Atrial fibrillation, a distinct form of cardiovascular disease (CVD), is common in chronic kidney disease (CKD) patients.1 It increases the risk of CKD patients developing stroke.2 Intervention with warfarin is prevalent in patients with atrial fibrillation, yet oral anticoagulant usage remains controversial in CKD patients.2 At the Advances in Medicine (AIM) conference, Prof. Cheuk-Chun Szeto from the Chinese University of Hong Kong shared his insights on the management of atrial fibrillation in CKD patients.
Atrial fibrillation is prevalent in chronic kidney disease (CKD) patients, and its prevalence increases as renal function worsens.1 For an individual with relatively mild to moderate renal dysfunction (eGFR 30-59 ml/min/1.73m2), the prevalence of atrial fibrillation is approximately 2-5%.1 If renal dysfunction is worse and the patients require chronic hemodialysis, the prevalence of atrial fibrillation reaches an average of 12-13%.1 The prevalence of atrial fibrillation is lower in peritoneal dialysis recipients, and Prof. Szeto explained that it could be due to less pressure withstood by the cardiovascular system.1
Atrial fibrillation in CKD indicates poor prognosis. It signifies 4-fold increase in the risk of stroke and 2-fold increase in mortality.2 Only half of the mortality-risk increase is stroke-associated, which suggests the risk could be due to the worsening functions of cardiovascular system.2 For stroke and bleeding risk prediction, scores such as CHA2DS2-VASc, CHADS2 and R2CHADS2, have been developed. Although these risk prediction scores are acknowledged in the general population, they can return significant yet only slightly reliable prediction in CKD patients (c-statistics: 0.61-0.68).3
Warfarin usage in CKD patients with atrial fibrillation may help minimize the risk of stroke, yet the risk of bleeding may increase.3 For patients with atrial fibrillation, having mild to moderate renal impairment, who are not required for dialysis, warfarin confers some benefits in the stroke prevention.3 However, it was shown that the risk of major bleeding is more than 2 times of the risk if CKD patients received warfarin (adjusted HR=2.24; 95% CI: 2.10-2.38; p<0.001).4 For end-stage renal disease (ESRD) patients with atrial fibrillation, most studies did not show significant benefits for taking warfarin, and the risk of major hemorrhage increases in all ESRD patients with atrial fibrillation after the use of warfarin.3 A study has even revealed that the risk of stroke rises in ESRD patients with atrial fibrillation who used warfarin, which has raised concerns that warfarin might not be safe.5 Therefore, due to the safety concerns, diet restriction and genetic polymorphism effects, warfarin may not be the best anticoagulant for CKD patients, said Prof. Szeto.6
Non-vitamin K antagonist oral anticoagulants (NOAC), such as dabigatran, apixaban, rivaroxaban and edoxaban, are available for reducing the risk of stroke. These medications offer alternatives to warfarin with different specifications in terms of antidotes, hemodialysis removal ability and renal excretion percentage.6
For patients with moderate CKD, all four NOACs show similar risk of stroke when compared to warfarin, with the exception of high-dose dabigatran (150mg), which has lowered the risk of stroke.7 On the other hand, the risk of hemorrhage is lower in patients receiving either apixaban or edoxaban.7
CKD patients of moderate-severity who are not recipients of dialysis have slightly lower risk of stroke if they consume either high dose dabigatran (150mg) or apixaban, compared to warfarin.8 Regarding the hemorrhage risk, edoxaban and apixaban were reported to be associated with reduced major bleeding events.8
Among the hemodialysis patients receiving apixaban, dabigatran, rivaroxaban or warfarin, no difference in the risk of stroke could be observed.8 However, dabigatran and rivaroxaban were associated with an increased major hemorrhage risk, while there was no major bleeding difference in apixaban compared to warfarin.8
“It’s really a balance of risk and benefit. When we encounter CKD patients with atrial fibrillation, we would need to balance the risk of hemorrhage, as well as stroke, discuss with the patients, and convey the values. Then, we will have a shared decision making together with the patients, so as to decide whether they should be put on anticoagulation, and which anticoagulant might be better for them,” said Prof. Szeto.
1. Kulkarni N, Gukathasan N, Sartori S, et al. Chronic kidney disease and atrial fibrillation: a contemporary overview. J Atr Fibrillation. 2012;5(1):448.
2. Bansal VK, Herzog CA, Sarnak MJ, et al. Oral anticoagulants to prevent stroke in nonvalvular atrial fibrillation in patients with CKD stage 5D: an NKF-KDOQI controversies report. Am J Kidney Dis. 2017;70(6):859-68.
3. Keskar V, Sood MM. Use of oral anticoagulation in the management of atrial fibrillation in patients with ESRD: con. Clin J Am Soc Nephrol. 2016;11(11):2085-92.
4. Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-35.
5. Chan KE, Lazarus JM, Thadhani R, et al. Warfarin use associates with increased risk for stroke in hemodialysis patients with atrial fibrillation. J Am Soc Nephrol. 2009;20(10):2223-33.
6. Jain N, Reilly RF. Clinical pharmacology of oral anticoagulants in patients with kidney disease. Clin J Am Soc Nephrol. 2019;14(2):278-87.
7. Shroff GR, Stoecker R, Hart A. Non-vitamin K-dependent oral anticoagulants for nonvalvular atrial fibrillation in patients with CKD: pragmatic considerations for the clinician. Am J Kidney Dis. 2018;72(5):717-27.
8. Feldberg J, Patel P, Farrell A, et al. A systematic review of direct oral anticoagulant use in chronic kidney disease and dialysis patients with atrial fibrillation. Nephrol Dial Transplant. 2019;34(2):265-77.