ASSESSMENT OF BLEEDING RISK FACTORS DURING WARFARIN THERAPY IN ISCHEMIC HEART DISEASE COMPLICATED BY ATRIAL FIBRILLATION
DOI:
https://doi.org/10.11603/mcch.2410-681X.2022.i2.13202Keywords:
Warfarin, anticoagulant therapy, atrial fibrillation, coronary heart disease (CHD), bleeding, geneticsAbstract
Introduction. Anticoagulant therapy is necessary for patients with atrial fibrillation. Each of the drugs has its own characteristics, which are particularly pronounced in Warfarin. This is the drug with a narrow therapeutic window and sensitivity to the influence of various factors on its pharmacokinetics and pharmacodynamics.
The aim of the study – to analyze the influence of modifying factors on the effectiveness of treatment according to the literature data, in particular, the characteristics of nutrition, lifestyle and following the religious canons (fasting), bad habits, drug interaction, in order to minimize their influence on the results of the study and to assess the role of constant factors (age, gender, the presence of a genetic mutation of CYP2C9, concomitant pathology, bleeding in the anamnesis) on the effectiveness and safety of Warfarin.
Research Methods. 100 patients participated in the study. They had general clinical, instrumental, pharmacogenetic examinations: the identification of polymorphic alleles Arg144Cys of the CYP2C9*2 gene and Ile359Leu of the CYP2C9*3 gene was carried out by the PCR method. These options are associated with a higher risk of bleeding. Statistical processing included: assessment of the conformity of the distribution of genotypes with expected values according to the Hardy-Weinberg equilibrium; determination of intergroup probable difference of quantitative values – calculated by T-test for independent samples by groups and % – by the χ2 criterion.
Results and Discussion. Among all the unmodified factors listed above, the variant of individual pharmacogenetics had the most powerful influence. The dependence of hemorrhagic complications on the presence of altered (mutant) alleles of detoxification enzymes CYP2C9 was established with high reliability. A total of 34 patients had hemorrhagic complications during the study, 8 of them – twice, one – three times. 30 cases of mutations of all types were identified. Among carriers of the mutant allele, 24 patients (70.6 %) had bleeding versus 6 patients (9.1 %) without the mutation, p<0.0001. In heterozygotes (S/T) of both types of mutation, 14 patients (41.2 %) had hemorrhagic complications against 6 (9.1 %), p<0.0001. In homozygotes of both types (T/T mutations), bleeding was observed in 11 patients (32.4 %), versus 0 (0) in the group with unchanged alleles, p<0.0001; since both alleles have an amino acid substitution, the metabolism of drugs dependent on CYP2C9, in our case Warfarin, slows down, which leads to a higher concentration of it in the blood and the risk of bleeding.
Conclusion. The research and implementation of the patient's individual genetic passport may be a promising direction to ensure the effectiveness and safety of Warfarin therapy.
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