Front Cardiovasc Med. 2023;10:1040834.

Renal outcomes of rivaroxaban compared with warfarin in Asian patients with nonvalvular atrial fibrillation: A nationwide population-based cohort study.

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제1저자 이소령 · 교신저자 최의근

PMID 36910528 PMC9996329 DOI 10.3389/fcvm.2023.1040834 IF 3 순환기내과

소속 (7)

Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea.
Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea.
Bayer AG, Berlin, Germany.
Liverpool Centre for Cardiovascular Science, Liverpool Chest and Heart Hospital, University of Liverpool, Liverpool, United Kingdom.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Abstract

BACKGROUND Further studies are needed to expand the evidence for the association of rivaroxaban with a lower risk of adverse renal outcomes in patients with atrial fibrillation (AF) as compared with warfarin, especially in Asians.

OBJECTIVES To determine whether there are differences in adverse renal outcomes between rivaroxaban and warfarin-treated AF patients.

METHODS Using the Korean nationwide claims database partly linked to laboratory results, patients with AF who initiated warfarin or rivaroxaban from 1 January 2014 to 31 December 2017 were identified. Inverse probability of treatment weighting (IPTW) was used to balance the baseline characteristics of the two groups. The primary outcome (kidney failure) was defined as the need for maintenance dialysis or having kidney transplantation. For the exploratory analysis in a subset of patients with baseline and follow-up laboratory results, the composite of renal outcomes, including estimated glomerular filtration rate (eGFR) lower than 15 ml/min/1.73 m² at follow-up measurement, starting dialysis, or having kidney transplantation, ≥ 30% decline in eGFR, doubling of serum creatinine level, and acute kidney injury (AKI) were evaluated. The two groups were compared using Cox proportional hazards regression in the weighted population.

RESULTS We identified 30,933 warfarin users and 17,013 rivaroxaban users (51% of low dose rivaroxaban). After IPTW, the mean age was 70 years, and the mean CHA₂DS₂-VASc score was 3.9 in both groups. During a median follow-up of 0.93 (interquartile ranges 0.23-2.10) years, weighted incidence rates of kidney failure for warfarin and rivaroxaban were 0.83 and 0.32 per 100 person-years, respectively. Compared with the warfarin group, the rivaroxaban group was associated with a lower risk of kidney failure (hazard ratio [HR] 0.389, 95% confidence interval [CI] 0.300-0.499, p < 0.001). In patients with preexisting chronic kidney disease or eGFR ≤ 60 ml/min/1.73 m², rivaroxaban was more beneficial than warfarin in reducing the risk of kidney failure. For the composite of five renal outcomes in the exploratory analysis, the rivaroxaban group showed a lower risk than warfarin (HR 0.798, 95% CI 0.713-0.892, p < 0.001).

CONCLUSION Rivaroxaban was associated with lower risks of renal adverse outcomes than warfarin in Korean patients with AF.

Keywords

anticoagulationatrial fibrillationkidney failurerivaroxabanwarfarin

Figures

**Figure 1** Study enrollment flow. AF, atrial fibrillation; ESRD, end-stage renal disease; OAC, oral anticoagulant.

**Figure 2** Weighted event numbers, incidence rates, and hazard ratios for the primary and secondary outcomes between warfarin and rivaroxaban groups. Incidence rate, per 100 person-years. CI, confidence interval; GIB, gastrointestinal bleeding; ICH, intracranial hemorrhage; IPTW, inverse probability of treatment weighting; IR, incidence rate; R, rivaroxaban; W, warfarin.

**Figure 3** Subgroup analyses. CCI, Charlson comorbidity index; CI, confidence interval; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; IR, incidence rate.

**Figure 4** Exploratory analysis in patients with baseline and follow-up eGFR measurements. **(A)**. Weighted event numbers, incidence rates, and hazard ratios for five renal outcomes and composite of renal outcomes between rivaroxaban and warfarin groups **(B)**. Weighted Kaplan–Meier curves for the composite of renal outcomes between rivaroxaban and warfarin groups. Incidence rate, per 100 person-years. AKI, acute kidney injury; CI, confidence interval; Cr, creatinine; eGFR, estimated glomerular filtration rate; HR, hazard ratio; KTPL, kidney transplantation; IPTW, inverse probability of treatment weighting; IR, incidence rate; R, rivaroxaban; W, warfarin.

그림 출처: PubMed Central 공개 논문 (PMC9996329)

Conflict of interest statement

E-KC: Research grants or speaking fees from Bayer, Biosense Webster, BMS/Pfizer, Chong Kun Dang, Daiichi Sankyo, Dreamtech Co., Ltd., Jeil Pharmaceutical Co. Ltd., Medtronic, Samjinpharm, Seers Technology, and Skylabs. GL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. No fees are received personally. KA was employed by Bayer AG. This study was funded by Bayer AG. Bayer AG contributed to the design and conduct of the study; management and interpretation of the data; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication.

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