Universal versus genotype-guided use of direct oral anticoagulants in atrial fibrillation patients: a decision analysis

Pharmacogenomics. 2015;16(10):1089-100. doi: 10.2217/pgs.15.64. Epub 2015 Jul 31.

Abstract

Aim: This study aims to compare clinical and economic outcomes of CYP2C9 and VKORC1 genotype-guided (PG-DOAC) versus universal use of direct oral anticoagulant (DOAC) for stroke prevention in patients with atrial fibrillation (AF).

Methods: Outcomes of oral anticoagulation therapy were simulated using life-long Markov modeling. In PG-DOAC, patients with genotype of high or low warfarin sensitivity were treated with DOAC, and patients with normal warfarin sensitivity genotype received warfarin.

Results: Expected quality-adjusted life-years (QALYs) and cost of DOAC were higher than PG-DOAC. Incremental cost per QALY (ICER) of DOAC versus PG-DOAC was 314,129 USD/QALY, exceeding willingness-to-pay threshold (50,000 USD/QALY).

Conclusion: Using individual genotype to guide the use of DOAC versus warfarin appears to be the preferred strategy.

Keywords: CYP2C9; VKORC1; atrial fibrillation; cost–effectiveness analysis; direct oral anticoagulant; genotype-guided therapy; warfarin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / therapeutic use*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / genetics*
  • Cost-Benefit Analysis / methods
  • Cytochrome P-450 CYP2C9 / genetics
  • Decision Support Techniques
  • Genotype
  • Humans
  • Markov Chains
  • Quality-Adjusted Life Years
  • Stroke / genetics
  • Stroke / prevention & control
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / therapeutic use

Substances

  • Anticoagulants
  • Warfarin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases