Limited evidence exists regarding the use of factor Xa inhibitors for the treatment of venous thromboembolism (VTE) in patients with severe renal impairment. Notably, these patients were excluded from clinical trials.The goal of this study was to examine the safety and effectiveness of apixaban versus warfarin for the treatment of acute VTE in patients with severe renal impairment.This retrospective cohort study was conducted across 36 Ascension Health sites between 2014 and 2024. Adult patients receiving apixaban or warfarin for VTE treatment with severe renal impairment were included. The primary outcome was time to composite bleeding event within six months.This study included 1200 patients receiving apixaban and 600 patients receiving warfarin. Overall, 23.4% of the study population had ESRD requiring renal replacement therapy. Among patients not requiring renal replacement therapy, stage IV CKD was most common (43.8%). No difference in time to composite bleeding events (HR 1.01
95% CI 0.74-1.38, p = 0.97) or recurrent VTE (HR 1.24
95% CI 0.70-2.18, p = 0.46) were noted after controlling for confounders. Furthermore, major bleeding (4.7% vs. 7.5%, p = 0.43) and clinically-relevant non-major bleeding (4.3% vs. 6.2%, p = 0.08) were similar between groups. Apixaban was associated with a significantly reduced incidence of anticoagulation-related ED admission (6.8% vs. 9.8%, p = 0.02) compared to warfarin. Anticoagulation-related readmission (7.4% vs. 8%, p = 0.66) and time to all-cause mortality (5.2% vs. 6.2%, p = 0.38) were similar between groups.No differences in safety or effectiveness were noted between apixaban and warfarin, providing encouraging evidence to support the use of apixaban for treatment of acute VTE in patients with severe renal impairment.