Abstract | BACKGROUND: METHODS: 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. 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.
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Authors | John W Stanifer, Sean D Pokorney, Glenn M Chertow, Stefan H Hohnloser, Daniel M Wojdyla, Samira Garonzik, Wonkyung Byon, Ziad Hijazi, Renato D Lopes, John H Alexander, Lars Wallentin, Christopher B Granger |
Journal | Circulation
(Circulation)
Vol. 141
Issue 17
Pg. 1384-1392
(04 28 2020)
ISSN: 1524-4539 [Electronic] United States |
PMID | 32160801
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anticoagulants
- Pyrazoles
- Pyridones
- apixaban
- Warfarin
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Topics |
- Aged
- Aged, 80 and over
- Anticoagulants
(administration & dosage, adverse effects, pharmacokinetics)
- Atrial Fibrillation
(blood, drug therapy, epidemiology)
- Double-Blind Method
- Female
- Hemorrhage
(blood, chemically induced, epidemiology)
- Humans
- Male
- Proportional Hazards Models
- Pyrazoles
(administration & dosage, adverse effects, pharmacokinetics)
- Pyridones
(administration & dosage, adverse effects, pharmacokinetics)
- Renal Insufficiency, Chronic
(blood, drug therapy, epidemiology)
- Warfarin
(administration & dosage, adverse effects, pharmacokinetics)
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