title: Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial.
abstract: OBJECTIVE
  Atrial 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.
  
  
  RESULTS
  Baseline 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].
  
  
  CONCLUSIONS
  In 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.
authors.affiliation: Division of Clinical Electrophysiology, Department of Cardiology, J. W. Goethe University, Theodor-Stern-Kai 7, Frankfurt D 60590, Germany. hohnloser@em.uni-frankfurt.de
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Hohnloser
authors.forename: Ziad
authors.initials: Z
authors.lastname: Hijazi
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: John
authors.initials: J
authors.lastname: Amerena
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Matyas
authors.initials: M
authors.lastname: Keltai
authors.forename: Fernando
authors.initials: F
authors.lastname: Lanas
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Sendon
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin