title: Efficacy and safety of apixaban compared with warfarin at different levels of predicted international normalized ratio control for stroke prevention in atrial fibrillation.
abstract: BACKGROUND
  In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced stroke and systemic embolism, major bleeding, and mortality. We evaluated treatment effects in relation to 2 predictions of time in therapeutic range (TTR).
  
  
  RESULTS
  The trial randomized 18 201 patients with atrial fibrillation to apixaban 5 mg twice daily or warfarin for at least 12 months. For each patient, a center average TTR was estimated with the use of a linear mixed model on the basis of the real TTRs in its warfarin-treated patients, with a fixed effect for country and random effect for center. For each patient, an individual TTR was also predicted with the use of a linear mixed effects model including patient characteristics as well. Median center average TTR was 66% (interquartile limits, 61% and 71%). Rates of stroke or systemic embolism, major bleeding, and mortality were consistently lower with apixaban than with warfarin across center average TTR and individual TTR quartiles. In the lowest and highest center average TTR quartiles, hazard ratios for stroke or systemic embolism were 0.73 (95% confidence interval [CI], 0.53-1.00) and 0.88 (95% CI, 0.57-1.35) (Pinteraction=0.078), for mortality were 0.91 (95% CI, 0.74-1.13) and 0.91 (95% CI, 0.71-1.16) (Pinteraction=0.34), and for major bleeding were 0.50 (95% CI, 0.36-0.70) and 0.75 (95% CI, 0.58-0.97) (Pinteraction=0.095), respectively. Similar results were seen for quartiles of individual TTR.
  
  
  CONCLUSIONS
  The benefits of apixaban compared with warfarin for stroke or systemic embolism, bleeding, and mortality appear similar across the range of centers' and patients' predicted quality of international normalized ratio control.
authors: Uppsala Clinical Research Center, Uppsala University, Dag Hammarskjölds väg 14B, Uppsala, Sweden. Lars.Wallentin@ucr.uu.se
authors: Lars
authors: L
authors: Wallentin
authors: Renato D
authors: RD
authors: Lopes
authors: Michael
authors: M
authors: Hanna
authors: Laine
authors: L
authors: Thomas
authors: Anne
authors: A
authors: Hellkamp
authors: Sunil
authors: S
authors: Nepal
authors: Elaine M
authors: EM
authors: Hylek
authors: Sana M
authors: SM
authors: Al-Khatib
authors: John H
authors: JH
authors: Alexander
authors: Marco
authors: M
authors: Alings
authors: John
authors: J
authors: Amerena
authors: Jack
authors: J
authors: Ansell
authors: Philip
authors: P
authors: Aylward
authors: Jozef
authors: J
authors: Bartunek
authors: Patrick
authors: P
authors: Commerford
authors: Raffaele
authors: R
authors: De Caterina
authors: Cetin
authors: C
authors: Erol
authors: Veli-Pekka
authors: VP
authors: Harjola
authors: Claes
authors: C
authors: Held
authors: John D
authors: JD
authors: Horowitz
authors: Kurt
authors: K
authors: Huber
authors: Steen
authors: S
authors: Husted
authors: Matyas
authors: M
authors: Keltai
authors: Fernando
authors: F
authors: Lanas
authors: Liu
authors: L
authors: Lisheng
authors: John J V
authors: JJ
authors: McMurray
authors: Byung-Hee
authors: BH
authors: Oh
authors: Mårten
authors: M
authors: Rosenqvist
authors: Witold
authors: W
authors: Ruzyllo
authors: Philippe Gabriel
authors: PG
authors: Steg
authors: Dragos
authors: D
authors: Vinereanu
authors: Denis
authors: D
authors: Xavier
authors: Christopher B
authors: CB
authors: Granger
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: anticoagulation; apixaban; atrial fibrillation; bleeding; stroke; warfarin