The optimal approach to prevent stroke and systemic embolism in patients with advanced chronic kidney disease (CKD) and atrial fibrillation remains unresolved. We conducted a narrative review to explore areas of uncertainty and opportunities for future research. First, the relationship between atrial fibrillation and stroke is more complex in patients with advanced CKD than in the general population. The currently employed risk stratification tools do not adequately discriminate between patients deriving a net benefit and those suffering a net harm from oral anticoagulation. Anticoagulation initiation should probably be more restrictive than is currently advocated by official guidelines. Recent evidence reveals that the superior benefit-risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) vs vitamin K antagonists (VKAs) observed in the general population and in moderate CKD can be extended to advanced CKD. The NOACs yield better protection against stroke, cause less major bleeding, are associated with less acute kidney injury and a slower decline of CKD, and are associated with a lower incidence of cardiovascular events than VKAs. The VKAs may be harmful in CKD patients, in particular in patients with a high bleeding risk and labile international normalized ratio. The better safety and efficacy of NOACs as opposed to VKAs may be particularly evident in advanced CKD as a result of better on-target anticoagulation with NOACs, harmful off-target vascular effects of VKAs, and beneficial off-target vascular effects of NOACs. The intrinsic vasculoprotective effects of NOACs are supported by animal experimental evidence as well as by findings of large clinical trials and may result in use of NOACs beyond their anticoagulant properties.
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