Scoping review of apixaban and rivaroxaban dosing for atrial fibrillation and venous thromboembolism in advanced chronic kidney disease.

INTRODUCTION

Individuals with advanced chronic kidney disease (CKD) have elevated risks for stroke, venous thromboembolism (VTE), and bleeding, yet their exclusion from major trials leaves uncertainty about dosing of apixaban and rivaroxaban.

AIM: To map existing evidence on apixaban and rivaroxaban dosing practices and associated clinical outcomes in patients with advanced CKD, predominantly not receiving dialysis, treated for atrial fibrillation (AF) and/or venous thromboembolism (VTE), and to identify knowledge gaps in this area.

METHOD: A scoping review was conducted following the Arksey and O'Malley framework and reported per PRISMA-ScR guidelines. The search, developed with a medical librarian, was conducted in MEDLINE, Embase, Cochrane, and CINAHL through May 7, 2025. Duplicates were removed, and records managed in Covidence. Two reviewers independently screened titles, abstracts, and full texts. We included studies of apixaban or rivaroxaban dosing in adults with advanced CKD (mostly non-dialysis) with AF or VTE reporting thromboembolic or major bleeding outcomes. Non-English articles and publication types (e.g., abstracts, case series, editorials) were excluded. Data was extracted using a structured form and summarized to address the study aim.

RESULTS

Thirty-four studies were identified: seven VTE, six combined AF/VTE, and 21 AF. Standard-dose apixaban and rivaroxaban were more commonly used and associated with lower, though non-significant, rates of recurrent VTE and major bleeding compared to warfarin. In apixaban groups, standard-dose 5 mg BID had fewer VTE events than the 2.5 mg BID dose but more major bleeding events which were also not statistically significant. In AF studies, both standard and reduced-dose apixaban (5 mg BID and 2.5 mg BID), and reduced-dose rivaroxaban (15 mg daily), significantly reduced major bleeding risk versus warfarin. Stroke reductions were not consistently significant but trended lower with apixaban and rivaroxaban compared to warfarin. In the only AF study comparing apixaban and rivaroxaban, both doses of rivaroxaban (20 mg or 15 mg daily) had higher bleeding rates than apixaban. One of four AF studies showed higher bleeding with standard versus reduced-dose apixaban.

CONCLUSION

This review summarizes apixaban and rivaroxaban dosing for AF/VTE in advanced CKD, revealing gaps such as limited dose-comparison studies, heterogeneous outcomes and sparse data in non-dialysis. Robust trials are urgently needed.