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The paper presents the results of evaluating the genetic and cytogenetic toxicity of etoposide, as well as the evaluation results of protective properties of aspirin against the toxicity of etoposide in C57Bl/6J mice. The cytogenetic activity and protective properties assessment was carried out using the chromosome aberration analysis in metaphase cells. Etoposide was tested at a concentration of 15 and 3 mg/kg and aspirin — at a concentration of 25 mg/kg of the animal. The results of metaphase analysis showed that etoposide exhibits cytogenetic toxicity in both doses, and aspirin exhibits protective properties against the toxicity of etoposide at a concentration of 15 mg/kg. The results of chromosome analysis regarding the protective properties of aspirin against etoposide at a concentration of 3 mg/kg are ambiguous and require further experiments.

Background. In our previously published studies, we demonstrated a high hemostatic activity of a low dose of exogenous fibrin monomer during its systemic administration in a model of dosed liver injury with preliminary inhibition of platelet aggregation. However, the analysis of platelet involvement in the mechanisms of local fibrin formation has not been analyzed. The aim of the study. To conduct a comparative analysis of the cellular composition of venous and wound blood, as well as blood in the wound vessels to assess the contribution of platelets to the hemostatic effect of exogenously administered fibrin monomers in dosed liver injury under conditions of pharmacologically determined thrombocytopathy. Methods. In a model of dosed liver injury in rabbits after inhibition of platelet aggregation by acetylsalicylic acid in combination with clopidogrel, the effect of the administration of fibrin monomer was evaluated in comparison with the use of tranexamic acid. We studied the number of platelets in venous and wound blood smears, as well as in the contents of wound vessels. Results. It has been established that with the systemic administration of exogenous fibrin monomer, the number of platelets in wound blood smears decreases by 17.2 % in comparison with free circulating venous blood. Platelets in wound blood form aggregates and are in an activated state. In the wound vessels, the number of these cells was maximum (150 per lower field) compared with the number of platelets in the placebo and tranexamic acid groups (55 and 84 per lower field, respectively). Also in the wound blood, erythrocytes with altered forms (echinocytes, schistocytes, stomatocytes and ovalocytes) were found. Conclusion. Systemic administration of exogenous fibrin monomer affects the redistribution of platelets between the systemic circulation, wound vessels and wound blood, determining its hemostatic effect and local wound fibrin formation in dosed liver injury. The presence of receptor-mediated platelets recruitment due to fibrin monomer in the wound vessels with the participation of damaged erythrocytes is assumed.

Introduction. Acetylsalicylic acid (ASA, aspirin) resistance is the inability to reduce thromboxane A2 synthesis in platelets and inhibit platelets activation and aggregation while taking ASA. Assessment of urinary 11-dehydrothromboxane B2 (11-dhTxB2) levels is one of the methods to identify aspirin resistance. Our research aimed to investigate whether urinary 11-dhTxB2 levels and other clinical and laboratory parameters are associated with a history of major adverse cardiovascular events (MACE) including myocardial infarction and ischaemic stroke in aspirin-treated patients with stable coronary artery disease. Patients and methods. In a cross-­sectional study we investigated 82 patients with stable coronary artery disease who took ASA at doses of 75–150 mg/day. We used the evaluation of the urinary 11-dhTxB2 levels standardized by creatinine as a method to identify aspirin resistance. Statistical analysis was performed using Mann-­Whitney U-test, ROC-analysis and multivariable logistic regression. Results. The medians of urinary 11-dehydrothromboxane B2 level in patients with and without MACE were 587.8 (Q1-Q3 512.8–800.3) pg/mg creatinine and 438.3 (Q1–Q3 337.6–577.9) pg/mg creatinine, respectively (p=0.001). The threshold level of urinary 11-dhTxB2, which predicted a high risk of aspirin resistance, was 521.1 pg/mg creatinine, and in 36 (43.9 %) patients the concentration of the 11-dhTxB2 exceeded this level. The regression model characterising the dependence of the presence of a history of MACE was constructed. It included platelet count, urinary levels of 11-dhTxB2 and the presence of type 2 diabetes. Sensitivity and specificity of the model were 55 % and 88.9 %, respectively. Conclusions. The results of the study demonstrate that the antiplatelet effect of aspirin is weaker in stable coronary artery disease patients with a history of MACE than in those without a history of MACE.

