Prediction of optimal warfarin maintenance dose using advanced artificial neural networks

Pharmacogenomics. 2014 Jan;15(1):29-37. doi: 10.2217/pgs.13.212.

Abstract

Background: In recent years, pharmacogenetic algorithms were developed for estimating the appropriate dose of vitamin K antagonists.

Aim: To evaluate the performance of new generation artificial neural networks (ANNs) to predict the warfarin maintenance dose.

Methods: Demographic, clinical and genetic data (CYP2C9 and VKORC1 polymorphisms) from 377 patients treated with warfarin were used. The final prediction model was based on 23 variables selected by TWIST® system within a bipartite division of the data set (training and testing) protocol.

Results: The ANN algorithm reached high accuracy, with an average absolute error of 5.7 mg of the warfarin maintenance dose. In the subset of patients requiring ≤21 mg and 21-49 mg (45 and 51% of the cohort, respectively) the absolute error was 3.86 mg and 5.45 with a high percentage of subjects being correctly identified (71 and 73%, respectively).

Conclusion: ANN appears to be a promising tool for vitamin K antagonist maintenance dose prediction.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Cytochrome P-450 CYP2C9
  • Dose-Response Relationship, Drug
  • Drug Dosage Calculations*
  • Female
  • Humans
  • International Normalized Ratio
  • Male
  • Neural Networks, Computer
  • Polymorphism, Genetic
  • Vitamin K / administration & dosage
  • Vitamin K / antagonists & inhibitors*
  • Vitamin K Epoxide Reductases / genetics
  • Warfarin / administration & dosage*

Substances

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