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Apixaban versus Warfarin in Patients with Atrial Fibrillation and Advanced Chronic Kidney Disease. Circulation Stanifer, J. W., Pokorney, S. D., Chertow, G. M., Hohnloser, S. H., Wojdyla, D. M., Garonzik, S. n., Byon, W. n., Hijazi, Z. n., Lopes, R. D., Alexander, J. H., Wallentin, L. n., Granger, C. B. 2020

Abstract

Background: Compared with the general population, patients with advanced chronic kidney disease (CKD) have a >10-fold higher burden of atrial fibrillation (AF). Limited data are available guiding the use of non-vitamin K antagonist oral anticoagulants in this population. Methods: We compared the safety of apixaban with warfarin in 269 patients with AF and advanced CKD (defined as creatinine clearance [CrCl] 25-30 mL/min) enrolled in ARISTOTLE. Cox proportional models were used to estimate hazard ratios (HRs) for major bleeding and major or clinically relevant non-major (CRNM) bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using non-linear mixed effects models. Results: Among patients with CrCl 25-30 mL/min, apixaban caused less major bleeding (HR 0.34, 95% confidence interval [CI] 0.14-0.80) and major or CRNM bleeding (HR 0.35, 95% CI 0.17-0.72) compared with warfarin. Patients with CrCl 25-30 mL/min randomized to apixaban demonstrated a trend towards lower rates of major bleeding when compared with those with CrCl >30 mL/min (p interaction=0.08) and major or CRNM bleeding (p interaction=0.05). Median daily steady state areas under the curve (AUCss) for apixaban 5 mg twice daily were 5512 ng/mL*hr and 3406 ng/mL*hr for patients with CrCl 25-30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/mL*hr for patients with CrCl 25-30 mL/min. The AUC values for patients with CrCl 25-30 mL/min fell completely within the ranges demonstrated for patients with CrCl >30 mL/min. Conclusions: Among patients with AF and CrCl 25-30 mL/min, apixaban caused less bleeding than warfarin, with even greater reductions in bleeding than in patients with CrCl >30 mL/min. We observed substantial overlap in the range of exposure to apixaban 5 mg twice daily for patients with or without advanced CKD, supporting conventional dosing in patients with CrCl 25-30 mL/min. Randomized controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced CKD, including those receiving dialysis. Clinical Trial Registration: URL: https://ClinicalTrials.gov Unique Identifier: NCT00412984.

View details for DOI 10.1161/CIRCULATIONAHA.119.044059

View details for PubMedID 32160801