title: Left ventricular systolic dysfunction, heart failure, and the risk of stroke and systemic embolism in patients with atrial fibrillation: insights from the ARISTOTLE trial.
abstract: BACKGROUND
  We examined the risk of stroke or systemic embolism (SSE) conferred by heart failure (HF) and left ventricular systolic dysfunction (LVSD) in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation Trial (ARISTOTLE), as well as the effect of apixaban versus warfarin.
  
  
  RESULTS
  The risk of a number of outcomes, including the composite of SSE or death (to take account of competing risks) and composite of SSE, major bleeding, or death (net clinical benefit) were calculated in 3 patient groups: (1) no HF/no LVSD (n=8728), (2) HF/no LVSD (n=3207), and (3) LVSD with/without symptomatic HF (n=2736). The rate of both outcomes was highest in patients with LVSD (SSE or death 8.06; SSE, major bleeding, or death 10.46 per 100 patient-years), intermediate for HF but preserved LV systolic function (5.32; 7.24), and lowest in patients without HF or LVSD (1.54; 5.27); each comparison P<0.0001. Each outcome was less frequent in patients treated with apixaban: in all ARISTOTLE patients, the apixaban/warfarin hazard ratio for SSE or death was 0.89 (95% confidence interval, 0.81-0.98; P=0.02); for SSE, major bleed, or death it was 0.85 (0.78-0.92; P<0.001). There was no heterogeneity of treatment effect across the 3 groups.
  
  
  CONCLUSIONS
  Patients with LVSD (with/without HF) had a higher risk of SSE or death (but similar rate of SSE) compared with patients with HF but preserved LV systolic function; both had a greater risk than patients without either HF or LVSD. Apixaban reduced the risk of both outcomes more than warfarin in all 3 patient groups.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
authors.affiliation: BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom. john.mcmurray@glasgow.ac.uk
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ezekowitz
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Gersh
authors.forename: Sean
authors.initials: S
authors.lastname: van Diepen
authors.forename: John
authors.initials: J
authors.lastname: Amerena
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Patrick
authors.initials: P
authors.lastname: Commerford
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
authors.forename: Veli-Pekka
authors.initials: VP
authors.lastname: Harjola
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Wojdyla
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000188:drug therapy / Q000453:epidemiology*; D015897:Comorbidity; D004617:Embolism / Q000453:epidemiology* / Q000517:prevention & control; D005260:Female; D006333:Heart Failure / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D020521:Stroke / Q000453:epidemiology*; D018487:Ventricular Dysfunction, Left / Q000453:epidemiology*; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: atrial fibrillation; heart failure; left ventricular systolic dysfunction; stroke