Atrial fibrillation (AF) accounts for 40% of all cardiac arrhythmias and is associated with a high risk of stroke and systemic thromboembolic complications. Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that have been proven to prevent stroke in patients with non-valvular AF. This review summarizes the pharmacokinetics, pharmacodynamics, and drug interactions of DOACs, as well as new data from pharmacogenetic studies of these drugs. This review is aimed at analyzing the scientific literature on the gene polymorphisms involved in the metabolism of DOACs. We searched PubMed, Cochrane, Google Scholar, and CyberLeninka (Russian version) databases with keywords: ‘dabigatran’, ‘apixaban’, ‘rivaroxaban’, ‘edoxaban’, ‘gene polymorphism’, ‘pharmacogenetics’, ‘ ABCB1’, ‘ CES1’, ‘ SULT1A’, ‘ ABCG2’, and ‘ CYP3A4’. The articles referred for this review include (1) full-text articles; (2) study design with meta-analysis, an observational study in patients taking DOAC; and (3) data on the single-nucleotide polymorphisms and kinetic parameters of DOACs (plasma concentration), or a particular clinical outcome, published in English and Russian languages during the last 10 years. The ages of the patients ranged from 18 to 75 years. Out of 114 reviewed works, 24 were found eligible. As per the available pharmacogenomic data, polymorphisms affecting DOACs are different. This may aid in developing individual approaches to optimize DOAC pharmacotherapy to reduce the risk of hemorrhagic complications. However, large-scale population studies are required to determine the dosage of the new oral anticoagulants based on genotyping. Information on the genetic effects is limited owing to the lack of large-scale studies. Uncovering the mechanisms of the genetic basis of sensitivity to DOACs helps in developing personalized therapy based on patient-specific genetic variants and improves the efficacy and safety of DOACs in the general population.

Background: Stroke is a problem worldwide because of its high mortality and disability rates. Almost 90% of strokes are ischemic, and more than half of the deaths are caused by an ischemic stroke. Most risk factors for stroke are manageable so that it can be avoided with proper prevention. Despite the success in determining the causes of stroke in recent years, selectively, the “culprit” causing stroke remains unsolved. In such cases, a diagnosis of undetermined etiology (cryptogenic stroke) or embolic stroke of undetermined source (ESUS) is generated, resulting the prevention of a recurrent cerebrovascular occurrence impossible. Atrial fibrillation (AF) can be a cause of stroke by causing blood clots in the chambers of the heart. Purpose: The aim was to determine the optimal method of heart rate monitoring in patients with ischemic stroke, as methods and approaches for detecting AF are very diverse, but there is still no single opinion, which would be universal. Procedures: In our review, we consider epidemiology, risk factors for the stroke of undetermined etiology, as well as analytical methods for detecting heart rhythm disturbances in this category of patients. Findings: Atrial fibrillation (AF) is detected by thorough monitoring of heart rate of patients with cryptogenic stroke and ESUS can be diagnosed in up to 46% of patients. Conclusion: After AF detection, consideration should be given to prescribing anticoagulants, instead of antiplatelet agents, for the secondary prevention of stroke.

Background : Allelic variants of genes encoding enzymes of the esterase system ( CES1 ) and P-glycoprotein ( ABCB1 ) can change the metabolism and pharmacokinetics of dabigatran. Therefore, they act as determining factors in the development of side effects, especially bleeding. We analyzed the genotype-phenotype relationship of ABCB1 (rs1045642, rs4148738, rs2032582, and rs1128503) and CES1 (rs8192935, rs71647871, and rs2244613) polymorphisms in patients with atrial fibrillation who had been treated with dabigatran. Methods: A total of 150 patients were recruited for this study. TaqMan technology was used for SNP genotyping. Results: Patients with the rs2244613 GG genotype had a lower concentration (55.27 +/- 34.22 ng/ml) compared to those with the TT genotype (63.33 +/- 52.25 ng/ml) (additive model, P = 0.000). Individuals with the rs8192935 AA genotype had a lower concentration (52.72 +/- 30.45 ng/ml) compared to those with the GG genotype (79.78 +/- 57 ng/ml) (additive model, P = 0.001). The APTT values among the different genotypes of the ABCB1 SNPs, rs4148738 and rs1045642, were significantly different (P = 0.035 and P = 0.024, respectively). Conclusion : Our research demonstrates that the CES1 polymorphisms, rs8192935 and rs2244613, are associated with the pharmacodynamics and pharmacokinetics of dabigatran in the Kazakh subpopulation.

Objective: Atrial fibrillation is strongly associated with stroke and accounts for 60% of cardioembolic stroke. Assessing thromboembolic risk is important for patients with atrial fibrillation. Approximately 90% of all thrombus are localized in the left atrium appendage (LAA). This study aimed to determine the efficacy of cardiac computed tomography (CT) for LAA thrombus detection. Material and methods: This retrospective study included 292 patients. LAA thrombus was confirmed or excluded by cardiac CT with the reference to transesophageal echocardiography (TEE). We excluded patients with allergic reactions to iodide, increased creatinine levels, thyroid disease (hyperthyroidism), pregnancy, and age <18 years. Results: According to the cardiac CT, 103 of 292 people had LAA thrombus, while according to TEE, only 48 of patients had LAA thrombus. The sensitivity and specificity of CT were 97.7% and 77%, respectively. The sensitivity and specificity of the CT was higher in 2016–2020, when the delayed phase was added to the standard protocol, compared to 2012–2015 years. Older age, higher BMI, higher CHA2DS2-VASc and HAS-BLED scores, and larger LA and LVESV were significantly associated with LAA thrombus detection on cardiac CT. Higher LVESV and LVEDV indexes (LVESVI and LVEDVI) and lower LV ejection fraction measured by TEE were also predictors of LAA thrombus detection by cardiac CT. Conclusion: Our findings show that cardiac CT has high sensitivity and specificity for excluding or confirming LAA thrombus, and can also be exclusively used to determine the presence or absence of a thrombus.