Advanced Lung Disease and Transplant Clinic, Inova Fairfax Hospital, Falls Church, VA.
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.
Chest. 2021 Apr;159(4):1507-1516. doi: 10.1016/j.chest.2020.10.019. Epub 2020 Oct 16.
Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes.
The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry.
An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models.
Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC.
The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD.
凝血系统的异常与间质性肺病（ILD）的发病机制有关。抗凝剂已被提议作为ILD 的潜在治疗方法；然而，由于死亡率升高，一项检查华法林治疗特发性肺纤维化（IPF）的随机对照试验提前终止。这导致一些人推测华法林在ILD 中可能特别有害，而使用直接口服抗凝剂（DOAC）可能会带来更好的结果。
本研究的目的是通过分析肺纤维化基金会患者登记处，阐明 ILD 患者抗凝与结局之间的关系。
对肺纤维化基金会患者登记处的所有患者进行了分析。患者分为三组：无抗凝治疗、使用 DOAC 或华法林。使用 Kaplan-Meier 曲线和 Cox 比例风险模型分析生存情况。
在纳入分析的 1911 名患者中，有 174 名（9.1%）接受了抗凝治疗；93 名（4.9%）使用 DOAC，81 名（4.2%）使用华法林。使用 DOAC 的患者死亡或移植的风险增加了两倍；而使用华法林的患者，其风险增加了两倍半以上。在调整混杂变量后，DOAC 并不增加死亡率。然而，即使在调整后，使用抗凝药物华法林的患者死亡风险仍然增加。在 IPF 患者中，华法林与无移植生存率降低相关，但 DOAC 则不然。接受华法林治疗的患者与接受 DOAC 治疗的患者之间的生存没有统计学上的显著差异。
在 ILD 患者中，抗凝治疗与死亡或移植风险增加相关，无论在 IPF 患者还是非 IPF 患者中均如此。需要进一步研究以确定华法林和 DOAC 在 ILD 患者中是否具有不同的安全性特征。
