title: Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial.
abstract: We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD.
  
  
  
  The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P=0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03).
  
  
  
  Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD.
  
  
  
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Hu
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.|Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Laine
authors.initials: L
authors.lastname: Thomas
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.|Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.affiliation: Bristol-Myers Squibb, Princeton, NJ.
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.affiliation: Lady Davis Carmel Medical Center, The Ruth and Bruce Rappaport School of Medicine of the Technion, Haifa, Israel.
authors.forename: Basil S
authors.initials: BS
authors.lastname: Lewis
authors.affiliation: Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC.|Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC schuyler.jones@dm.duke.edu.|Duke Clinical Research Institute, Duke University Medical Center, Durham, NC.
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D016022:Case-Control Studies; D004311:Double-Blind Method; D004617:Embolism / Q000209:etiology / Q000517:prevention & control*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000150:complications*; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin
keywords: apixaban; atrial fibrillation; bleeding; peripheral artery disease; stroke; systemic embolism