Standard dose of apixaban for patients with ESRD and atrial fibrillation appears better than warfarin or reduced dose apixaban
EBM Focus - Volume 13, Issue 38
Reference: Circulation. 2018 Oct 9;138(15):1519 (level 2 [mid-level] evidence)
There is limited published data on the efficacy and safety of direct acting anticoagulants (DOACs) in patients with end-stage renal disease (ESRD) on dialysis with atrial fibrillation. Initial DOAC trials excluded patients with ESRD. It has been suggested that when apixiaban is used in patients on hemodialysis, it should be given at a reduced dose (J Am Soc Nephrol. 2017). A retrospective cohort study examined data from over 25,000 Medicare beneficiaries with ESRD who were newly prescribed an anticoagulant for atrial fibrillation or atrial flutter (AF) between October 2010 and December 2015 (Circulation. 2018 Oct 9). Warfarin was prescribed to 23,172 patients and 2,351 patients were prescribed apixaban during the five year time period. The authors used Medicare inpatient claims data to determine the rates of stroke, systemic embolism, major bleeding, 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 to those prescribed warfarin. There was a statistically significant reduction in major bleeding in the apixaban group compared to 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 to the rates reported in randomized clinical trials. Among patients prescribed apixaban, 44% were prescribed standard dose (5 mg BID), whereas 56% were prescribed 2.5 mg BID. In a subgroup analysis, the standard dose of apixaban was compared to warfarin and found to be associated with lower rate 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 major bleeding rates were lower compared to 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 the warfarin group had discontinued therapy. Both the high discontinuation rate and the higher intracranial bleeding rates seen in this ‘real world’ data should be explored in future research.
Focus Point: Standard dose apixaban for the treatment of atrial fibrillation in ESRD patients may result in lower rates of major bleeding, stroke, and death as compared to warfarin. Reduced dose apixaban did not appear to be effective for reducing the rate of stroke/systemic embolism.
DynaMed Plus EBM Focus Editorial Team
This EBM Focus was written by Carina Brown, MD, Faculty Development and Information Mastery Fellow and Clinical Instructor at the University of Virginia. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed Plus and Associate Professor in Family Medicine at the University of Massachusetts Medical School and Katharine DeGeorge, MD, MS, Assistant Professor in Family Medicine at the University of Virginia and Clinical Editor at DynaMed Plus.