Background. Preeclampsia (PE) complicates 28% of pregnancies worldwide, negatively impacting the pregnant woman and the fetus. Therefore, its prevention remains relevant. It is believed that the cause of PE, especially early PE, is a placentation disorder. It warrants studying drugs that can improve placenta development. The leadership in this matter is maintained by acetylsalicylic acid, which, according to the ASPRE study, reduced the incidence of PE at 34 weeks of pregnancy by 82%. The use of low molecular weight heparins (LMWH), dipyridamole, and antioxidants for PE prevention remains controversial and continues to be studied by foreign and Russian scientists. Aim. To assess the efficacy of acetylsalicylic acid, LMWH, dipyridamole (Curantyl), and bovine blood derivates (Actovegin) in the Russian population of pregnant women at high risk for PE prevention. Materials and methods. The study included 244 patients. We reviewed the archived case records of 103 patients diagnosed with severe PE, who delivered in 2019 at the State Clinical Hospital №24, and 141 pregnant women from the Maternity clinic №3 at the Veresaev Moscow State Clinical Hospital, where the risk of PE was assessed as high, according to the results of extended combined screening of the first trimester of pregnancy. Eighty-nine pregnant women received acetylsalicylic acid at a dose of 75 mg and 54 at a dose of 150 mg. In addition, 22 patients received LMWH, 6 dipyridamole, and 3 Actovegin. The absolute risks, the risk ratio, and statistical significance when taking drugs in each risk group were calculated to assess the efficacy of acetylsalicylic acid and other drugs for PE prevention in the above risk groups. Results. The resulting weak inverse correlation (r=-0.31) between the PE severity at delivery and the dose of acetylsalicylic acid indicates that an increase in the acetylsalicylic acid dose was associated with a decrease in the PE severity. The effectiveness of combinations of various drugs for PE prevention was assessed by analyzing factor correspondences. Two-dimensional scaling of the most likely combinations showed that most patients received acetylsalicylic acid in the high-risk group with no PE. Additional use of LMWH, Curantyl, and Actovegin did not reduce the risk of PE. Conclusion. Acetylsalicylic acid is the only pharmaceutical method for preventing PE in high-risk groups. Higher doses of acetylsalicylic acid are associated with lower PE severity.

Background. The patients who require major lower limb joint replacement have a high prevalence of comorbidities, particularly hypertension. Also, they are mostly elderly, with concomitant obesity, chronic kidney disease, poor glycemic control, etc. These factors individually and collectively increase the risk of complications in the perioperative period. Aim. To study the features of preoperative drug therapy for cardiovascular diseases considering the indications in patients hospitalized for elective major lower limb joint replacement. Materials and methods. The study included an unselected sample of patients, 41 males and 77 females (n=118). The mean age was 64.711.1 years, and the mean body mass index was 30.74.9 kg/m2. All patients had a detailed history, an examination with blood pressure measurement, and their therapy for cardiovascular diseases was analyzed. Of 118 patients, 88 (74.6%) had hypertension, 68 (77.2%) received angiotensin-converting enzyme inhibitors, 20 (22.8%) angiotensin receptor blockers, 17 (19.3%) calcium channel blockers combined with other antihypertensive drugs, 11 (12.5%) had no antihypertensive therapy before hospitalization, despite a recorded high blood pressure for several years. Results. The routine preoperative outpatient examination included lipid profile in 77 (65.3%) patients, most of whom had total cholesterol only (66 had levels above normal); low-density lipoprotein levels were measured in only 14 (11.9%) patients, and 9 had levels above target for the relevant risk group. Statins were previously prescribed to only 18 (15.3%) patients. Twenty-two (18.6%) patients reported taking acetylsalicylic acid, with only 7 according to indications; 5 (4.2%) received clopidogrel, of which 1 patient had no indications. Conclusion. Most of the study patients had hypertension of varying severity. Some patients received suboptimal antihypertensive therapy and, in some cases, previously prescribed antihypertensive drug combinations not complying with relevant guidelines. Most patients with hypercholesterolemia did not receive statins with no rationale for not prescribing this class of drugs. Some patients received antiplatelet agents with no appropriate indications.

Objective: to assess the clinical and economic feasibility of ticagrelor in combination with acetylsalicylic acid (ASA) in comparison with clopidogrel in combination with ASA in patients with acute coronary syndrome (ACS), including both those who underwent, and those who did not undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG); and new oral anticoagulants (NOACs) in combination with clopidogrel in comparison with warfarin in combination with clopidogrel and ASA in patients with atrial fibrillation (AF) who underwent PCI; to identify the impact of the above strategies of antithrombotic therapy on the targets of the State Health Care Program of the Russian Federation (RF) “Development of Health Care” and the Federal Project “Cardiovascular Diseases Control”.Material and methods. The clinical and economic study (CES) of ticagrelor in combination with ASA in ACS patients was based on a costbenefit analysis. A combined model, including a decision tree and Markov model was developed. The horizon period of the analysis was 5 years. Quality-adjusted life year (QALY) was used as an efficiency criterion and only the direct medical costs associated with the conditions identified in the modeling were taken into account. A discount rate of 5% was taken into account during the CES. The application of NOACs in combination with clopidogrel was studied in the CES using a cost minimization analysis considering the costs per patient characterized by the presence of AF regardless of the presence of ACS and a history of PCI.Results. We used a decision tree and Markov modeling in adult patients with ACS, who had or had not undergone PCI or CABG, in the horizon period of 5 years considering the discount rate of the added quality-adjusted life year (incremental cost-effectiveness ratio (ICER) per QALY). The result for ticagrelor in combination with ASA compared to clopidogrel in combination with ASA was 605,199 rubles, which was significantly lower than the willingness-to-pay threshold (2,235,201 rubles). Assessment of the impact of the therapy regimen including ticagrelor in combination with ASA on the target indicators of the State Health Care Program of the RF “Development of Healthcare” and the Federal Project “Cardiovascular Diseases Control” showed that the use of this therapy regimen will reduce mortality from myocardial infarction (MI) and cardiovascular causes by 2.45 cases per 100 thousand population provided that 100% of patients with MI and unstable angina in the RF are transferred from clopidogrel + ASA scheme to ticagrelor + ASA. The potential contribution of ticagrelor in combination with ASA compared to clopidogrel in combination with ASA in patients with ACS in achieving the target reduction of mortality from circulatory diseases will be 6.48% by 2023. In all simulated scenarios, in the group of patients with AF who had undergone PCI, pharmacotherapy regimens containing NOACs (dabigatran etexilate, rivaroxaban, apixaban) were more costly than therapy regimens containing warfarin (with not significantly different effectiveness).Conclusion. The results of the evaluation of clinical and economic feasibility of antiplatelet therapy strategies demonstrated the costeffectiveness of ticagrelor in combination with ASA compared to clopidogrel in combination with ASA in patients with ACS, including those who had undergone PCI or CABG and those who had not. The strategy of ticagrelor + ASA showed a favorable effect on the rates of mortality from MI, as well as from circulatory diseases. The results of the clinical and economic evaluation of the four strategies of antithrombotic drug therapy in patients with AF who had undergone PCI showed higher costs of the regimens containing NOACs with a presumed zero effect on the mortality from circulatory diseases.

