University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637-6076, USA.
Am J Respir Crit Care Med. 2012 Jul 1;186(1):88-95. doi: 10.1164/rccm.201202-0314OC. Epub 2012 May 3.
Animal and human studies support the importance of the coagulation cascade in pulmonary fibrosis.
In a cohort of subjects with progressive idiopathic pulmonary fibrosis (IPF), we tested the hypothesis that treatment with warfarin at recognized therapeutic doses would reduce rates of mortality, hospitalization, and declines in FVC.
This was a double-blind, randomized, placebo-controlled trial of warfarin targeting an international normalized ratio of 2.0 to 3.0 in patients with IPF. Subjects were randomized in a 1:1 ratio to warfarin or matching placebo for a planned treatment period of 48 weeks. International normalized ratios were monitored using encrypted home point-of-care devices that allowed blinding of study therapy.
The primary outcome measure was the composite outcome of time to death, hospitalization (nonbleeding, nonelective), or a 10% or greater absolute decline in FVC. Due to a low probability of benefit and an increase in mortality observed in the subjects randomized to warfarin (14 warfarin versus 3 placebo deaths; P = 0.005) an independent Data and Safety Monitoring Board recommended stopping the study after 145 of the planned 256 subjects were enrolled (72 warfarin, 73 placebo). The mean follow-up was 28 weeks.
This study did not show a benefit for warfarin in the treatment of patients with progressive IPF. Treatment with warfarin was associated with an increased risk of mortality in an IPF population who lacked other indications for anticoagulation.
动物和人体研究均支持凝血级联反应在肺纤维化中的重要性。
在进展性特发性肺纤维化（IPF）患者队列中，我们检验了以下假说，即在公认的治疗剂量下应用华法林治疗可降低死亡率、住院率和 FVC 下降率。
这是一项针对 IPF 患者的华法林双盲、随机、安慰剂对照试验，目标 INR 范围为 2.0 至 3.0。患者以 1:1 的比例随机分配至华法林组或匹配安慰剂组，计划治疗期为 48 周。使用加密的家庭即时检测设备监测 INR，该设备可实现研究治疗的盲法。
主要终点是死亡、住院（非出血性、非择期）或 FVC 绝对下降 10%或更多的复合终点。由于观察到华法林组发生获益可能性低和死亡率增加（14 例华法林与 3 例安慰剂死亡；P=0.005），一个独立的数据和安全监测委员会建议在计划入组的 256 例患者中的 145 例入组后（72 例华法林，73 例安慰剂）停止研究。中位随访时间为 28 周。
本研究未显示华法林在治疗进展性 IPF 患者中有益。在缺乏其他抗凝指征的 IPF 人群中，华法林治疗与死亡率增加相关。
