title: Cost-effectiveness of edoxaban vs warfarin in patients with atrial fibrillation based on results of the ENGAGE AF-TIMI 48 trial.
abstract: BACKGROUND
  In 21,105 patients with atrial fibrillation (AF), the ENGAGE AF-TIMI 48 trial demonstrated that both higher dose (60mg/30mg dose reduced) and lower dose (30mg/15mg dose reduced) once-daily regimens of edoxaban were non-inferior to warfarin for the prevention of stroke or systemic embolism (SE), with significantly lower rates of bleeding and cardiovascular death. Higher dose edoxaban was associated with a greater reduction in the risk of ischemic stroke than lower dose edoxaban, and the FDA approved higher dose edoxaban in patients with creatinine clearance ≤95mL/min. This study evaluated the economic value of higher dose edoxaban vs warfarin based on data from patients in ENGAGE within the FDA-approved population.
  
  
  METHODS
  We assessed the cost-effectiveness of edoxaban vs warfarin over a lifetime horizon from the US healthcare system perspective using a Markov model based on a combination of ENGAGE AF-TIMI 48 trial data, US life tables, and published literature on the costs and long-term outcomes of non-fatal cardiovascular and bleeding events. Data from the ENGAGE AF-TIMI 48 trial were used to calculate age-adjusted event rates for warfarin and hazard ratios (HRs) for the relative impact of edoxaban on embolic and bleeding complications. Based on the wholesale acquisition price, edoxaban and warfarin were assumed to cost $9.24 and $0.36/day, respectively.
  
  
  RESULTS
  For edoxaban vs warfarin, lifetime incremental costs and QALYs were $16,384 and 0.444, respectively, yielding an incremental cost-effectiveness ratio (ICER) of $36,862/QALY gained, using data from patients with creatinine clearance ≤95mL/min in ENGAGE AF-TIMI 48. ICERs were more favorable for patients without compared to those with prior warfarin use; ICERs differed minimally by CHADS2 score.
  
  
  CONCLUSIONS
  Despite its higher acquisition cost, edoxaban is an economically attractive alternative to warfarin for the prevention of stroke and SE in patients with atrial fibrillation and creatinine clearance ≤95mL/min. These results were robust to variation of key model parameters, including assumptions regarding the cost and quality-of-life impact of stroke and bleeding events, and were favorable across both CHADS2 score stroke-risk categories.
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri - Kansas City School of Medicine, Kansas City, MO. Electronic address: emagnuson@saint-lukes.org.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Magnuson
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO.
authors.forename: Katherine
authors.initials: K
authors.lastname: Vilain
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Daiichi Sankyo, Inc, Parsippany, NJ.
authors.forename: Winghan J
authors.initials: WJ
authors.lastname: Kwong
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital, Boston, MA.
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital, Boston, MA.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Ruff
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital, Boston, MA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: Saint Luke's Mid America Heart Institute, Kansas City, MO; University of Missouri - Kansas City School of Medicine, Kansas City, MO.
authors.forename: David J
authors.initials: DJ
authors.lastname: Cohen
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000191:economics; D003362:Cost-Benefit Analysis; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004617:Embolism / Q000209:etiology / Q000517:prevention & control; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D016019:Survival Analysis; D013844:Thiazoles / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban