Which Anticoagulants Should Be Used for Stroke Prevention in Non-Valvular Atrial Fibrillation and Severe Chronic Kidney Disease?

Philip A. Kalra; Alexandru Burlacu; Charles J. Ferro; Adrian Covic

Disclosures

Curr Opin Nephrol Hypertens. 2018;27(6):420-425. 

In This Article

Abstract and Introduction

Abstract

Purpose of review: Non-valvular atrial fibrillation is common in patients with severe chronic kidney disease (CKD) and historically patients have been treated with vitamin K antagonists (VKA). However, these agents have questionable efficacy and are associated with increased bleeding risk. Non-vitamin K oral anticoagulants (NOAC) have advantages over VKA in early stage CKD. In this review, we sought to establish evidence for best practice in patients with severe CKD (creatinine clearance <30 ml/min including dialysis patients) and nonvalvular atrial fibrillation.

Recent findings: Registry studies have shown that the relative risk of stroke in untreated atrial fibrillation in dialysis patients is lower than in patients in the general population, but VKA are associated with increased haemorrhagic stroke in this high-risk population. A large meta-analysis of dialysis patients found no benefit of VKA in reducing stroke, but an increased bleeding risk. However, studies from Scandinavia have emphasized that risk of VKA are mitigated by increasing the time in anticoagulant therapeutic range (TTR). The consensus from the Kidney Disease: Improving Global Outcomes conference on arrhythmia in CKD was that if dialysis patients required OAC for atrial fibrillation then apixaban could be considered in preference to VKA.

Summary: Best practice prophylaxis against stroke risk in dialysis patients with atrial fibrillation is still an area of uncertainty. If OAC is indicated because of high risk, then treatment options include VKA with careful attention to increased TTR, or reduced dose apixaban, which would be off label in Europe. No RCT evidence currently exists to guide therapy, but RCTS of apixaban versus VKA in dialysis patients are currently underway.

Introduction

Patients with chronic kidney disease (CKD) are at increased risk of nonvalvular atrial fibrillation, ischaemic stroke and serious bleeding compared to people with preserved renal function. The relative risk of each of the components of this dangerous triad increases progressively with advancing CKD, being greatest in dialysis patients.[1] Historically, the mainstay of prophylactic treatment for complications of atrial fibrillation, or secondary prevention after an ischaemic stroke, has been coumarin-derived vitamin K antagonists (VKA), most notably warfarin. However, although this class of oral anticoagulants appears efficacious for these end-points in the general population and in early stage CKD, in very advanced CKD their efficacy is uncertain.[2] VKA are associated with an excess risk of serious bleeding, and their potential contribution to vascular calcification syndromes including calcific uraemic arteriolopathy has resulted in a greater awareness of the need to balance benefit and risk for optimal patient care. This awareness has intensified with the introduction of the non-vitamin K oral anticoagulants (NOAC), the factor Xa inhibitors Apixaban, Rivaroxaban and Edoxaban, and thrombin inhibitor, Dabigatran, into clinical practice. These agents appear to have at least equal efficacy to warfarin in stage 3 CKD and there is evidence that bleeding risk is comparatively lower, at least with some.[3] However, in patients with very advanced CKD and dialysis (CKD 5D) data for NOAC safety and efficacy is largely derived from observational studies and meta-analyses. In this review we set out to summarize the key studies published in this clinical area within the last 24 months, and then to synthesize current evidence to formulate a pragmatic consensus for best practice use of oral anticoagulation for nonvalvular atrial fibrillation in severe CKD – here defined as eGFR less than 30 ml/min and including patients receiving dialysis. Left atrial appendage occlusion is not associated with increased bleeding risk and early evidence of its efficacy is accumulating and this will also be discussed.

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