Seyfarth Hans-Jürgen, Pankau Hans, Hammerschmidt Stefan, Schauer Joachim, Wirtz Hubert, Winkler Jörg
Department of Pulmonary Medicine, Critical Care and Cardiology, University of Leipzig, Germany.
Chest. 2005 Aug;128(2):709-13. doi: 10.1378/chest.128.2.709.
Pulmonary arterial hypertension (PAH) is a progressive disease with a bad prognosis. Prostanoids are well established in the medical treatment of this disease. Treatment of patients with progressive disease despite prostanoids remains a therapeutic challenge. In this study, we examined the effect of adding bosentan, an endothelin antagonist, to existing prostanoid therapy on exercise capacity (6-min walking distance [6MWD]) and right ventricular (RV) function (Tei index) in patients with progressive pulmonary hypertension.
Prospective, nonrandomized, open-label study.
University hospital.
Sixteen patients with pulmonary hypertension (PAH, n = 10; pulmonary hypertension due to other cause, n = 6) with progressive disease receiving either beraprost (n = 3), inhaled iloprost (n = 10), or iloprost IV (n = 3).
Combination therapy with bosentan (final dosage, 125 mg bid) was initiated following an interval of 3-months minimum of unchanged prostanoid therapy.
Tei index, 6MWD, and New York Heart Association (NYHA) functional class were assessed prior to the initiation of combination therapy (baseline), at 6 months after initiation of combination therapy, and every 3 months thereafter. Two patients were followed up for 6 months only; all remaining patients reached a mean follow-up period (+/- SD) of 13.5 +/- 5.0 months (range, 9 to 22 months). 6MWD increased by 42.5 +/- 66 m at 6 months and 44.6 +/- 66 m at the last follow-up (both time points vs baseline, p < 0.001), and Tei index improved by -0.13 +/- 0.08 at 6 months and - 0.13 +/- 0.11 at the last follow-up (both time points vs baseline, p < 0.001). All patients reported subjective improvements. Nine of 16 patients exhibited improvement in NYHA functional class at 6 months. No side effects occurred that required dose adjustment or discontinuation of the study medication.
Bosentan administered to patients with progressive pulmonary hypertension receiving prostanoids resulted in an increased exercise capacity and an improved RV function. Bosentan therefore appears to be well suited for combination therapy with prostanoids in selected patients pending results of ongoing randomized trials.
肺动脉高压（PAH）是一种预后不良的进行性疾病。前列环素类药物在该疾病的医学治疗中已得到广泛应用。尽管使用了前列环素类药物，但对进行性疾病患者的治疗仍然是一项治疗挑战。在本研究中，我们研究了在现有的前列环素类药物治疗基础上加用内皮素拮抗剂波生坦对进行性肺动脉高压患者运动能力（6分钟步行距离[6MWD]）和右心室（RV）功能（Tei指数）的影响。
前瞻性、非随机、开放标签研究。
大学医院。
16例肺动脉高压患者（PAH，n = 10；其他原因导致的肺动脉高压，n = 6），患有进行性疾病，接受贝前列素（n = 3）、吸入伊洛前列素（n = 10）或静脉注射伊洛前列素（n = 3）治疗。
在至少3个月的前列环素类药物治疗不变的间隔期后，开始使用波生坦（最终剂量，125 mg，每日两次）进行联合治疗。
在联合治疗开始前（基线）、联合治疗开始后6个月以及此后每3个月评估Tei指数、6MWD和纽约心脏协会（NYHA）功能分级。2例患者仅随访6个月；所有其余患者的平均随访期（±标准差）为13.5±5.0个月（范围，9至22个月）。6MWD在6个月时增加了42.5±66 m，在最后一次随访时增加了44.6±66 m（两个时间点与基线相比，p < 0.001），Tei指数在6个月时改善了-0.13±0.08，在最后一次随访时改善了-0.13±0.11（两个时间点与基线相比，p < 0.001）。所有患者均报告主观症状有所改善。16例患者中有9例在6个月时NYHA功能分级有所改善。未出现需要调整剂量或停用研究药物的副作用。
对接受前列环素类药物治疗的进行性肺动脉高压患者给予波生坦可提高运动能力并改善RV功能。因此，在正在进行的随机试验结果出来之前，波生坦似乎非常适合与前列环素类药物联合用于特定患者的治疗。