Antiplatelet agents are an integral part of the treatment of patients with various presentations of atherothrombosis. Among all drugs in this group, acetylsalicylic acid has the broadest evidence base. This review is devoted to the prescription of acetylsalicylic acid for the primary prevention of vascular complications in patients without clinically apparent atherosclerosis. Current approaches to the risk stratification of ischemic events and determination of indications for such treatment are discussed. Primary prevention trials have been focused on the risk assessment scales, the prognostic value of which raises many questions. In this context, besides the traditional (classical) factors underlying these scales, it is reasonable to take into account the so-called “risk modifiers” that can affect the likelihood of CVC. The coronary artery calcium score is one of the strongest risk modifiers. The characteristics of key primary prevention trials, which included patients of different ages with various risk factors, are provided. In accordance with the current guidelines of European and Russian expert communities, the acetylsalicylic acid may be prescribed to individuals with a high risk of vascular complications, among which the best evidence base is available for patients with diabetes mellitus. The positive effects of antiplatelet treatment have been demonstrated to be maintained in the settings of modern therapy with a proven positive effect on the prognosis. A particular focus has been placed on minimizing bleeding. The correct assessment and correction of modifiable hemorrhagic risk factors, the use of drugs to protect the stomach, and the appointment of acetylsalicylic acid in the minimum effective dosage of 75 mg per day are called upon to increase the safety of treatment. A preference in favour of uncoated forms that are absorbed in the stomach for obese and diabetic patients may be discussed.

One of the most important aspects of reducing the incidence of preeclampsia is the most complete and timely assessment of risk factors for each patient. One of the well-known, but often overlooked, risk factors is a family history of preeclampsia. In the history of our patient during her first pregnancy the fact of her mother’s eclampsia was ignored, antithrombotic medication were not prescribed, and the pregnancy has ended in premature birth due to severe preeclampsia. The examination confirmed inherited thrombophilia – Leiden mutation. The next pregnancy was managed with appointment of antithrombotic medication – low molecular weight heparin and low doses of acetylsalicylic acid, without complications and ended in timely delivery.

Cerebral circulation disorders (CCD) are one of the most common causes of mortality and disability in the population. Improving the microcirculation of brain tissue is one of the main directions in the treatment and prevention of CCD.Aim of the study was to evaluate the effect of a new derivative of hydroxybenzoic (salicylic) acid on neurological deficit, hemostasis and functional state of arterial pial vessels in the study of prostacyclin-synthetic activity and evaluation of NOmediated endothelial dysfunction in rats under experimental CCD conditions. Material and methods. The experiment was carried out on 50 Wistar rats, which were simulated for CCD by occlusion of common carotid arteries. Within 7 days after the operation, the animals received treatment according to the group: saline, C-60 (N-(3-hydroxybenzoyl)taurine dipotassium salt) and acetylsalicylic acid. After treatment, the activity of the prostacyclin-synthetic system was assessed by the reaction of pial vessels to indomethacin, endothelial dysfunction was estimated by tests with acetylcholine and L-NAME. The parameters of plasma and platelet hemostasis were also studied, and behavioral tests (open field, adhesion test, rotarod, Morris water maze, passive avoidance task) were used to assess neurological deficits in animals. Results. When studying the level of neurological deficit in animals with brain ischemia after a course of administration of the test compound, it was noted that in the treated groups, compared with the control group, there was a significant increase in motor and exploratory activity, improvement in sensory-motor function and coordination of movements (p < 0.05). Also, in the group treated with the salicylic acid derivative, normalization of the parameters of platelet and plasma hemostasis, improvement of the functional state of the vascular endothelium was observed. According to the results of assessing the prostacyclin-synthesizing activity of the endothelium of the cerebral vessels, it follows that the test compound inhibits cyclooxygenase at a level comparable with effect of acetylsalicylic acid. Conclusions. A new derivative of salicylic acid, the dipotassium salt of N-(3-hydroxybenzoyl)taurine, reduces the severity of neurological deficit, improves hemostasis parameters and the functional state of cerebral vessels in rats with brain ischemia in the experiment.

