level 2 [mid-level] evidence

There are limited published data on the efficacy and safety of direct-acting oral anticoagulants (DOACs) in patients with end-stage renal disease (ESRD) on dialysis and atrial fibrillation. Initial DOAC trials excluded patients with ESRD. It has been suggested that when apixaban is used in patients on hemodialysis, it should be given at a reduced dose.1 A retrospective cohort study examined data from more than 25,000 Medicare beneficiaries with ESRD who were newly prescribed an anticoagulant for atrial fibrillation or atrial flutter between October 2010 and December 2015.2 Warfarin was prescribed to 23,172 patients and 2351 patients were prescribed apixaban during the 5-year time period. The authors used Medicare inpatient claims data to determine the rates of stroke, systemic embolism, major bleeding, gastrointestinal (GI) bleeding, and intracranial hemorrhage. 

The apixaban and warfarin cohorts had similar baseline characteristics after prognostic-score matching. There was no difference in the rates of ischemic stroke or symptomatic embolism, intracranial bleeding, or GI bleeding among patients prescribed apixaban compared with those prescribed warfarin. There was a statistically significant reduction in major bleeding in the apixaban group compared with the warfarin group. It is important to note that rates of major bleeding, including intracranial bleeding, were quite high in both the apixaban and warfarin groups compared with the rates reported in randomized clinical trials. Among patients prescribed apixaban, 44% were prescribed the standard dosage (5 mg twice a day), whereas 56% were prescribed a reduced dosage of 2.5 mg twice a day. In a subgroup analysis, the standard dose of apixaban was compared with warfarin and found to be associated with lower rates of stroke/systemic embolism (hazard ratio [HR] 0.64; 95% CI, 0.42-0.97), major bleeding (HR 0.71; 95% CI, 0.53-0.95), and death (HR 0.63; 95% CI, 0.46-0.85). At the reduced dose, only the major bleeding rate was lower compared with warfarin (HR 0.71; 95% CI, 0.56-0.91). At 12 months, 62.4% of patients in the apixaban group and 72.5% of patients in the warfarin group had discontinued therapy.

Related Articles

In summary, standard-dose apixaban for the treatment of atrial fibrillation in patients with ESRD may result in lower rates of major bleeding, stroke, and death compared with warfarin. Reduced-dose apixaban did not appear to be effective for reducing the rate of stroke/systemic embolism. Both the high discontinuation rate and the higher intracranial bleeding rates seen in these “real-world” data should be explored in future research.

Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Massachusetts, and assistant clinical professor in family medicine, University of Massachusetts Medical School, Worcester.

DynaMed is a database that provides evidence-based information on more than 3000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.

References

  1. Mavrakanas TA, Samer CF, Nessim SJ, Frisch G, Lipman ML. Apixaban pharmacokinetics at steady state in hemodialysis patients. J Am Soc Nephrol. 2017;28(7):2241-2248.
  2. Siontis KC, Zhang X, Eckard A, et al. Outcomes associated with apixaban use in patients with end-stage kidney disease and atrial fibrillation in the United States. Circulation. 2018;138(15):1519-1529.