Atrial fibrillation (AF) and chronic kidney disease (CKD) are increasingly co-prevalent conditions as the population ages.¹ Among patients with CKD stage 5D (end-stage renal disease on dialysis), high prevalence rates of AF (>20% in some series) have been reported.^2-4 The literature is conflicted about the risk of incident stroke among CKD 5D patients with AF. Some registries suggest a higher hazard of stroke/thromboembolic disease among CKD 5D patients with AF;⁵ however, other cohorts of CKD 5D patients have failed to demonstrate an increase in incident stroke among patients with AF.^3,6 Yet, it appears quite clear that AF increases the mortality hazard in this high-risk population.³ Multiple new oral anticoagulant (NOAC) agents have been studied for thromboembolic prophylaxis in the setting of non-valvular AF in the general population. Although convenient from a patient perspective due to lack of need for monitoring and less dietary interactions than warfarin, the lack of a readily available reversal agent remains a concern. Most of the NOACs have high renal clearance, but none have been specifically studied in the context of CKD 5D.

Thromboembolic prophylaxis in CKD 5D with AF is complex and controversial. Although several investigations attempted to evaluate appropriate ways to reduce the risk of stroke in this high-risk population, the substantial risk of bleeding tends to negate the net beneficial effects of anticoagulation in several studies. Although difficult to accurately glean from observational data alone, there is some suggestion for benefit of warfarin in stroke prevention among CKD 5D patients⁵ but a significantly higher concern about bleeding risk.^7-9 Moreover, some observational data have demonstrated a higher hazard of stroke among CKD 5D patients with AF on warfarin.¹⁰ Due to the ambiguity in the literature, the latest Kidney Disease: Improving Global Outcomes (KDIGO) opinion states that the evidence is not compelling to recommend routine anticoagulation of CKD 5D patients with AF for primary prevention of stroke.¹¹ Current 2014 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines report that it is reasonable to consider warfarin therapy for CKD 5D patients with non-valvular AF and moderate conventional risk factors (Class of Recommendation IIA, Level of Evidence B). There are limited data regarding the use of NOACs in CKD 5D patients, as they were excluded from RCTs. However, apixaban has received U.S. Food and Drug Administration (FDA) approval for prevention of stroke/systemic embolism in the setting of AF among CKD 5D patients.¹² The usual dose of apixaban 5 mg PO twice daily is recommended to be reduced to 2.5 mg twice daily for these patients if age >80 years or weight <60 kg. Because of significant ambiguity in the literature about best practices in treating patients with CKD 5D, the authors of this article believe that a randomized trial is necessary to inform management, and, in this regard, certainly agree that a "pint of sweat may save a gallon of blood."¹³

References

1. Shroff GR, Solid CA, Herzog CA. Atrial fibrillation, stroke, and anticoagulation in medicare beneficiaries: trends by age, sex, and race, 1992-2010. J Am Heart Assoc 2014;3:e000756.
2. Wetmore JB, Mahnken JD, Rigler SK, et al. The prevalence of and factors associated with chronic atrial fibrillation in Medicare/Medicaid-eligible dialysis patients. Kidney Int 2012;81:469-76.
3. Genovesi S, Vincenti A, Rossi E, et al. Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients. Am J Kidney Dis 2008;51:255-62.
4. Tumlin JA, Charytan DM, Williamson DE, et al. Frequency and distribution of dialysis-associated atrial fibrillation: results of MiD study. J Am Soc Nephrol 2014;25:35A.
5. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012;367:625-35.
6. Shah M, Avgil TM, Jackevicius CA, et al. Warfarin use and the risk for stroke and bleeding in patients with atrial fibrillation undergoing dialysis. Circulation 2014;129:1196-203.
7. Elliott MJ, Zimmerman D, Holden RM. Warfarin anticoagulation in hemodialysis patients: a systematic review of bleeding rates. Am J Kidney Dis 2007;50:433-40.
8. Holden RM, Harman GJ, Wang M, Holland D, Day AG. Major bleeding in hemodialysis patients. Clin J Am Soc Nephrol 2008;3:105-10.
9. Wizemann V, Tong L, Satayathum S, et al. Atrial fibrillation in hemodialysis patients: clinical features and associations with anticoagulant therapy. Kidney Int 2010;77:1098-106.
10. Chan KE, Lazarus JM, Thadhani R, Hakim RM. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol 2009;20:2223-33.
11. Herzog CA, Asinger RW, Berger AK, et al. Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011;80:572-86.
12. U.S. Department of Health & Human Services. Eliquis (apixaban) 2.5 and 5 mg. Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) (FDA website). 2014. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm384790.htm. Accessed 3/4/15.
13. Granger CB, Chertow GM. A pint of sweat will save a gallon of blood: a call for randomized trials of anticoagulation in end-stage renal disease. Circulation 2014; 129:1190-2.

Keywords: American Heart Association, Anticoagulants, Atrial Fibrillation, Cytarabine, Embolism, Kidney Failure, Chronic, Prevalence, Primary Prevention, Pyrazoles, Pyridones, Registries, Renal Dialysis, Renal Insufficiency, Chronic, Risk Factors, Stroke, Sulfonamides, Sweat, Thromboembolism, Triazines, Warfarin, Geriatrics

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