Seyfarth Hans-Jurgen, Hammerschmidt Stefan, Pankau Hans, Winkler Jorg, Wirtz Hubert
Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany.
Respiration. 2007;74(3):287-92. doi: 10.1159/000093322. Epub 2006 May 11.
There is no approved pharmacological treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not suitable for pulmonary endarterectomy (PEA).
The study investigates the effect of the dual endothelin receptor antagonist bosentan on exercise tolerance (6-min walking distance, 6MWD) and right ventricular function (Tei index) in patients with CTEPH over 24 months.
Twelve consecutive patients (5 males and 7 females) with CTEPH not eligible for PEA or following partial or complete failure of PEA were included in a non-randomized, open-label prospective study. All patients were WHO class III. They were included, if progressive pulmonary hypertension was diagnosed despite best supportive treatment. Bosentan was started at 62.5 mg b.i.d. and increased to the final dose of 125 mg b.i.d.
6MWD and the Tei index were assessed every 6 months. We observed a significant increase in 6MWD from 319 +/- 85.0 m at baseline to 391 +/- 76.9 m at 6 months and a significant decrease in the Tei index from 0.39 +/- 0.10 at baseline to 0.34 +/- 0.08 at 6 months. This improvement was maintained over 24 months (6 MWD: 381 +/- 101 m; Tei index: 0.31 +/- 0.03). Six patients exhibited an improvement in WHO class at 6, 12 and 18 months, 5 demonstrated improvement at the 24-month follow-up. The remainder were stable throughout the study period.
This is the first study demonstrating a long-term beneficial effect of bosentan on exercise tolerance (6MWD) and right heart function (Tei index) in CTEPH.
对于不适合进行肺动脉内膜剥脱术（PEA）的慢性血栓栓塞性肺动脉高压（CTEPH）患者，尚无获批的药物治疗方法。
本研究调查双重内皮素受体拮抗剂波生坦对CTEPH患者超过24个月的运动耐量（6分钟步行距离，6MWD）和右心室功能（Tei指数）的影响。
12例连续的CTEPH患者（5例男性和7例女性），不符合PEA标准或PEA部分或完全失败后，被纳入一项非随机、开放标签的前瞻性研究。所有患者均为WHO III级。如果尽管进行了最佳支持治疗仍诊断为进行性肺动脉高压，则将他们纳入研究。波生坦起始剂量为62.5 mg，每日两次，最终增加至125 mg，每日两次。
每6个月评估一次6MWD和Tei指数。我们观察到6MWD从基线时的319±85.0 m显著增加到6个月时的391±76.9 m，Tei指数从基线时的0.39±0.10显著降低到6个月时的0.34±0.08。这种改善在24个月内得以维持（6MWD：381±101 m；Tei指数：0.31±0.03）。6例患者在6、12和18个月时WHO分级有所改善，5例在24个月随访时表现出改善。其余患者在整个研究期间保持稳定。
这是第一项证明波生坦对CTEPH患者的运动耐量（6MWD）和右心功能（Tei指数）具有长期有益作用的研究。
