The National Pulmonary Hypertension Unit, Royal Free Hospital, London, UK.
Rheumatology (Oxford). 2010 Nov;49(11):2147-53. doi: 10.1093/rheumatology/keq241. Epub 2010 Jul 30.
To report outcomes in patients with CTD-pulmonary arterial hypertension (CTD-PAH) in an observational cohort treated with bosentan or sitaxentan and determine whether differences would justify a randomized, controlled multicentre study in this subpopulation.
Patients with CTD-PAH, diagnosed by right-heart catheter studies, were assigned to either bosentan or sitaxentan based on physician choice. All patients were followed up with repeat assessments and data were collected for the local registry database.
The bosentan- (n = 32) and sitaxentan- (n = 22) treated groups had comparable haemodynamic and prognostic measures at baseline. Repeat haemodynamic assessments showed reductions in pulmonary vascular resistance with bosentan (-99 dynes/s/cm(5), P < 0.01) and sitaxentan (-92 dynes/s/cm(5), P < 0.05). The 6-min walk distance improved at 3 months with sitaxentan (25 m, P < 0.05). N-terminal pro-B-type natriuretic peptide levels fell in the bosentan cohort at 6 months (-70 pmol/l, P < 0.05) and 1 year (-83 pmol/l, P < 0.01). Haemoglobin fell with both drugs (at 3 months -0.5 g/dl bosentan, P < 0.05 and -0.9 g/dl sitaxentan, P < 0.005). Calculations of the difference in treatment effect did not demonstrate superiority of either therapy. The 1-year estimated clinical worsening event rates were high: 41% sitaxentan, 62% bosentan (P = 0.142), with serious event rates of 27 and 14% (P = 0.263, log-rank test), respectively. Six patients discontinued bosentan because of transaminase elevation within the first year. Estimated 1-year survival was similar in both groups and 96% overall.
Both sitaxentan and bosentan appear effective in CTD-PAH, but the apparent additional benefit of sitaxentan reported from the open-label Sitaxentan To Relieve ImpaireD Exercise-2X study was not confirmed in this observational cohort. Although survival has improved, event rates continue to be substantial and CTD-PAH remains a therapeutic challenge.
报告在接受波生坦或西他生坦治疗的 CTD-肺动脉高压（CTD-PAH）观察队列患者中的结局，并确定在该亚组中进行随机、对照多中心研究是否存在差异。
通过右心导管检查诊断为 CTD-PAH 的患者根据医生选择被分配至波生坦或西他生坦治疗。所有患者均接受重复评估，并将数据收集到当地注册数据库中。
波生坦（n = 32）和西他生坦（n = 22）治疗组在基线时具有相似的血流动力学和预后指标。重复血流动力学评估显示波生坦（-99 达因/秒/平方厘米（5），P < 0.01）和西他生坦（-92 达因/秒/平方厘米（5），P < 0.05）均可降低肺血管阻力。西他生坦在 3 个月时 6 分钟步行距离增加（25 米，P < 0.05）。波生坦组在 6 个月时（-70 pmol/L，P < 0.05）和 1 年时（-83 pmol/L，P < 0.01）的 N 端脑利钠肽前体水平下降。两种药物均导致血红蛋白下降（波生坦组在 3 个月时下降 0.5 g/dl，P < 0.05，西他生坦组下降 0.9 g/dl，P < 0.005）。治疗效果差异的计算并未表明任何一种治疗具有优越性。1 年的估计临床恶化事件发生率较高：西他生坦组为 41%，波生坦组为 62%（P = 0.142），严重事件发生率分别为 27%和 14%（P = 0.263，对数秩检验）。6 名患者因在第一年中转氨酶升高而停用波生坦。两组的 1 年估计生存率相似，总体为 96%。
西他生坦和波生坦在 CTD-PAH 中均显示有效，但在本观察队列中，西他生坦在开放标签 Sitaxentan To Relieve ImpaireD Exercise-2X 研究中报告的明显额外益处并未得到证实。尽管生存率有所提高，但事件发生率仍然很高，CTD-PAH 仍然是一个治疗挑战。