Objectives: to evaluate the clinical effectiveness of the Metida for the prevention of perinatal pathology in pregnant women with gestational endotheliopathy and with the risk of preeclampsia. Materials and methods. 68 pregnant women with verified gestational endotheliopathy and with risk of preeclampsia > 1:150 participated in a prospective clinical comparative study. The patients were divided into subgroups: the first subgroup included 30 women who from 11–13 weeks of pregnancy received acetylsalicylic acid 100 mg/day and vitamin D 2000 IU/day; the II subgroup included 38 pregnant women who from 11–13 weeks of gestation received acetylsalicylic acid 100 mg/day, vitamin D 2000 IU/day and Metida (300 mg of elemental magnesium, 30 mg of vitamin B6). 28 practically healthy pregnant women of the control group received vitamin D 1000 IU/day. The clinical effectiveness of therapy was evaluated by comparing the number of cases of perinatal pathology; cases of intrauterine suffering of the fetus; the dynamics of indicators of laboratory-instrumental research methods (markers of the risk of perinatal pathology) and the pregnancy outcomes. Results. Metida as an additional preventive therapy made it possible to significantly reduce the number of cases of placental dysfunction (р = 0.01) and intrauterine suffering of the fetus (р = 0.02) compared to standard preventive therapy. There was also a 6-fold reduction in the incidence of preeclampsia and premature birth due to magnesium supplementation, compared to pregnant women who received only acetylsalicylic acid and vitamin D. There was a significant decrease in serum indicators of markers of endothelial dysfunction in women with gestational endotheliopathy as a result of taking magnesium: vascular endothelial growth factor (p < 0.00001), endoglin (p < 0.00001) compared to patients who did not receive magnesium, and there was also normalization of the of 25(OH)D level in blood serum compared to the control group (p = 0.33). Conclusions. Additional Mg supplementation during pregnancy may reduce the likelihood of perinatal pathology in high-risk patients and help normalize serum markers of endothelial dysfunction in women with high risk of preeclampsia.

Aim. To study the association of nucleotide polymorphisms in platelet receptor and cytochrome P450 genes with the development of resistance to antiplatelet drugs in CHD patients.Material and Methods. The study included 243 patients diagnosed with CHD after coronary artery bypass surgery (CABG), including 140 patients in the acetylsalicylic acid (ASA) treatment group and 103 patients in the dual antiplatelet therapy (DAT) group. All patients were tested for platelet aggregation using an optical aggregometer with inducers: 5 mM ADP and 1 mM arachidonic acid (AA). DNA samples were analyzed by allele-specific PCR for the presence of polymorphisms rs2046934, rs1126643, rs5918, rs6065, rs4244285 in the platelet receptor and cytochrome P450 genes.Results. No statistically significant differences were found during comparison of the prevalence of the studied polymorphisms in the platelet receptor and cytochrome P450 genes between the groups of aspirin-sensitive and aspirin-resistant patients, as well as between the groups of clopidogrelsensitive and clopidogrel-resistant patients. No association between carriage of the minor and major alleles of the polymorphisms studied and the development of antiplatelet drug resistance was found. In the group of patients on ASA therapy, carriers of the C allele of the T1565C (rs5918) ITGB3 polymorphism had a higher rate of AA-induced platelet aggregation compared to carriers of the T allele (18,49±25,92 vs 10,43±17,34, р=0,004).Conclusion. Polymorphisms of P2RY12 (rs2046934), ITGA2 (rs1126643), ITGB3 (rs5918), GP1BA (rs6065), CYP2C19*2 (rs4244285) genes are not associated with antiplatelet drug resistance in both patients on ASC therapy and on DAT. The presence of minor alleles of the rs2046934, rs1126643, rs6065, rs4244285 polymorphisms are not associated with increased platelet aggregation activity before CABG.However, in the group of patients on ASA therapy C-allele carriers of the rs5918 polymorphism of the ITGB3 gene had a higher rate of AA-induced platelet aggregation compared to T-allele carriers.

