title: Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.
abstract: BACKGROUND
  We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE.
  
  
  METHODS
  At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug.
  
  
  RESULTS
  Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial.
  
  
  CONCLUSIONS
  The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC. Electronic address: christopher.granger@duke.edu.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Lenox Hill Hospital, New York, NY.
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
authors.affiliation: Boston University Medical Center, Boston, MA.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Hylek
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Junyuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: INECO Neurociencias Oroño, Rosario, Santa Fe, Argentina.
authors.forename: M Cecilia
authors.initials: MC
authors.lastname: Bahit
authors.affiliation: Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Verheugt
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Jack
authors.initials: J
authors.lastname: Lawrence
authors.affiliation: St John's Medical College, Bangalore, India.
authors.forename: Denis
authors.initials: D
authors.lastname: Xavier
authors.affiliation: Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C522181:apixaban; D014859:Warfarin