Evaluation of 16 genotype-guided Warfarin Dosing Algorithms in 310 Korean Patients Receiving Warfarin Treatment: Poor Prediction Performance in VKORC1 1173C Carriers

Clin Ther. 2016 Dec;38(12):2666-2674.e1. doi: 10.1016/j.clinthera.2016.10.014. Epub 2016 Nov 23.

Abstract

Purpose: The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients.

Methods: The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy.

Findings: A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk). Estimated dose and actual maintenance dose correlated well overall (r range, 0.52-0.73). Mean absolute error (MAE) of the 16 algorithms ranged from -1.2 to -20.1 mg/wk. The percentage of patients whose estimated dose fell within 20% of the actual dose ranged from 1.0% to 49%. All algorithms showed poor accuracy with increased MAE in a higher dose range. Performance of the dosing algorithms was worse in patients with VKORC1 1173TC or CC than in total (r range, 0.38-0.61 vs 0.52-0.73; MAE range, -2.6 to -28.0 mg/wk vs -1.2 to -20.1 mg/wk).

Implications: The algorithms had comparable prediction abilities but showed limited accuracy depending on ethnicity, warfarin dose, and VKORC1 genotype. Further studies are needed to develop genotype-guided warfarin dosing algorithms with greater accuracy in the Korean population.

Keywords: CYP2C9; VKORC1; genotype-guided algorithm; warfarin.

MeSH terms

  • Adult
  • Algorithms
  • Anticoagulants / administration & dosage*
  • Asian People
  • Atrial Fibrillation / drug therapy
  • Brain Infarction / drug therapy
  • Cytochrome P-450 CYP2C9 / genetics
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Male
  • Vitamin K Epoxide Reductases / genetics*
  • Warfarin / administration & dosage*

Substances

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