The article is devoted to modern approaches to the selection of optimal dosage forms of acetylsalicylic acid (ASA), which ensure high bioavailability of ASA drugs. The relevance of improving the tactics of ASA use for both primary and secondary prevention of cardiovascular diseases is discussed. Changes in the role of ASA in the prevention of cardiovascular disease complications are discussed, including as part of combined antithrombotic therapy, including ASA and either P2Y12 inhibitor or low-dose rivaroxaban. Evidence is presented that has led to doubts about the sufficient bioavailability of the enteric form of ASA, as well as the predictability of the response to therapy. A separate part of the article is devoted to the safety of different forms of ASA, in particular - the effect on the mucosa of the small intestine. The results of clinical studies evaluating the effect of ASA intake in enteric-soluble and buffered forms on the small intestinal mucosa and the risk of bleeding are presented. In addition, the problem of decreased effectiveness of ASA intake in overweight or obese individuals is considered. The article provides information on ongoing randomized trials to assess the effectiveness of increasing the frequency of ASA intake, as well as the effectiveness of chronopharmacological approaches to optimize the use of ASA. The analysis performed leads it to conclude that the buffer form can now be considered the preferred acetylsalicylic acid (ASA) dosage form, which, on the one hand, exerts a less pronounced effect on the gastric and small intestinal mucosa, and on the other hand, ensures high bioavailability, as well as minimal variability of treatment response.

Aim: to evaluate the effectiveness of using low molecular weight heparin (LMWH) and low-dose acetylsalicylic acid (ASA) in preventing recurrence of early and late fetal growth retardation (FGR) in patients with antiphospholipid syndrome (APS) and/or genetic thrombophilia.Materials and Methods. A prospective randomized controlled study was conducted by examining 32 patients aged 23 to 43 years with a history of early and late II and III FGR as well as thrombophilia. Prevention protocol using LMWH and ASA was carried out from the pregravid period or early pregnancy. The control group included 35 women with uncomplicated pregnancy. Antiphospholipid antibodies (APA) were measured according to the Sydney antiphospholipid syndrome (APS) criteria by using enzyme immunoassay (ELISA): cardiolipin, β2-glycoprotein 1 and additionally antibodies to annexin V, prothrombin, etc. (IgG/IgM isotypes); lupus anticoagulant – by a three-stage method with Russell's viper venom; antithrombin III and protein C levels – by chromogenic method; prothrombin gene polymorphisms G20210A as well as factor V Leiden polymorphism – by chain reaction; homocysteine – by ELISA.Results. It was found that prevention protocol was effective in 78.1 % cases. FGR re-developed in 7 (21.9 %) pregnant women: in 2 (6.3 %) at 20 and 22 weeks, in 3 (9.4 %) at 30–32 weeks, in 2 (6.3 %) after 34 weeks of pregnancy. All these patients were found to have APA exceeding 40 U/ml with low dynamics of decline, 3 (9.4 %) were older than 35 years, 2 (6.3 %) had chronic kidney pathology and 1 (3.1 %) had a hypertension in the anamnesis.Conclusion. The use of LMWH and low-dose ASA starting from the pre-pregnancy period and early pregnancy as a part of complex therapy allows to effectively prevent re-development of FGR in patients with thrombophilia. In case of high APA titers, the use of LMWH and low-dose ASA may be ineffective, and alternative treatment methods in addition to anticoagulant therapy should be used to improve obstetric results.

Polycythemia vera is not only a clonal disease that causes hematopoietic stem cells, but also a pathology that often leads to thrombotic complications. Thrombosis can have different localization and is clinically manifested by stroke, myocardial infarction, deep vein thrombosis of the lower extremities, pulmonary embolism, thrombosis of the veins of internal organs and other conditions. One of the most formidable thrombotic complications is acute cerebrovascular accident. The heterogeneity of the possible causes of acute cerebrovascular accident requires a careful approach to differential diagnosis for timely diagnosis and individual, pathogenetically grounded selection of means of long-term antithrombotic therapy. The presented clinical case of the development of cerebrovascular accident in a patient with polycythemia vera demonstrates the importance of an informal approach to diagnosis, as well as interdisciplinary interaction for finding the true cause of the development of acute cerebrovascular accident and the appointment of pathogenetically based treatment, aimed, among other things, at the prevention of repeated episodes of acute cerebrovascular accident and others. thrombotic complications.

Expert Council: Drapkina O. M., Vavilova T. V., Karpov Yu. A., Kobalava Zh. D., Lomakin N. V., Martynov A. I., Roitman E. V., Sychev D. A.Scientific communities: the Russian Society for the Prevention of Non-Communicable Diseases (ROPNIZ), the Russian Scientific Medical Society of Therapists (RNMOT), the Russian Antithrombotic Forum (RAF), the National Association for Thrombosis and Hemostasis (NATH).

