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Efficacy and Safety of Direct Oral Anticoagulants vs Warfarin in Patients with Chronic Kidney Disease and Dialysis Patients: A Systematic Review and Meta-Analysis

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Abstract

Background and Objective

Systematic reviews and meta-analyses of direct oral anticoagulants (DOACs) for patients with chronic kidney disease (CKD) or dialysis patients are lacking. We aimed to compare the efficacy and safety of DOACs and warfarin in patients with CKD requiring anticoagulation therapy.

Methods

We performed a systematic review and meta-analysis of six randomized controlled trials and 19 observational studies, with the inclusion criteria being a comparative study between DOACs and warfarin in patients with CKD or dialysis patients from database inception until August 2020. The efficacy outcomes were stroke, systemic embolism (SE), or venous thromboembolism (VTE), and the safety outcome was major bleeding.

Results

Compared with warfarin, DOACs significantly reduced the risk of stroke/SE/VTE by 22% (hazard ratio [HR] = 0.78, 95% confidence interval [CI] 0.64–0.95) and major bleeding by 17% (HR = 0.83, 95% CI 0.71–0.97). On comparing factor Xa inhibitors and dabigatran with warfarin separately, factor Xa inhibitors significantly reduced the risk of stroke/SE/VTE (HR = 0.78, 95% CI 0.62–0.98) and major bleeding (HR = 0.76, 95% CI 0.64–0.91) overall in patients. Comparing each DOACs with warfarin separately, apixaban was associated with a significantly better risk reduction of stroke/SE/VTE (25% risk reduction) and major bleeding (35% risk reduction) than warfarin. Compared with warfarin, DOACs significantly reduced the risk of stroke, SE, or VTE by 19% (HR = 0.81, 95% CI 0.68–0.97) in patients with CKD stage 3 and significantly lowered the risk of major bleeding by 31% (HR = 0.69, 95% CI 0.56–0.85) in patients with CKD stages 4–5.

Conclusions

In pooled, analyzed randomized controlled trials and observational studies, DOACs were associated with better efficacy in early CKD, as well as similar efficacy and safety outcomes to warfarin in patients with CKD stages 4–5 or dialysis patients. The results of patients with CKD stages 4–5 and dialysis patients were from observational studies. Well-designed randomized controlled trials focused on DOAC use in patients with CKD and dialysis patients are needed.

PROSPERO register number: CRD42020150599, 6 February, 2020.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

    Hsin-Yu Chen, Shih-Hsiang Ou, Chien-Wei Huang, Po-Tsang Lee & Kang-Ju Chou

  2. Department of Pharmacy, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan

    Yi-Chia Su

  3. Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan

    Pei-Chin Lin

  4. School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Hsin-Yu Chen, Shih-Hsiang Ou, Chien-Wei Huang, Po-Tsang Lee & Kang-Ju Chou

  5. Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng-Kung University, Tainan, Taiwan

    Yi-Chia Su

  6. Department of Pharmacy, School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

    Pei-Chin Lin

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  1. Hsin-Yu Chen
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Correspondence to Yi-Chia Su.

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Funding

This work was supported by Kaohsiung Veterans General Hospital (Grant Number: VGHKS108-D08-2).

Conflict of interest

Hsin-Yu Chen, Shih-Hsiang Ou, Chien-Wei Huang, Po-Tsang Lee, Kang-Ju Chou, Pei-Chin Lin, and Yi-Chia Su have no conflicts of interest that are directly relevant to the content of this article.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Author contributions

H-YC was involved in the design of the study, extraction of the data, statistical analyses, interpretation of the results, and drafting and revising the manuscript. Y-CS was involved in the design of the study, extraction of the data, and revising the manuscript. S-HO and C-WH were involved in the interpretation of the results and revising the manuscript. P-TL was involved in the design of the study, interpretation of the results, and revising the manuscript. K-JC was involved in the interpretation of the results and revising the manuscript. P-CL was involved in the design of the study, interpretation of the results, and drafting and revising the manuscript. P-CL is the guarantor of the manuscript. She accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. P-CL attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

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Chen, HY., Ou, SH., Huang, CW. et al. Efficacy and Safety of Direct Oral Anticoagulants vs Warfarin in Patients with Chronic Kidney Disease and Dialysis Patients: A Systematic Review and Meta-Analysis. Clin Drug Investig 41, 341–351 (2021). https://doi.org/10.1007/s40261-021-01016-7

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