Abstract

Atrial fibrillation (AF) is the most common arrhythmia in chronic kidney disease (CKD), with a close bidirectional relationship between the two entities. The presence of CKD in AF increases the risk of thromboembolic events, mortality and bleeding. Vitamin K antagonists (VKA) have been the mainstay of treatment for the prevention of thromboembolic events in AF until recently, with confirmed benefits in AF patients with stage 3 CKD. However, the risk-benefit profile of VKA in patients with AF and stages 4–5 CKD is controversial due to the lack of evidence from randomized controlled trials. Treatment with VKA in CKD patients has been associated with conditions such as poorer anticoagulation quality, increased risk of bleeding, faster progression of vascular/valvular calcification and higher risk of calciphylaxis. Direct oral anticoagulants (DOACs) have shown equal or greater efficacy in stroke/systemic embolism prevention, and a better safety profile than VKA in post-hoc analysis of the pivotal randomized controlled trials in patients with non-valvular AF and stage 3 CKD, yet evidence of its risk-benefit profile in more advanced stages of CKD is scarce. Observational studies associate DOACs with a good safety/effectiveness profile compared to VKA in non-dialysis CKD patients. Further, DOACs have been associated with a lower risk of acute kidney injury and CKD development/progression than VKA. This narrative review summarizes the evidence of the efficacy and safety of warfarin and DOACs in patients with AF at different CKD stages, as well as their effects on renal function, vascular/valvular calcification and bone health.

Highlights

  • Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of stroke or systemic embolism (S/SE) [1]

  • The relationship between AF and Chronic kidney disease (CKD) is bidirectional: AF is associated with an increased risk of CKD [reduced glomerular filtration rate (GFR) or albuminuria], while CKD is linked to increased incidence/prevalence of AF [6,7,8,9]

  • CKD Development and Progression Post-hoc analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET) [73] and Randomized Evaluation of Long-Term Anticoagulant Therapy with Dabigatran etexilate (RE-LY) [96] trials suggest that Direct oral anticoagulants (DOACs) have a more beneficial effect on renal function decline than warfarin, which has been confirmed in multiple observational studies [76, 94, 95, 97,98,99]

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Summary

Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of stroke or systemic embolism (S/SE) [1]. In a recent meta-analysis in ESKD patients with AF, DOACs showed comparable effectiveness and safety to VKA, while OAT vs no anticoagulation was associated with a higher risk of IS/SE and a similar risk of major bleeding [67].

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