Nonsteroidal anti-inflammatory drugs, including acetylsalicylic acid, can have a dose-dependent nephrotoxic effect. The study of the pharmacokinetics of acetylsalicylic acid products will contribute to timely detection and correction of side effects caused by this medicinal product.The aim of the study was to evaluate potential nephrotoxic effects following a single oral administration of 75 mg of acetylsalicylic acid, based on the analysis of the pharmacokinetic parameters.Materials and methods: the study involved 24 healthy volunteers who received 75 mg of acetylsalicylic acid (tablets) once orally. The measurement of the active metabolite of acetylsalicylic acid—salicylic acid—in blood plasma was performed by HPLC/MS using an Agilent 1200 liquid chromatography system coupled to an Agilent 6140 tandem mass spectrometer. Agilent Eclipse XDB-C18 column (4.6 mm×150 mm; 5.0 μm) was used for chromatographic separation. The test procedure used in the study was validated. The results obtained were used to calculate the pharmacokinetic parameters: Cmax (maximum concentration), Tmax (time to maximum concentration), T1/2 (half-life of the drug), AUC0-t (area under the pharmacokinetic curve from 0 to the last time point of the curve), AUC0-∞ (total area under the pharmacokinetic curve from 0 to ∞), MRT (mean residence time of the drug in the blood), Kel (elimination rate constant), Cl/F (total clearance), Vd/F (apparent volume of distribution). The Statistics (22.0.0.0) software was used for statistical processing of the results.Results: T1/2 of salicylic acid in blood plasma was determined to be 1.6 ± 0.5 h, Cmax was 4523.0 ± 725.0 ng/mL, and Tmax was 0.98 ± 0.4 h. AUC0–t was equal to 16183.0 ± 3823.0 ng×h/m, Vd/F was 12.0 ± 3.1 L/kg, and MRT was 2.9 ± 0.6 h.Conclusions: the analysis of the pharmacokinetic parameters demonstrated a high absorption rate, intensive distribution, and moderate elimination rate of salicylic acid (the main metabolite of acetylsalicylic acid), indicating a low risk of nephrotoxic effects associated with the studied dose of the drug.

Secondary prevention of cardiovascular disease with aspirin is a very important issue. Аcetylsalicylic acid ensures the prevention of premature death, inhibition of progression and the achievement of partial regression of coronary atherosclerosis, prevention of clinical complications and exacerbations of the disease, reduction of the number of cases and the duration of hospitalization. The most promising direction of modern cardiology is considered to be the prevention of cardiovascular diseases (CVD) and their complications (CVD). This is due to two factors: an increase in the life expectancy of the world’s population as a whole and the persistent leadership of coronary heart disease and brain stroke as the leading causes of death, and disability. The pathogenetic aspects of the administration of acetylsalicylic acid are discussed. The most common dosage form of low-dose (ld) preparations of acetylsalicylic acid (ASA) for preventive use is an intestinal-soluble tablet — 80.6% in the structure of ldASK preparations. Low-dose ASK preparations are mainly presented (84.4%) in the form of monopreparations containing only ASA as the active substance, most often at a dose of 100 mg. However, the side effects of aspirin limit drug intake. This is also due to the high frequency of comorbid diseases such as bronchial asthma and stomach ulcer. The article discusses the issue of prescribing acetylsalicylic acid and the possibility of treating patients with concomitant bronchial asthma, gastric ulcer and obesity. The prevalence of gastroduodenal lesions was significantly lower with intestinal-coated ASA than with buffered acetylsalicylic acid. It was demonstrated that endoscopic lesions of the gastroduodenal mucosa were significantly less likely when using intestinal-coated ASA (100 mg / day) than when using conventional аcetylsalicylic acid, and the assessment of the lesion when using intestinalcoated ASA was similar to the assessment of placebo without аcetylsalicylic acid. In addition, the issue of the possibility of including аcetylsalicylic acid in the treatment regimen for COVID 19 is being discussed.

Aim. Comparative analysis of inhospital outcomes after open thrombectomy versus conservative in patients with acute lower limb artery thrombosis and coronavirus disease 2019 (COVID-19).Material and methods. In this retrospective, comparative study for the period from April 1, 2020 to December 1, 2021, 167 patients with acute lower limb artery thrombosis and COVID-19 were included. Depending on the treatment strategy, two following groups were formed: group 1 — open thrombectomy (n=136) + drug treatment (anticoagulant (unfractionated heparin) and antiplatelet (acetylsalicylic acid 125 mg 1 time per day) therapy; group 2 — only drug therapy (n=31). This group consisted of patients who refused surgical revascularization. In all cases, a psychiatrist examined for personality disorders that did not allow a critical assessment of their condition and the consequences of refusing surgical treatment. At admission to the hospital, all patients received prophylactic-dose unfractionated heparin (5000 IU 3 times/day). In the development of acute arterial thrombosis, 80 IU/kg (maximum 5000 IU) of unfractionated heparin was administered intravenously, followed by transfer to intravenous infusion at an initial rate of 18 IU/kg per hour with the partial thromboplastin time monitoring. Analgesic and antiplatelet therapy (acetylsalicylic acid 125 mg 1 time/day) was also prescribed.Results. Myocardial infarctions, ischemic strokes were not recorded. There were no significant intergroup differences in mortality rates (group 1: n=52, 38,2%; group 2: n=7, 22,6%; p=0,09; odds ratio (OR)=2,12; 95% confidence interval (CI): 0,85-5,27), limb amputation (group 1: n=63, 46,3%; group 2: n=9, 29,0%; p=0,07; OR=2,11; 95% CI: 0,9-4,91). However, there was a trend towards a decrease in the frequency of these events in the conservative therapy group. After open thrombectomy, retrombosis developed in 50,7% (n=69) of cases, whilethrombosis after retrombectomy followed by amputation — in 46,3% (n=63). There were no hemorrhagic complications in both groups.Conclusion. Open thrombectomy with concomitant medical therapy and single conservative therapy without surgical revascularization in the present study showed comparable rates of death and lower limb amputations in patients with COVID-19.

