Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial

Author:

Hohnloser Stefan H1,Hijazi Ziad23,Thomas Laine4,Alexander John H4,Amerena John5,Hanna Michael6,Keltai Matyas7,Lanas Fernando8,Lopes Renato D.4,Lopez-Sendon Jose9,Granger Christopher B4,Wallentin Lars2

Affiliation:

1. Division of Clinical Electrophysiology, Department of Cardiology, J.W. Goethe University, Theodor-Stern-Kai 7, Frankfurt D 60590, Germany

2. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

3. Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden

4. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA

5. Geelong Cardiology Research Center, Deakin University, Victoria, Australia

6. Bristol-Myers Squibb, Princeton, NJ, USA

7. Hungarian Institute of Cardiology, Semmelweis University, Budapest, Hungary

8. Universidad de La Frontera, Temuco, Chile

9. Hospital Universitario La Paz, Madrid, Spain

Abstract

AbstractAimsAtrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function.Methods and resultsBaseline glomerular filtration rate (GFR) was estimated using the Cockcroft–Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft–Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft–Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38–0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37–0.64), interaction P = 0.003].ConclusionIn patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

Publisher

Oxford University Press (OUP)

Subject

Cardiology and Cardiovascular Medicine

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