Front Cardiovasc Med. 2022;9:885548.

Efficacy and Safety of Oral Anticoagulants for Atrial Fibrillation Patients With Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

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제1저자 이태민, 이소령 · 교신저자 최의근

PMID 35757349 PMC9226375 DOI 10.3389/fcvm.2022.885548 IF 3 순환기내과

소속 (4)

Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.
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 Data on different direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with renal impairment are insufficient. We aimed to perform pairwise and network meta-analysis comparing oral anticoagulants (OACs) in AF patients with renal impairment, including advanced chronic kidney disease (CKD) with creatinine clearance <30 mL/min.

METHODS PubMed, Embase, Cochrane Database, and references of related articles were searched up to April 2021. We included randomized trials and non-randomized studies using propensity-score or multivariable-model adjustments that compared clinical outcomes among OACs. Hazard ratios (HRs) for stroke or thromboembolism, major bleeding, and all-cause death were pooled using random-effects model.

RESULTS From 19 studies, 124,628 patients were included. In patients with AF and CKD, DOACs presented significantly lower risks of stroke or thromboembolism [HR_pooled = 0.78, 95% confidence interval (CI) = 0.73-0.85, I² = 16.6%] and major bleeding [HR_pooled = 0.76 (0.64-0.89), I² = 85.7%] when compared with warfarin, regardless of the severity of renal impairment. Results were consistent in advanced CKD patients for stroke or thromboembolism [HR_pooled = 0.60 (0.43-0.85), I² = 0.0%] and major bleeding [HR_pooled = 0.74 (0.59-0.93), I² = 30.4%]. In the network meta-analysis, edoxaban and apixaban presented the highest rank probability to reduce the risk of stroke or thromboembolism (edoxaban, P-score = 94.5%) and major bleeding (apixaban, P-score = 95.8%), respectively. Apixaban remained the safest OAC with the highest rank probability for major bleeding (P-score = 96.9%) in patients with advanced CKD.

CONCLUSION DOACs, particularly apixaban and edoxaban, presented superior efficacy and safety than warfarin in AF patients with CKD. Apixaban was associated with the lowest risk of major bleeding among OACs for patients with advanced CKD.

SYSTEMATIC REVIEW REGISTRATION [PROSPERO], identifier [CRD42021241718].

Keywords

anticoagulationatrial fibrillationchronic kidney diseasedirect oral anticoagulantmeta-analysis

Figures

**Figure 1** Study flow. Flow of search and study selection are presented.

**Figure 2** Comparison of pooled treatment effects of oral anticoagulants on clinical outcomes in atrial fibrillation patients with concomitant chronic kidney disease. Pooled HR and 95% CI, I² and P-value for heterogeneity are presented for stroke or thromboembolism, major bleeding, and all-cause death according to the severity of renal impairment. CI, confidence interval; CKD, chronic kidney disease; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; HR, hazard ratio; NA, not applicable; PS, propensity-score; RCT, randomized controlled trial.

**Figure 3** Subgroup analysis for stroke or thromboembolism and major bleeding. Subgroup analysis across various subgroups are presented. CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; CI, confidence interval; CKD, chronic kidney disease; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; HR, hazard ratio; NA, not applicable; PS, propensity-score; RCT, randomized controlled trial.

**Figure 4** Results of network meta-analysis comparing safety and efficacy of oral anticoagulants in all CKD and advanced CKD patients. Results of frequentist network meta-analysis for all CKD patients with CrCl <60 mL/min, **(A)** network plot **(B)** forest plot, and for advanced CKD patients with CrCl <30 mL/min, **(C)** network plot, and **(D)** forest plot, are presented. ref., reference; CI, confidence interval; CKD, chronic kidney disease; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; HR, hazard ratio; NA, not applicable; PS, propensity-score; RCT, randomized controlled trial.

**Figure 5** Clustered ranking plots of oral anticoagulants for stroke or thromboembolism and major bleeding. P-score based rankings of various oral anticoagulants for stroke or thromboembolism and major bleeding are plotted. **(A)** All CKD with CrCl <60 mL/min and **(B)** advanced CKD with CrCl <30 mL/min. CI, confidence interval; CKD, chronic kidney disease; CrCl, creatinine clearance; DOAC, direct oral anticoagulant; HR, hazard ratio; NA, not applicable; PS, propensity-score; RCT, randomized controlled trial.

그림 출처: PubMed Central 공개 논문 (PMC9226375)

Conflict of interest statement

E-KC: Research grants or speaking fees from Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daiichi-Sankyo, Dreamtech Co., Ltd., Medtronic, Samjinpharm, Sanofi-Aventis, Seers Technology, Skylabs, and Yuhan; GL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim and Daiichi-Sankyo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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