Oral Factor Xa Inhibitors versus Warfarin for the Treatment of Venous Thromboembolism in Advanced Chronic Kidney Disease

Abstract

Introduction. Warfarin remains the preferred oral anticoagulant for the treatment of venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD). Although the direct oral anticoagulants (DOACs) have become preferred for treatment of VTE in the general population, patients with advanced CKD were excluded from the landmark trials. Postmarketing, safety data have demonstrated oral factor Xa inhibitors (OFXais) such as apixaban and rivaroxaban to be alternatives to warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, it remains unknown if these safety data can be extrapolated to the treatment of VTE and CKD. Methods. A retrospective cohort study from January 2013 to October 2019 was performed at NYU Langone Health. All adult patients with CKD stage 4 or greater, treated with anticoagulation for VTE, were screened. The primary outcome was tolerability of anticoagulant therapy at 3 months, defined as a composite of bleeding, thromboembolic events, and/or discontinuation rates. The secondary outcomes included bleeding, discontinuations, and recurrent thromboembolism. Results. There were 56 patients evaluated, of which 39 (70%) received warfarin and 17 (30%) received an OFXai (apixaban or rivaroxaban). Tolerability at 3 months was assessed in 48/56 patients (86%). A total of 34/48 (71%) patients tolerated anticoagulation at 3 months, 12 (80%) in the OFXai arm, and 22 (67%) in the warfarin arm ( $p=0.498$ ). There were 10/48 (21%) patients that experienced any bleeding events within 3 months, 7 on warfarin, and 3 on apixaban. Recurrence of thromboembolism within 3 months occurred in 3 patients on warfarin, with no recurrence in the OFXai arm. Discussion. OFXais were better tolerated compared to warfarin for the treatment of VTE in CKD, with lower rates of bleeding, discontinuations, and recurrent thromboembolism in a small cohort. Future prospective studies are necessary to confirm these findings.