Background Despite the well-studied safety profile of dabigatran, its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). The study assessed whether genetic factors can contribute to CKD and alter dabigatran concentration. Methods Patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110 or 150 mg have been included in the study. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Results A total of 96 patients aged 51–89 years (median age: 75 years) were evaluated. Patients on a reduced regimen of 110 mg twice a day were older (79.8 vs. 67.9, p < 0.0001) and had lower creatinine clearance (49.7 vs. 62.3 mL/min/1.73 m2, p = 0.015). Patients with the rs2244613 CC genotype had lower C/D values (70% reduction in the mean C/D vs. AA genotype, p = 0.001). Linear stepwise regression has shown the CKD epidemiology collaboration to be the only significant predictor of C/D among genetic factors and kidney function characteristics. During the median follow-up of 15 months, there were 15 bleedings in 13 patients. Conclusions Polymorphism of CES1 rs2244613 can contribute to the safety of dabigatran in patients with AF and CKD. There was no influence of the aforementioned polymorphisms of ABCB1 on dabigatran trough plasma concentrations and C/D. Kidney function is a mainstay of clinical decision-making on direct oral anticoagulant (DOAC) dose, and further knowledge should be accumulated on the role of genetic factors.

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Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

Pulmonary arterial hypertension is a condition characterized by an increase in mean pressure in the pulmonary artery. This pathology is associated with high mortality, and specific therapy for pulmonary arterial hypertension does not affect the cause of the disease and is extremely expensive. In this regard, it is especially important to study the modifiable etiological factors of pulmonary arterial hypertension. One such factor is drugs. One of the leading groups of drugs-inductors is anorexigenic drugs. It was the representatives of this group, such as aminorex, who were the first inducers of pulmonary hypertension. Moreover, this adverse reaction was so significant that it led to the withdrawal of these drugs. Currently, the leading role in the context of drug-induced pulmonary hypertension is played by such drugs as anticancer, antiviral drugs, and interferons. These drugs lead to pulmonary hypertension through various pathophysiological mechanisms. The leading measures to prevent this pathology are to limit the use of culprit medications, reduce the spread of HIV infection, since several groups of drugs can be used to treat HIV-infected patients, leading to the development of pulmonary hypertension.

Coronary artery disease (CAD) remains the leading cause of death, and its prevalence is projected to increase in the near future. Dyslipidemia is one of the most important risk factors for CAD, and special attention is currently being paid to improving approaches to its correction. In the new revision of the Russian Guidelines for the Management of Patients with dyslipidemia (2020), priorities are given to high-intensity statin therapy: new more strict target levels of low-density lipoprotein cholesterol (LDL–C) are introduced. Experts also emphasize the important role of the cholesterol fraction of non-high-density lipoproteins (non-HDL–C), primarily triglycerides, and introduce their target levels. The concept of residual risk, which remains despite effective statin therapy and achievement of the target level of LDL–C, is closely related to non-HDL–C. Here, hypertriglyceridemia is of crucial importance, contributing to an increased risk of coronary heart disease and cardiovascular mortality. Therefore, combined lipid-lowering therapy in the form of a combination of high-intensity statin and fenofibrate is an effective approach to significantly improve the prognosis and reduce the residual risk. According to research data, rosuvastatin provides a reduction in LDL–C by ≥ 50 %, has a wide range of pleiotropic effects in combination with an optimal safety profile. Fenofibrate allows you to effectively reduce the level of triglycerides and implements additional protective effects on the cardiovascular system. The logical continuation of the principle of combined lipid-lowering therapy was the appearance of a fixed combination (FC) of rosuvastatin and fenofibrate, which already has its own evidence base of studies indicating a complex and complementary effect on the disturbed blood lipid spectrum, a good safety profile of therapy, and the form of ‘single-pill’ significantly increases patients adherence to treatment. It can be expected that the widespread use of rosuvastatin and fenofibrate in clinical practice will effectively reduce the residual cardiovascular risk and thus provide an improved prognosis for patients.