title: Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial.
abstract: OBJECTIVE
  We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF).
  
  
  RESULTS
  In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease.
  
  
  CONCLUSIONS
  Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.
authors.affiliation: Duke Clinical Research Institute, Duke Medicine, Duke University Medical Center, Box 3850, Durham, NC 27710, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.forename: Marco
authors.initials: M
authors.lastname: Alings
authors.forename: Dan
authors.initials: D
authors.lastname: Atar
authors.forename: Philip
authors.initials: P
authors.lastname: Aylward
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.forename: John J V
authors.initials: JJ
authors.lastname: McMurray
authors.forename: Prem
authors.initials: P
authors.lastname: Pais
authors.forename: Hubert
authors.initials: H
authors.lastname: Pouleur
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Wojdyla
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004617:Embolism / Q000517:prevention & control; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D020521:Stroke / 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; D001241:Aspirin
keywords: Aspirin; Atrial fibrillation; Concomitant medications; Major bleeding; Stroke; Systemic embolism