title: Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial.
abstract: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban therapy was superior to warfarin therapy in preventing stroke and all-cause death while causing significantly fewer major bleeds. To establish the value proposition of substituting apixiban therapy for warfarin therapy in patients with atrial fibrillation, we performed a cost-effectiveness analysis using patient-level data from the ARISTOTLE trial.
  
  
  
  To assess the cost and cost-effectiveness of apixaban therapy compared with warfarin therapy in patients with atrial fibrillation from the perspective of the US health care system.
  
  
  
  This economic analysis uses patient-level resource use and clinical data collected in the ARISTOTLE trial, a multinational randomized clinical trial that observed 18 201 patients (3417 US patients) for a median of 1.8 years between 2006 and 2011.
  
  
  
  Apixaban therapy vs warfarin therapy.
  
  
  
  Within-trial resource use and cost were compared between treatments, using externally derived US cost weights. Life expectancies for US patients were estimated according to their baseline risk and treatment using time-based and age-based survival models developed using the overall ARISTOTLE population. Quality-of-life adjustment factors were obtained from external sources. Cost-effectiveness (incremental cost per quality-adjusted life-year gained) was evaluated from a US perspective, and extensive sensitivity analyses were performed.
  
  
  
  Of the 3417 US patients enrolled in ARISTOTLE, the mean (SD) age was 71 (10) years; 2329 (68.2%) were male and 3264 (95.5%) were white. After 2 years of anticoagulation therapy, health care costs (excluding the study drug) of patients treated with apixaban therapy and warfarin therapy were not statistically different (difference, -$60; 95% CI, -$2728 to $2608). Life expectancy, modeled from ARISTOTLE outcomes, was significantly longer with apixaban therapy vs warfarin therapy (7.94 vs 7.54 quality-adjusted life years). The incremental cost, including cost of anticoagulant and monitoring, of achieving these benefits was within accepted US norms ($53 925 per quality-adjusted life year, with 98% likelihood of meeting a $100 000 willingness-to-pay threshold). Results were generally consistent when model assumptions were varied, with lifetime cost-effectiveness most affected by the price of apixaban and the time horizon.
  
  
  
  Apixaban therapy for ARISTOTLE-eligible patients with atrial fibrillation provides clinical benefits at an incremental cost that represents reasonable value for money judged using US benchmarks for cost-effectiveness.
  
  
  
  clinicaltrials.gov Identifier: NCT00412984.
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cowper
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Shubin
authors.initials: S
authors.lastname: Sheng
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Anstrom
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Stafford
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Linda
authors.initials: L
authors.lastname: Davidson-Ray
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Sana M
authors.initials: SM
authors.lastname: Al-Khatib
authors.affiliation: Department of Medicine, Hofstra Northwell School of Medicine, Hemstead, New York.
authors.forename: Jack
authors.initials: J
authors.lastname: Ansell
authors.affiliation: Division of Cardiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Dorian
authors.affiliation: Aarhus University, Aarhus, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland.
authors.forename: John J V
authors.initials: JJV
authors.lastname: McMurray
authors.affiliation: Université Paris-Diderot, Sorbonne Paris Cité, French Alliance for Cardiovascular Clinical Trials, Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling, Assistance-Publique-Hôpitaux de Paris and Institut National de la Santé et de la Recherche Médicale U-1148, Paris, France7National Heart and Lung Institute, Royal Brompton Hospital, Imperial College, London, England.
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
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, North Carolina.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Mark
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000191:economics / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000191:economics; D002423:Cause of Death; D003362:Cost-Benefit Analysis; D065427:Factor Xa Inhibitors / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D017048:Health Care Costs; D006470:Hemorrhage / Q000139:chemically induced / Q000191:economics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000191:economics / Q000627:therapeutic use*; D011728:Pyridones / Q000191:economics / Q000627:therapeutic use*; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D020521:Stroke / Q000191:economics / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D015996:Survival Rate; D014481:United States; D014859:Warfarin / Q000191:economics / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin