总体改善为+61.3±8.1米（95%置信区间：[44.7, 78.0]）。两组患者的世界卫生组织功能分级均得到改善。波生坦未降低体循环动脉血氧饱和度；安全性与先前试验相当。
总之，这些更长时间的随访数据支持了先前BREATHE-5研究中报道的波生坦治疗艾森曼格综合征的疗效和安全性，对这些患者的肺血管疾病和严重功能障碍无法治疗这一观念提出了挑战。
