Bosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia
Bosentan in Pulmonary Hypertension Associated with Fibrotic Idiopathic Interstitial Pneumonia
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DOI：
10.1164/rccm.201403-0446oc
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发表时间：
2014-07-15
影响因子：
24.7
通讯作者：
Wort, Stephen J.
中科院分区：
文献类型：
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作者：
Corte, Tamera J.;Keir, Gregory J.;Wort, Stephen J.
基本原理：纤维化特发性间质性肺炎相关的肺动脉高压（PH）（TIP;特发性肺纤维化和非特异性间质性肺炎）赋予重要的额外发病率和死亡率：目的：评价双重内皮素-1受体拮抗剂波生坦在该患者组中的安全性和临床疗效。在一项随机、双盲、安慰剂对照研究中，60例经右心导管证实的纤维化IIP和PH患者以2：1的比例随机接受波生坦（n = 40）或安慰剂（n = 20）治疗。主要研究终点是16周内肺血管阻力指数（PVRi）较基线下降20%或以上。（42名男子;平均年龄66.6 ± 9.2岁），平均肺动脉压36.0本研究招募了（+/- 8.9）mm Hg、PVRi 13.0（6.7）Wood Units/m2和降低的心脏指数2.21（+/- 0.5）Ilmin/m2的受试者。考虑到死亡和退出，39例患者的配对右心导管数据可用于分析（波生坦= 25，安慰剂= 14）。主要结局无差异，7例（28.0%）接受波生坦治疗的患者和4例（28.6%）接受安慰剂治疗的患者在16周时PVRi降低≥ 20%（P = 0.97）。没有任何变化。在16周时两组之间的功能容量或症状，在严重不良事件或死亡率方面也没有任何差异（每组3例死亡）。结论：本研究表明，在16周内，波生坦组和安慰剂组之间的侵入性肺血流动力学、功能容量或症状没有差异。我们的数据不支持在PH和纤维化TIP患者中使用双重内皮素-1受体拮抗剂波生坦。
Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (TIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality:Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group.Methods: In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks.Measurements and Main Results: Sixty patients (42 men; mean age, 66.6 +/- 9.2 yr), with a mean pulmonary artery pressure of 36.0 (+/- 8.9) mm Hg, PVRi 13.0 (6.7) Wood Units/m2 and reduced cardiac index of 2.21 ( +/- 0.5) Ilmin/m(2) were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change in. functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group).Conclusions: This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic TIP.