Effectiveness and safety of apixaban and warfarin in patients with new- onset atrial fibrillation after advanced chronic kidney disease or end-stage kidney disease

Ming-Ju Wu; Hsin-Hua Chen; Cheng-Hsu Chen; Shang-Feng Tsai

doi:10.1016/j.hrthm.2025.01.045

Effectiveness and safety of apixaban and warfarin in patients with new- onset atrial fibrillation after advanced chronic kidney disease or end-stage kidney disease

Heart Rhythm. 2025 May;22(5):1197-1209. doi: 10.1016/j.hrthm.2025.01.045. Epub 2025 Feb 7.

Authors

Ming-Ju Wu¹, Hsin-Hua Chen², Cheng-Hsu Chen³, Shang-Feng Tsai⁴

Affiliations

¹ Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, Chung Hsing University, Taichung, Taiwan.
² Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Institute of Biomedical Science and Rong Hsing Research Centre for Translational Medicine, Chung Hsing University, Taichung, Taiwan; Division of Clinical Informatics, Department of Digital Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
³ Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan; PhD Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁴ Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Clinical Informatics, Department of Digital Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Life Science, Tunghai University, Taichung, Taiwan. Electronic address: s881056@gmail.com.

PMID: 39923949
DOI: 10.1016/j.hrthm.2025.01.045

Abstract

Background: Limited evidence supports the use of apixaban for atrial fibrillation (AF) in patients with severe chronic kidney disease (CKD) or end-stage kidney disease (ESKD) when warfarin is often contraindicated.

Objective: Through an extensive cohort study, we attempted to compare the outcomes of apixaban and warfarin in patients within this population.

Methods: Using TriNetX data (2017-2023), we compared apixaban and warfarin in patients with chronic AF after stage 5 CKD or ESKD. Propensity score matching (PSM) and Cox multivariate analysis were applied to reduce bias. Only exclusive users were included to prevent switching influence. Subdistribution hazard ratios (SHRs) and 95% confidence intervals (CIs) for outcomes (cerebrovascular events, bleeding, and mortality) were adjusted for competing risks. Subgroup analyses considered sex, age, and dialysis status. We also compared apixaban doses to evaluate dose-related effects.

Results: After 1:1 PSM, our analysis included 1364 cases per group. The apixaban group showed significant advantages over the warfarin group in effectiveness (cerebral infarction: SHR 0.72; 95% CI 0.60-0.85; hemorrhagic stroke: SHR 0.42, 95% CI 0.28-0.63; cerebrovascular events: SHR 0.69, 95% CI 0.59-0.81), bleeding safety (gastrointestinal bleeding: SHR 0.77, 95% CI 0.61-0.97; blood transfusion: SHR 0.73, 95% CI 0.61-0.87; bleeding-related outcomes: SHR 0.75, 95% CI 0.64-0.87), and all composite outcomes (SHR 0.69, 95% CI 0.61-0.78). Subgroup analyses showed consistent improvements across gender, age, and dialysis status. Warfarin's time in therapeutic range was 44.4%. Sensitivity analysis still lacks sufficient evidence to determine whether the 5-mg or 2.5-mg dose of apixaban is superior.

Conclusion: This large cohort study highlights the lower risks of cerebrovascular events and bleeding associated with apixaban in patients with stage 5 CKD or those undergoing hemodialysis. However, the optimal dosage of apixaban requires further investigation in future studies.

Keywords: Apixaban; Atrial fibrillation; Chronic kidney disease; Dialysis; End-stage kidney disease; TriNetX; Warfarin.

Publication types

Multicenter Study

MeSH terms

Aged
Anticoagulants / administration & dosage
Atrial Fibrillation* / complications
Atrial Fibrillation* / drug therapy
Atrial Fibrillation* / etiology
Factor Xa Inhibitors / administration & dosage
Female
Follow-Up Studies
Hemorrhage / chemically induced
Humans
Kidney Failure, Chronic* / complications
Male
Middle Aged
Pyrazoles* / administration & dosage
Pyridones* / administration & dosage
Renal Insufficiency, Chronic* / complications
Retrospective Studies
Stroke* / etiology
Stroke* / prevention & control
Treatment Outcome
Warfarin* / administration & dosage
Warfarin* / adverse effects
Warfarin* / therapeutic use

Substances

apixaban
Warfarin
Pyridones
Pyrazoles
Factor Xa Inhibitors
Anticoagulants