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Anticoagulants in atrial fibrillation patients with chronic kidney disease

Nature Reviews Nephrology volume 8, pages 569–578 (2012)Cite this article

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Abstract

Atrial fibrillation is an important cause of preventable, disabling stroke and is particularly frequent in patients with chronic kidney disease (CKD). Stage 3 CKD is an independent risk factor for stroke in patients with atrial fibrillation. Warfarin anticoagulation is efficacious for stroke prevention in atrial fibrillation patients with stage 3 CKD, but recent observational studies have challenged its value for patients with end-stage renal disease and atrial fibrillation. Novel oral anticoagulants such as dabigatran, apixaban and rivaroxaban are at least as efficacious as warfarin with reduced risks of intracranial haemorrhage. However, all these agents undergo renal clearance to varying degrees, and hence dosing, efficacy, and safety require special consideration in patients with CKD. Overall, the novel oral anticoagulants have performed well in randomized trials of patients with stage 3 CKD, with similar efficacy and safety profiles as for patients without CKD, albeit requiring dosing modifications. The required period of discontinuation of novel oral anticoagulants before elective surgery is longer for patients with CKD owing to their reduced renal clearance. Although much remains to be learned about the optimal use of these new agents in patients with CKD, they are attractive anticoagulation options that are likely to replace warfarin in coming years.

Key Points

  • Atrial fibrillation is particularly frequent in patients with chronic kidney disease (CKD)

  • Stage 3 CKD is an independent risk factor for stroke in patients with atrial fibrillation

  • Recent observational studies have challenged the value of warfarin anticoagulation for patients with end-stage renal disease and atrial fibrillation

  • Novel oral anticoagulants such as dabigatran, apixaban and rivaroxaban are noninferior or superior to warfarin, with reduced risks of intracranial haemorrhage

  • In randomized trials to date, the novel oral anticoagulants have performed well in patients with stage 3 CKD, with similar efficacy and safety profiles as for patients without CKD, although dosing modifications are required

  • The required period of discontinuation of novel oral anticoagulants before elective surgery is longer for patients with CKD than for patients without renal dysfunction

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Figure 1: Relative risk reductions in stroke or systemic embolism and major haemorrhage by novel oral anticoagulants versus warfarin in patients with moderate CKD.9,12,25
Figure 2: Hazard ratios for subgroups of patients with stage 3 CKD from two randomized trials comparing anticoagulation with aspirin.29,30
Figure 3: Hazard ratios for subgroups of patients with stage 3 CKD (estimated creatinine clearances 30–49 ml/min or 25–50 ml/min for apixaban) from randomized trials comparing novel oral anticoagulants with warfarin for the primary outcome of stroke and systemic embolism.9,12,25

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Authors and Affiliations

  1. Division of Neurology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, ON, Canada

    Robert G. Hart

  2. Division of Hematology and Thromboembolism, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, ON, Canada

    John W. Eikelboom

  3. Division of Nephrology, Department of Medicine, McMaster University, 1280 Main Street West, Hamilton, L8S 4L8, ON, Canada

    Alistair J. Ingram

  4. Division of Cardiology, Department of Medicine, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, 55415, USA, MN

    Charles A. Herzog

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All authors contributed equally to discussion of content for the article, researching data to include in the manuscript, and reviewing and editing of the manuscript before submission. R. G. Hart and J. W. Eikelboom wrote the manuscript.

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Correspondence to Robert G. Hart.

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Competing interests

R. G. Hart has worked as a consultant for Boehringer Ingelheim and received grant/research support from Bayer Pharmaceuticals and Bristol-Myers Squibb. J. W. Eikelboom has received grant/research support from Bayer Pharmaceuticals, Boehringer Ingelheim and Bristol-Myers Squibb. C. A. Herzog has received research support from and has equity interest (<$10,000) in Johnson and Johnson. A. J. Ingram declares no competing interests.

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Hart, R., Eikelboom, J., Ingram, A. et al. Anticoagulants in atrial fibrillation patients with chronic kidney disease. Nat Rev Nephrol 8, 569–578 (2012). https://doi.org/10.1038/nrneph.2012.160

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