Patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) are at greater risk for stroke. However, it remains controversial whether anticoagulation is of benefit in these patients due to the high bleeding risk. In Revista Española de Cardiología, Mahmood and Lip published an article on anticoagulation therapy in AF patients with ESRD.1 Some points should be further discussed.
The CHA2DS2-VASC score is broadly used for predicting the risk of ischemic stroke in patients with AF. However, it has not been validated in patients with ESRD and AF. Other proposed risk score algorithms that include chronic kidney disease in the model, such as the R2CHADS2 score, have shown no added value.2 Recently, Chao et al.3 reported that the CHA2DS2-VASC score was useful in predicting ischemic stroke in AF patients with ESRD. However, the authors suggested that anticoagulant therapy may be suitable for these patients when CHA2DS2-VASC score ≥ 6, due to the greater risk of bleeding. Based on these studies, there is a need to develop a specific scoring system for anticoagulation in AF patients with ESRD. If the CHA2DS2-VASC score is used, the cutpoint for recommendation of anticoagulation in ESRD should be further evaluated.
The article by Mahmood and Lip states that there is more evidence supporting warfarin for its use in AF patients with ESRD. However, observational studies have shown that the use of warfarin was not associated with a reduction in stroke risk or mortality in AF patients with ESRD, but with greater bleeding risk.4 The lack of data on quality of warfarin anticoagulation (eg, time in therapeutic range) may be a potential confounder in such observational studies. However, in real-world clinical practice, the target of time in therapeutic range is hard to achieve in patients with ESRD. Currently, given the lack of clear evidence, the European Heart Rhythm Association does not provide any recommendations,5 whereas the Kidney Disease: Improving Global Outcomes (KDIGO) consensus6 caution against the routine use of any oral anticoagulation therapy in AF patients with ESRD. Given the lack of randomized control trials, anticoagulation therapy (using warfarin or any nonvitamin K antagonist oral anticoagulants) for AF patients with ESRD is still a matter of debate.
Nowadays, apixaban is approved for use in AF patients with ESRD by the Food and Drug Administration, but not in other contexts. A retrospective cohort study showed that there was no difference in the risks of stroke between apixaban and warfarin, but apixaban was associated with a lower risk of major bleeding.7 As mentioned in the article by Mahmood and Lip, 2 ongoing randomized control trials,4 the RENAL-AF and AXADIA study, are evaluating the safety and efficacy of apixaban vs warfarin or phenprocoumon, respectively. However, none of these trials included a control group with no oral anticoagulation, which is needed to access whether anticoagulation therapy is of benefit in these patients. It is important to wait for the results of the Oral Anticoagulation in Haemodialysis Patients (AVKDIAL) study, which will compare the hemorrhagic and thrombotic risks of vitamin K antagonists with no anticoagulation in hemodialysis patients with AF.
In conclusion, considering the strong uncertainty and conflicting results about anticoagulation in AF patients with ESRD, we advocate the following: a) the development of specific scoring systems for the prediction of stroke and bleeding; and b) the need for randomized control trials evaluating the risk-to-benefit ratio of anticoagulation compared with placebo instead of comparing various oral anticoagulants in this population.
CONFLICTS OF INTERESTY. Huang received research funding from the National Natural Science Foundation of China (No: 81600239) and Scientific Research Fund of Foshan, China (No: 2016AB003353). All the other authors declare they have no conflicts of interest.