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Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials

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Abstract

Background

In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown.

Purpose

To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis.

Methods

We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics.

Results

Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18–0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17–1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45–1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66–2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77–1.24; p = 0.84; I2 = 16%).

Conclusion

This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.

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Abbreviations

ACC/AHA:

American College of Cardiology, American Heart Association

AF:

Atrial Fibrillation

CKD:

Chronic Kidney Disease

DOAC:

Direct Oral Anticoagulant

HD:

Hemodialysis

HF:

Heart Failure

ISTH:

International Society on Thrombosis and Hemostasis

OAC:

Oral Anticoagulant

VKA:

Vitamin K Antagonist

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Health Sciences, Federal University of Rio Grande do Norte, Natal, Brazil

    Larissa A. de Lucena, Ana K. C. Souza & Caroliny H. A. Silva

  2. Department of Medicine, State University of Região Tocantina do Maranhão, Department of Medicine, Imperatriz, Brazil

    Marcos A. A. Freitas

  3. Department of Medicine, State University of Piauí, Teresina, Brazil

    Janine M. F. Watanabe

  4. Division of Nephrology, University Hospital Onofre Lopes, Natal, Brazil

    Felipe L. Guedes

  5. Department of Integrated Medicine, Federal University of Rio Grande do Norte, Nilo Peçanha Avenue, 620, 3rd underground – Petroópolis, Natal, 59012-300, Brazil

    Jose B. Almeida & Rodrigo A. de Oliveira

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  1. Larissa A. de Lucena
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Contributions

Research idea and study design: Larissa A. de Lucena and Rodrigo A. de Oliveira; data acquisition: Larissa A. de Lucena, Marcos A. A. Freitas, Ana K. C. Souza, Caroliny H. A. Silva, Janine M. F. Watanabe; data analysis/interpretation: Larissa A. de Lucena, Ana K. C. Souza, Caroliny H. (A) Silva, Janine M. F. Watanabe, Felipe L. Guedes, Jose (B) Almeida; statistical analysis: Larissa A. de Lucena1, Marcos A. A. Freitas; supervision or mentorship: Rodrigo (A) de Oliveira, Felipe L. Guedes, Jose (B) Almeida. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate.

Corresponding author

Correspondence to Rodrigo A. de Oliveira.

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Ethical approval was not required because this study retrieved and synthesized data from previously published studies.

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Online Resource 1: Supplemental Tables 1 - Major bleeding definitions

11239_2023_2945_MOESM2_ESM.png

Online Resource 2: Supplemental Fig. 1 - a: Stroke was not significantly different in the subgroup analysis (P = 0.16). b: Ischemic stroke was similar between DOAC and VKA in the subgroup analysis (P = 0.17). CI = confidence interval; M-H = Mantel-Haenszel method; DOAC = direct oral anticoagulant; VKA = vitamin K antagonist

11239_2023_2945_MOESM3_ESM.png

Online Resource 3: Supplemental Fig. 2 - a: The incidence of major bleeding in the subgroup analysis shows no differences (P = 0.48). b: The groups did not differ in all-cause mortality (P = 0.96). c: The CV death was not significantly different between DOACs and VKAs in this subgroup analysis (P = 0.36). CI = confidence interval; M-H = Mantel-Haenszel method; DOAC = direct oral anticoagulant; VKA = vitamin K antagonist

Online Resource 4: Supplemental Tables 2 - Risk of bias summary for randomized studies (RoB 2)

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de Lucena, L.A., Freitas, M.A.A., Souza, A.K.C. et al. Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials. J Thromb Thrombolysis 57, 381–389 (2024). https://doi.org/10.1007/s11239-023-02945-0

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