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Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.
- Source :
-
Circulation [Circulation] 2020 Apr 28; Vol. 141 (17), pp. 1384-1392. Date of Electronic Publication: 2020 Mar 12. - Publication Year :
- 2020
-
Abstract
- Background: Compared with the general population, patients with advanced chronic kidney disease have a >10-fold higher burden of atrial fibrillation. Limited data are available guiding the use of nonvitamin K antagonist oral anticoagulants in this population.<br />Methods: We compared the safety of apixaban with warfarin in 269 patients with atrial fibrillation and advanced chronic kidney disease (defined as creatinine clearance [CrCl] 25 to 30 mL/min) enrolled in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation). Cox proportional models were used to estimate hazard ratios for major bleeding and major or clinically relevant nonmajor bleeding. We characterized the pharmacokinetic profile of apixaban by assessing differences in exposure using nonlinear mixed effects models.<br />Results: Among patients with CrCl 25 to 30 mL/min, apixaban caused less major bleeding (hazard ratio, 0.34 [95% CI, 0.14-0.80]) and major or clinically relevant nonmajor bleeding (hazard ratio, 0.35 [95% CI, 0.17-0.72]) compared with warfarin. Patients with CrCl 25 to 30 mL/min randomized to apixaban demonstrated a trend toward lower rates of major bleeding when compared with those with CrCl >30 mL/min ( P interaction=0.08) and major or clinically relevant nonmajor bleeding ( P interaction=0.05). Median daily steady-state areas under the curve for apixaban 5 mg twice daily were 5512 ng/(mL·h) and 3406 ng/(mL·h) for patients with CrCl 25 to 30 mL/min or >30 mL/min, respectively. For apixaban 2.5 mg twice daily, the median exposure was 2780 ng/(mL·h) for patients with CrCl 25 to 30 mL/min. The area under the curve values for patients with CrCl 25 to 30 mL/min fell within the ranges demonstrated for patients with CrCl >30 mL/min.<br />Conclusions: Among patients with atrial fibrillation and CrCl 25 to 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 chronic kidney disease, supporting conventional dosing in patients with CrCl 25 to 30 mL/min. Randomized, controlled studies evaluating the safety and efficacy of apixaban are urgently needed in patients with advanced chronic kidney disease, including those receiving dialysis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.
- Subjects :
- Aged
Aged, 80 and over
Double-Blind Method
Female
Hemorrhage blood
Hemorrhage chemically induced
Hemorrhage epidemiology
Humans
Male
Proportional Hazards Models
Renal Insufficiency, Chronic blood
Renal Insufficiency, Chronic drug therapy
Renal Insufficiency, Chronic epidemiology
Anticoagulants administration & dosage
Anticoagulants adverse effects
Anticoagulants pharmacokinetics
Atrial Fibrillation blood
Atrial Fibrillation drug therapy
Atrial Fibrillation epidemiology
Pyrazoles administration & dosage
Pyrazoles adverse effects
Pyrazoles pharmacokinetics
Pyridones administration & dosage
Pyridones adverse effects
Pyridones pharmacokinetics
Warfarin administration & dosage
Warfarin adverse effects
Warfarin pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 141
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 32160801
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.119.044059