Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin

Oluwadolapo D Lawal; Herbert D Aronow; Anne L Hume; Fisayomi Shobayo; Kelly L Matson; Marilyn Barbour; Yichi Zhang; Xuerong Wen

doi:10.1016/j.rpth.2023.102293

Venous thromboembolism, chronic liver disease and anticoagulant choice: effectiveness and safety of direct oral anticoagulants versus warfarin

Res Pract Thromb Haemost. 2023 Dec 9;8(1):102293. doi: 10.1016/j.rpth.2023.102293. eCollection 2024 Jan.

Authors

Oluwadolapo D Lawal¹, Herbert D Aronow^{2

3}, Anne L Hume¹, Fisayomi Shobayo⁴, Kelly L Matson¹, Marilyn Barbour¹, Yichi Zhang⁵, Xuerong Wen¹

Affiliations

¹ Department of Pharmacy Practice, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
² Lifespan Cardiovascular Institute, Providence, Rhode Island, USA.
³ Division of Cardiology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁴ Department of Cardiology, University of Texas Health Science Center, Houston, Texas, USA.
⁵ Department of Computer Sciences and Statistics, University of Rhode Island, Kingston, Rhode Island, USA.

Abstract

Background: Little to no data exist to guide treatment decision in patients with venous thromboembolism (VTE) and chronic liver disease.

Objectives: To assess the effectiveness and safety of direct oral anticoagulants (DOACs)-individually and as a class-vs warfarin and between 2 DOACs in patients with acute VTE and chronic liver disease.

Methods: We conducted a retrospective, US claims-based, propensity score-matched cohort study in adults with acute VTE and chronic liver disease who had newly initiated oral anticoagulants between 2011 and 2017. The primary outcome was a composite of hospitalization for recurrent VTE and hospitalization for major bleeding.

Results: The cohorts included 2361 DOAC-warfarin, 895 apixaban-warfarin, 2161 rivaroxaban-warfarin, and 895 apixaban-rivaroxaban matched pairs. Lower risk of the primary outcome was seen with DOACs (hazard ratio [HR], 0.72; 95% CI, 0.61-0.85), apixaban (HR, 0.48; 95% CI, 0.35-0.66) or rivaroxaban (HR, 0.73; 95% CI, 0.61-0.88) vs warfarin but not apixaban-rivaroxaban (HR, 0.68; 95% CI, 0.43-1.08). The HRs of hospitalization for major bleeding were 0.69 (95% CI, 0.57-0.84) for DOAC-warfarin, 0.43 (95% CI, 0.30-0.63) for apixaban-warfarin, 0.72 (95% CI, 0.58-0.89) for rivaroxaban-warfarin, and 0.60 (95% CI, 0.35-1.06) for apixaban-rivaroxaban. Recurrent VTE risk was lower with apixaban (HR, 0.47; 95% CI, 0.26-0.86), but not DOACs (HR, 0.81; 95% CI, 0.59-1.12) or rivaroxaban vs warfarin (HR, 0.81; 95% CI, 0.57-1.14) or apixaban-rivaroxaban (HR, 0.92; 95% CI, 0.42-2.02).

Conclusion: While the magnitude of clinical benefit varied across individual DOACs, in adults with acute VTE and chronic liver disease, oral factor Xa inhibitors (as a class or individually) were associated with lower risk of recurrent VTE and major bleeding.

Keywords: anticoagulants; factor Xa inhibitors; liver diseases; venous thromboembolism; warfarin.