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An acenocoumarol dose algorithm based on a South-Eastern European population

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Aim

To develop and validate an algorithm for the prediction of therapeutic dose of acenocoumarol in Romanian patients.

Methods

The inclusion criteria for entry to the study was age ≥18 years and starting acenocoumarol treatment for at least one of the following clinical indications: acute deep vein thrombosis of the lower limbs, persistent or permanent atrial fibrillation, and/or the presence of valvular prostheses requiring prolonged oral anticoagulant therapy. The patients were followed up for 3 months. Patients admitted to the internal medicine, cardiology, and geriatrics wards of the Municipal Clinical Hospital, Cluj-Napoca and “Niculae Stăncioiu” Heart Institute between October 2009 and June 2011 who fulfilled the inclusion criteria were included in the study. Clinical and demographic data that could influence the acenocoumarol stable dose were recorded for each patient. Genetic analysis included the genotyping the CYP2C9*2 and *3, and the VKORC1 -1693 G > A polymorphisms. The patients were randomly divided into two groups: (1) the main group on which the development of the clinical and genetic algorithms for acenocoumarol dose prediction was based; (2) the validation group.

Results

The study included 301 patients, of whom 155 were women (51.5 %) and 146 were men (48.5 %). The median age of the patient cohort was 66 (women, 57; men, 73) years. After randomization the main group comprised 200 patients (66.4 %) and the validation group 101 patients (33.6 %). Age and body mass index explained 18.8 % (R 2) of the variability in acenocoumarol weekly dose in patients in the main group. When the genetic data were added to the algorithm, the CYP2C9*2 and *3 polymorphisms and the VKORC1 -1693 G > A polymorphism accounted for 4.7 and 19. 6 % of acenocoumarol dose variability, respectively. For the main group, we calculated a mean absolute error of 5 mg/week (0.71 mg/day). In the validation group, clinical parameters explained 22.2 % of the weekly acenocoumarol dose variability. Genetic polymorphisms increased the R 2 coefficient to 32.8 %.

Conclusion

We have developed and validated an accurate algorithm for prediction of the stable therapeutic dose of acenocoumarol in a Romania population.

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Acknowledgments

This study was supported by research grant 42-127/2008 “Trombo-Gen”, from National Authority for Scientific Research from Romania.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. 5th Department of Surgery, Municipal Hospital of Cluj-Napoca, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 11th Tăbăcarilor Street, 400139, Cluj-Napoca, Cluj, Romania

    Tudor Radu Pop

  2. Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 6th Pasteur Street, 400349, Cluj-Napoca, Cluj, Romania

    Ştefan Cristian Vesa & Anca Dana Buzoianu

  3. Department of Medical Genetics, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 6th Pasteur Street, 400349, Cluj-Napoca, Cluj, Romania

    Adrian Pavel Trifa

  4. 5th Department of Internal Medicine, Municipal Hospital of Cluj-Napoca, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 11th Tăbăcarilor Street, 400139, Cluj-Napoca, Cluj, Romania

    Sorin Crişan

Authors
  1. Tudor Radu Pop
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  2. Ştefan Cristian Vesa
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  3. Adrian Pavel Trifa
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  5. Anca Dana Buzoianu
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Correspondence to Ştefan Cristian Vesa.

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Pop, T.R., Vesa, Ş.C., Trifa, A.P. et al. An acenocoumarol dose algorithm based on a South-Eastern European population. Eur J Clin Pharmacol 69, 1901–1907 (2013). https://doi.org/10.1007/s00228-013-1551-3

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  • DOI: https://doi.org/10.1007/s00228-013-1551-3

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