In a recent review of treatment options for patients with atrial fibrillation who also have advanced chronic kidney disease (CKD), researchers compared the benefits and risks of nonvitamin-K oral anticoagulants (NOACS) to warfarin.
“The 2014 AHA, ACC, and HRS [American Heart Association, American College of Cardiology, and Heart Rhythm Society] guideline for the management of patients with AF [atrial fibrillation] states that it is reasonable to prescribe warfarin (international normalized ratio 2.0 to 3.0) to patients with nonvalvular AF with CHA2DS2-VASC scores of 2 or greater who have CrCl [creatinine clearance] <15 ml/min or are on hemodialysis,” the authors wrote. “In contrast, the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines state that routine anticoagulation of dialysis patients with AF for the primary prevention of stroke is not indicated.”
Researchers stressed that the degree to which warfarin and NOACS reduce the risk of stroke in patients with advanced CKD or end-stage renal disease (ESRD) remains unclear. In the general population, studies have suggested that warfarin may reduce the risk of stroke by 64% in patients with atrial fibrillation vs placebo. However, there is also some evidence that anticoagulation does not produce the same outcomes in patients with advanced CKD and ESRD.
“If oral anticoagulation is indicated and the perceived benefits outweigh the risks for therapy, the 2014 AHA, ACC, and HRS guidelines endorse warfarin as the first-line therapy in patients with CKD stage 4 (creatinine clearance 15 to 30 ml/min) or CKD state 5 (creatinine clearance <15 ml/min) or on dialysis, because all NOACS partially rely on the kidney for elimination,” they wrote.
While the US label for NOACS indicates they may be used even when a patient’s creatinine clearance is as low as 15 ml/min, this practice should be implemented with “extreme caution,” as these recommendations were mostly based on pharmacokinetic data and limited efficacy data support it. Those studies are only “moderately reliable” for quantifying NOAC dose with drug exposure and anticoagulation level (eg, factor Xa activity).
Furthermore, in the rare instance when patients with advanced CKD are prescribed NOACS, renal function must be closely monitored—as often as every 2 to 4 months and during acute illness. The suggested dose is apixaban 2.5 to 5 mg twice daily for patients on dialysis. Alternatively, rivaroxaban or edoxaban at lower doses may also be effective. Dabigatran is considered a less-than-ideal choice because of its risk to increase bleeding when creatinine clearance drops below 50 ml/min. Drug levels may substantially fluctuate with dialysis treatment, particularly because dialysis clears 50% to 60% of the drug.
Nonetheless, the researchers concluded, “NOAC use in patients with advanced CKD and on dialysis is substantial and increasing, despite AHA, ACC, and HRS and European Heart Rhythm Association guidelines that endorse warfarin as the anticoagulant of choice when CrCl is <30 ml/min.”
Ultimately, randomized controlled clinical trials are necessary to confirm the clinical efficacy and safety of NOACS compared with placebo in patients who have atrial fibrillation with advanced CKD and on dialysis.
Chan KE, Giugliano RP, Patel MR, et al. Nonvitamin K anticoagulant agents in patients with advanced chronic kidney disease or on dialysis with AF. J Am Coll Cardiol. 2016;67(24):2888-2899. doi: 10.1016/j.jacc.2016.02.082.