Evaluation of pharmacogenetic algorithm for warfarin dose requirements in Japanese patients

Circ J. 2010 May;74(5):977-82. doi: 10.1253/circj.cj-09-0876. Epub 2010 Mar 26.

Abstract

Background: Warfarin dosing is difficult to establish because of considerable interindividual variation. Thus, warfarin pharmacogenetics have attracted particular interest in relation to appropriate control of anticoagulation.

Methods and results: The 200 eligible subjects were chosen from participants in a hospital cohort. Performance of a pharmacogenetic algorithm recently developed by the International Warfarin Pharmacogenetics Consortium (IWPC) was tested and compared with a clinical algorithm (without genotype data) by calculating the percentage of patients for whom the predicted dose deviated by less than 7 mg/week (1 mg/day) from the actual dose. The pharmacogenetic algorithm accurately identified a significantly (P<0.05) larger proportion of patients to achieve the target international normalized ratio than did the clinical algorithm (68% vs 36% for a low-dose group; and 21% vs 0% for a high-dose group). Also, an increase in warfarin dosage was found to be appropriate for the current status of alcohol drinking (4 mg/week, as against non-drinking) and smoking (3.3 mg/week, as against non-smoking).

Conclusions: The IWPC pharmacogenetic algorithm has clinical application, particularly in identifying Japanese patients who require a low dosage of warfarin and are at greater risk of excessive anticoagulation.

Publication types

  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alcohol Drinking
  • Algorithms*
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Asian Continental Ancestry Group
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / ethnology
  • Cardiovascular Diseases / genetics
  • Cohort Studies
  • Cytochrome P-450 CYP2C9
  • Female
  • Genotype
  • Humans
  • International Normalized Ratio*
  • Japan
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics
  • Pharmacogenetics / methods
  • Polymorphism, Genetic
  • Smoking
  • Vitamin K Epoxide Reductases
  • Warfarin / administration & dosage*
  • Warfarin / adverse effects

Substances

  • Anticoagulants
  • Warfarin
  • Mixed Function Oxygenases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Vitamin K Epoxide Reductases