The review presents modern data on the preventive effect of antiplatelet and anticoagulant therapy of placenta-associated diseases. The review includes data from foreign and Russian articles published over the past 15 years on the Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, Pubmed databases. In recent years, there have been reports of the effectiveness of low molecular weight heparins in the prevention of placenta-associated complications. M. Rodger et al. In their study (2016), report on the effect of low molecular weight heparins on the development of placenta-associated complications. Patients whose previous pregnancy was complicated by preeclampsia or fetal growth restriction were randomized into 2 groups. The first group of pregnant women began to receive injections of low molecular weight heparins at an early stage of pregnancy (before 12 weeks), the second group did not receive low molecular weight heparins. Thus, only 19% of women receiving low molecular weight heparin therapy and 43% of women not receiving it developed placenta-associated complications, which may indicate the effectiveness of low molecular weight heparins. This data shows the urgency of the problem of placenta-associated complications, and the development of effective methods of early prevention of these diseases can improve the outcomes of the pregnancy.

A high prevalence of thrombotic disorders, insufficient effectiveness or safety of antithrombotic therapy is an urgent problem of modern healthcare. The main means of preventing thrombosis is acetylsalicylic acid. Despite its long history, aspirin attracts researchers in the fields of medicinal chemistry, biology, and medicine. The development of new antiplatelet agents, including chemical modification of the acetylsalicylic acid molecule, remains relevant. Modification of the acetylsalicylic acid molecule using amino acids and obtaining their salt forms makes it possible to maintain antiplatelet or antithrombotic properties, as well as to impart additional pharmacodynamic effects. In modern science, a lot of attention is paid to the sulfur-containing amino acid taurine. An analysis of modern scientific literature revealed the protective effect of taurine in diabetes mellitus and cardiovascular diseases, liver dysfunction, gastrointestinal tract, and kidney diseases.The aim of the article is to study synthesis of new compounds, determination of their physical characteristics and assessment of their antiplatelet and antithrombotic activities in vitro and in vivo.Materials and methods. To confirm the structure of the synthesized new derivatives of hydroxybenzoic acids with a taurine fragment by the acelation method, thin layer chromatography and NMR spectra were used. In vitro studies were carried out on the model of ADP-induced platelet aggregation according to the Born G. methods modified by V.A. Gabbasov. In vivo, the studies were carried out on the model of arterial thrombosis induced by the application of iron chloride in the following groups of animals: intact, with experimental diabetes mellitus and three-year-olds; the rate of bleeding from the tail vein was also evaluated.Results. New compounds – derivatives of ortho-, meta- and para-hydroxybenzoic acids with a taurine residue – were synthesized. A procedure for the preparation of N-hydroxybenzoyl taurine compounds and their salt forms have been described; their spectral characteristics and melting points have been determined. The synthesized compounds are superior to acetylsalicylic acid in solubility and are not inferior to it in antiplatelet and antithrombotic activities. The results of the in vitro antiplatelet activity assessment in a wide concentration range from 10-4M to 10-8M, are presented. It has been revealed that the dipotassium salt of N-(2-hydroxybenzoyl)taurine exhibits a less antiplatelet activity than the dipotassium salt of N-(3-hydroxybenzoyl)taurine. The most pronounced antiplatelet activity is exhibited by the compound N-(4-hydroxybenzoyl)taurine. In in vivo experiments on the model of arterial thrombosis in 3-year-olds or animals with experimental diabetes mellitus, carotid artery thrombosis occurred faster than in young or intact animals. A single preliminary oral administration of the test compounds prolonged the time of the thrombus formation, which makes it possible to conclude that they have an antithrombotic effect. In this study, the dipotassium salt of N-(3-hydroxybenzoyl)taurine exhibits a more pronounced activity than that of acetylsalicylic acid.Conclusion. Against the background of the modeled pathologies, the studied drugs showed the expected antithrombotic activity, in terms of the severity not inferior to that found in acetylsalicylic acid.

The review is devoted to the analysis of the significance of acetylsalicylic acid (ASA) in the primary and secondary prevention of various manifestations of atherothrombosis. The results of the ARRIVE, ASPREE and ASCEND studies are considered, based on which the evidence base for the use of reduced low-dose ASA (75-100 mg) for primary prevention of cardiovascular diseases (CVD), including patients with diabetes mellitus is formed. Nevertheless, the question of the significance of ASA in primary prevention of CVDs has not been finally resolved, because the results of the latest TIPS-3 study, published in 2020, showed that the combination of enteric-coated ASA with a polypill consisting of a statin and three hypotensive drugs, compared with placebo, reduces the frequency of cardiovascular episodes (CVEs) in individuals without CVDs but with average cardiovascular risk. ASA is an immutable component of dual antiplatelet therapy (DAPT) in patients with acute coronary syndromes (ACS), in patients with coronary heart disease, subjected to planned stenting. Recently, evidence has been obtained about the impact of bleeding on prognostic outcomes, so there is a clear trend to reduce the duration of aspirin therapy in patients with atrial fibrillation and ACS or undergoing planned stenting. A new trend is enhancement of ASA therapy with a second antithrombotic drug in patients with stable manifestations of atherothrombosis with high risk of thrombotic complications. Thus, modern recommendations suggest to enhance ASA therapy with a vascular dose of rivaroxaban (2.5 mg 2 p/day) or a P2Y12-receptor platelet inhibitor. ASA appears to be a classic antiaggregant and an essential partner for new antithrombotic drugs.

