Warfarin therapy for atrial fibrillation in haemodialysis patients: mind the (evidence) gap

Atrial Fibrillation (AFib) is the most frequent sustained arrhythmia in patients with kidney disease. Although the indications for anticoagulant therapy for AFib patients have become much refined during the last decade, there is clinical equipoise regarding the safety versus the effectiveness of warfarin in AFib patients undergoing chronic haemodialysis. Due to the complex nature of advanced kidney disease, which predisposes to both ischaemic stroke and bleeding [1], this condition poses concerns regarding warfarin effectiveness in stroke prevention as well as its safety as it may exacerbate the already high bleeding risk [2]. This equipoise is clearly reflected in the discordant recommendations from current guidelines: while the current American Heart Association/American College of Cardiology (AHA/ACC/HRS) guidelines [3] generally recommend the use of warfarin for primary stroke prevention in haemodialysis patients, the Kidney Disease Improving Global Outcomes (KDIGO) [4] advises against it because of the unknown net clinical benefit. Several observational reports of AFib patients undergoing haemodialysis have associated warfarin use with an increased risk of bleeding, higher stroke risk or lack of stroke risk prevention [5–8]. These associations may not be entirely universal, but perhaps confined to special high-risk subpopulations, such as individuals above 75 years of age [7], or receiving high warfarin dosages [5] presumably denoting poor international normalized ratio (INR) control. A recent small report even observed a slightly faster aortic stiffness progression among warfarin users undergoing haemodialysis when compared with matched non-users [9]. Opposing these worrying reports, nevertheless, an equal number of studies favour warfarin use in this patient population, describing a significant association to both reduced mortality and stroke risk, without increased risk of bleeding [10–12]. Because the community-proven net clinical benefit of warfarin [13] seems preserved in individuals with moderate/advanced kidney disease [8, 10, 12, 14] or in kidney transplant recipients [15], we may conclude that the equipoise pertains to dialysis patients only. The haemodialysis procedure may indeed be a trigger for AFib, as monitoring with implantable cardioverter defibrillators showed that AFib occurred significantly more often on a dialysis day and especially during the haemodialysis session, persisting a few hours thereafter [16]. The absence of studies addressing this problem in peritoneal dialysis patients creates an important knowledge gap for this considerable renal replacement therapy segment.