Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

Abstract Background 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 control trial examining warfarin as a treatment for IPF was terminated early for harm. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) may result in superior outcomes. Research Question We sought to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation (PFF) registry. Study Design and Methods: An analysis of all patients in the PFF registry was performed. Patients were stratified into three groups: no anticoagulation (AC), DOAC use, or warfarin use. Survival was analyzed using both Kaplan Meier curves and Cox proportional hazards models. Results Of 1,911 patients included in the analysis, 174 (9.1%) were anticoagulated, 93 (4.9%) with DOACs, and 81 (4.2%) with warfarin. There was a two-fold increased risk of death or transplant for patients receiving DOACS, while for warfarin this was over a two and half times greater risk. DOACs were not associated with an increased risk of mortality after adjustment for confounding variables. However, even after adjustment, patients anticoagulated with 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. Interpretation 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 ILD patients. (292 words)