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Estimation and validation of acenocoumarol dosing algorithms in Bulgarian patients with cardiovascular diseases

Reni Tzveova1, Antoaneta Dimitrova-Karamfilova2, Radoslava Saraeva1

  • 1Molecular Medicine Center, Department of Medical Chemistry & Biochemistry, Medical Faculty, Medical University - Sofia, 2 Zdrave str, Sofia 1431, Bulgaria.

Personalized Medicine
|May 18, 2018
PubMed

Insights

Genetic factors like VKORC1-1639G>A and CYP2C9 variations, along with age and diagnosis, significantly influence acenocoumarol dose variability in Bulgarian patients. These findings led to validated prediction algorithms for stable anticoagulant dosing.

Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Genomics

Background:

  • Acenocoumarol dosing requires individualization due to significant inter-patient variability.
  • Genetic polymorphisms in CYP2C9 and VKORC1 are known to influence acenocoumarol metabolism and response.
  • Understanding these factors is crucial for optimizing anticoagulant therapy.

Purpose of the Study:

  • To investigate the impact of genetic (CYP2C9*2, *3, VKORC1-1639G>A, VKORC11173C>T) and non-genetic factors on acenocoumarol dose variability.
  • To develop and validate predictive algorithms for stable acenocoumarol dosing in the Bulgarian population.
  • To identify key determinants of acenocoumarol dose variability.

Main Methods:

  • Genotyping of 169 Bulgarian patients for specific CYP2C9 and VKORC1 gene variants.
  • Analysis of genetic and non-genetic factors influencing acenocoumarol dose in a derivation cohort.
  • Validation of developed algorithms in a separate test cohort.

Main Results:

  • VKORC1-1639G>A (25.5%), CYP2C9*2 (7.8%), CYP2C9*3 (6.1%), age (13.6%), and diagnosis (6.0%) were significant predictors of acenocoumarol dose variability.
  • Genetic and clinical models explained 46.5% and 23.0% of dose variability, respectively.
  • Factors like sex, weight, and amiodarone use showed limited impact on dose variability.

Conclusions:

  • Validated clinical and pharmacogenetic algorithms were developed for predicting stable acenocoumarol doses.
  • These algorithms are specifically tailored for the Bulgarian population.
  • The study highlights the importance of integrating genetic and clinical information for personalized anticoagulant therapy.

Keywords:
Bulgarian populationCYP2C9VKORC1acenocoumarolpharmacogenetic algorithm

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