Safety and effectiveness of apixaban versus warfarin by kidney function in atrial fibrillation: a binational population-based study

Background — Evidence to guide use of apixaban in people with atrial fibrillation (AF) and chronic kidney disease (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 5 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 <30mL/min/1.73m2 were included. Patients on dialysis or kidney transplant recipients were excluded. We assessed outcomes within one 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 [CIs]) 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 one year. Apixaban was associated with lower or similar risk for the ischemic outcome compared with warfarin in all eGFR categories (pooled HRs [95% CI]: 0.78 [0.64-0.94]), 0.77 [0.62-0.97], 0.82 [0.68-0.98] and 0.99 [0.68-1.45] for eGFR >60, 45-59, 30-44 and <30mL/min/1.73m2 respectively). Apixaban was associated with lower or similar risk of bleeding across the range of kidney function (pooled HRs: 0.55 [0.43-0.69], 0.73 [0.52-1.02], 0.55 [0.31-0.97], 0.68 [0.47-0.99], 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 apixaban offers a favorable risk-benefit ratio in patients with AF independent of kidney function.