Cost-Effectiveness of High-Dose Edoxaban

Study Questions:

Does high-dose edoxaban offer economical advantages over adjusted-dose warfarin in patients with nonvalvular atrial fibrillation (NVAF)?


The authors constructed a Markov model, which relies on an assumed current state and not on events that happened previously, to estimate the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of high-dose edoxaban (60 mg dose) with adjusted-dose warfarin in patients with NVAF. The hypothetical cohort was a 70-year-old patient with NVAF, a mean CHADS2 score of 3, creatinine clearance of 15-95 ml/minute, and no prior contraindication to anticoagulation. Data were obtained from the renal subgroup analysis of ENGAGE-AF (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation) and other published trials, and a 10,000-iteration probabilistic sensitivity analysis was used to test the model’s robustness.


Using a hypothetical cohort and a lifetime horizon maximum follow-up of 30 years, the QALY results were 10.11 and 10.50 for warfarin and edoxaban, respectively (increase of 0.39 for patients on edoxaban). Total costs for those receiving warfarin equaled $123,516, and total costs for those receiving edoxaban equaled $99,833 (a difference of $23,683). The results continued to favor edoxaban when the model was rerun for various time horizons, including 2.8 (the median follow-up time in the ENGAGE-AF trial), 5, 10, and 20 years. The 10,000-iteration probabilistic sensitivity analysis found edoxaban to be the economically dominant strategy >99% of the time. The results were most sensitive to the cost of high-dose edoxaban (wholesale acquisition cost), cost of intracranial hemorrhage (ICH)-related neurological impairment, cost of adjusted-dose warfarin (wholesale acquisition cost), and utility of edoxaban. However, varying these factors did not affect the model’s conclusion.


Edoxaban offers economical advantages over warfarin in patients with NVAF, including increased QALYs, decreased costs, and cost-effectiveness. This is the first study to demonstrate the cost-effectiveness of edoxaban over warfarin from a U.S. perspective.


The findings from this study are consistent with similar studies of other direct oral anticoagulants. The reduced risk of developing debilitating ICH with direct oral anticoagulants, compared with warfarin, is likely a major contributor to the observed improvement in QALYs and overall cost-effectiveness. It is important to note, however, that this analysis used data from clinical trials whose probability models are based on hypothetical scenarios, which may not extrapolate to the real world. Nevertheless, appropriate clinical use of any anticoagulant is necessary to achieve such favorable economical outcomes.

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