Safety and Effectiveness of Apixaban versus Warfarin by Kidney Function in Atrial Fibrillation: A Binational Population-Based Study

Abstract

Key Points:

1. This real-world study involved a large cohort of 38,598 adults with atrial fibrillation from five jurisdictions across Australia and Canada.

2. This study supports the use of apixaban as a safe and effective alternative to warfarin for atrial fibrillation across differing levels of kidney function.

3. This study also adds important safety data on the use of apixaban in patients with reduced kidney function.

Background: Evidence to guide the use of apixaban in people with atrial fibrillation (AF) and CKD in routine clinical practice has been limited. We assessed comparative safety (major bleeding) and effectiveness (ischemic stroke and death) of apixaban versus warfarin in patients with AF across the spectrum of non–dialysis-dependent CKD using large, routinely collected data.

Methods: We combined findings from five retrospective cohorts (2013–2018) across Australia and Canada. Adults with AF, new dispensation of apixaban or warfarin, and a recorded eGFR grouped as ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m² were included. Patients on dialysis or kidney transplant recipients were excluded. We assessed outcomes within 1 year of initiating either therapy: (1) composite of all-cause death, ischemic stroke, or transient ischemic attack and (2) first hospitalization for major bleeding (intracranial, gastrointestinal, or other). Cox models estimated hazard ratios (HRs; 95% confidence intervals) for outcomes across eGFR categories, after 1:1 matching using propensity scores. We summarized center-level data using random effects meta-analysis.

Results: Among 38,598 matched apixaban and warfarin users, there were 4130 (10.7%) ischemic and 697 (1.8%) bleeding events within 1 year. Apixaban was associated with lower or similar risk for the ischemic outcome compared with warfarin in all eGFR categories (pooled HRs [95% confidence interval]: 0.78 [0.64 to 0.94], 0.77 [0.62 to 0.97], 0.82 [0.68 to 0.98], and 0.99 [0.68 to 1.45] for eGFR ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m², respectively). Apixaban was associated with lower or similar risk of bleeding across the range of kidney function (pooled HRs: 0.55 [0.43 to 0.69], 0.73 [0.52 to 1.02], 0.55 [0.31 to 0.97], and 0.68 [0.47 to 0.99], respectively). There was no significant heterogeneity across jurisdictions or eGFR categories.

Conclusions: In adults with AF and non–dialysis-dependent CKD, apixaban compared with warfarin was associated with lower or similar risk of ischemic and bleeding outcomes. Our results suggest that apixaban offers a favorable risk-benefit ratio in patients with AF independent of kidney function.

Keywords: CKD; GFR; cardiovascular disease; epidemiology and outcomes.

Graphical abstract

Figure 1

Identification of study cohort. DOAC, direct oral anticoagulant.

Figure 2

Hazard ratios (95% CIs) for the effectiveness outcome by eGFR category. CI, confidence interval; EXTEND45, EXamining ouTcomEs in chroNic Disease in the 45 and Up; PROMIS, Patient Records and Outcome Management Information System; S, number of outcome events <5 and cells were suppressed to meet privacy restrictions.

Figure 3

Hazard ratios (95% CIs) for the major bleeding outcome by eGFR category.

Figure 4

Sensitivity analyses. (A) Sensitivity analyses assessing the comparative effectiveness of apixaban and warfarin according to eGFR category. (B) Sensitivity analyses assessing the comparative safety (major bleeding) of apixaban and warfarin according to eGFR category.

Figure 4

Sensitivity analyses. (A) Sensitivity analyses assessing the comparative effectiveness of apixaban and warfarin according to eGFR category. (B) Sensitivity analyses assessing the comparative safety (major bleeding) of apixaban and warfarin according to eGFR category.