The aim of this review is to analyze and summarize the existing evidence regarding the possibilities of using acetylsalicylic acid (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) to reduce cancer risk. Conclusions. Chronic inflammation facilitates the onset and progress of tumour growth. Anti-cancer properties of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs are mediated via cyclooxygenase COX-dependent mechanisms, as well as other tumorigenic pathways. Current systematic review addresses potential role of ASA and other NSAIDs in reduction of cancer risk for the following localizations: head and neck, lungs, gastrointestinal tract, breast, ovaries, prostate, and skin. The role of ASA in primary prevention of colorectal cancer in specific populations is presented in 2016 U. S. Preventive Services Task Force guidelines. Studies indicate heterogeneous protective potential of ASA against different cancer types, depending on studied population, duration of intake and dose. Influence of non-aspirin NSAIDs on cancer morbidity and mortality is more controversial.

The article is devoted to the development of technology for obtaining a drug based on aspirin and paracetamol in the form of capsules. Marketing analysis has shown the relevance of the development of medicinal preparations in the form of capsules in Kazakhstan. The main physical, chemical and technological properties of the substance samples were studied. The quality indicators of the initial raw material and the finished product are determined. Technological calculations were performed.

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils.Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

Cardiovascular diseases are the main drivers of the morbidity and mortality in Russian Federation. We briefly discussed the poor adherence of the patients and outlined the solutions of this problem.

Cardiovascular disease (CVD) and oncological diseases are the leading causes of death in the world. The widespread use of cardiovascular drugs makes it important to study their potential antitumor and carcinogenic effects. The article provides information on the most relevant clinical and experimental studies, which have obtained data on possible antitumor or carcinogenic effects of drugs of basic classes used in cardiology. Current information on the use of acetylsalicylic acid to prevent colorectal cancer is discussed, as well as possible antitumor effects of clopidogrel. The results of studies demonstrating the effect of statins on the risk of cancer development in various localizations are presented. The controversial data on the influence of ACE inhibitors and sartans on the risk of lung cancer and other localizations are discussed. The results of research into beta-blockers as adjuvant therapy for breast cancer are analyzed. The results of studies in which data on possible carcinogenic effects of calcium channel blockers and diuretics were obtained are presented. For each discussed class of drugs, presumed mechanisms of antitumor or carcinogenic action are indicated. The need to develop and introduce drugs to reduce cardiovascular and cancer morbidity into clinical practice by influencing the general pathophysiological mechanisms of CVD and cancer is emphasized. Systemic chronic persistent inflammation is a pathogenetic link between aging, atherosclerosis and carcinogenesis. The results of the CANTOS study opened up new perspectives in the treatment of CANTOS and oncological diseases, and provided a powerful incentive for planning and conducting further studies.

Introduction.The article discusses the search for new and highly effective drugs for the prevention and treatment of cerebrovascular disease. Theaimwas to examine the effect of the acyl hydrazone tropane derivative on individual platelet aggregation (PA) sensitivity in in vitro studies. Results. We present the results of a pilot study on the effect of a new acyl hydrazone tropane derivative acyl hydrazone (2,3,4-trimethoxy-N'-(8-methyl-8-azabicyclo [3.2.1.] octane-3-ylidene) benzohydrazide hydrochloride on PA properties in vitro in healthy volunteers and in patients with chronic cerebrovascular disease. Conclusion. The studied compound has a pronounced ability to suppress PA when administered intravenously in vivo in two concentrations, equivalent to doses of 10 and 100 mg/kg, and its effect is superior to the comparator acetylsalicylic acid, which is used in clinical practice as an antiplatelet drug.

Aim. To compare the kinetics of dissolution (in vitro) and some pharmacodynamic and pharmacokinetic parameters of branded generic preparations of acetylsalicylic acid (ASA) in buffered form in cardioprotective doses [ASA 75 mg+Mg(OH)2 15.2 mg], which differ in the composition of excipients, with a reference drug.Material and methods. Patients with cardiovascular diseases who had indications for ASA monotherapy (n=75) were included in a one-center open postregistration comparative non-randomized study. Patients were divided into 3 groups for treatment with one of the three studied drugs: Cardiomagnyl® (comparison drug; group 1; n=25), Trombital® (group 2; n=25) and Fazostabil® (group 3; n=25). A study of the kinetics of dissolution of the studied drugs in vitro under conditions of pH 1.2 has been performed. Also, platelet aggregation in response to arachidonic acid, the concentration of salicylic acid and the level of serum thromboxane B2 were studied in the compared groups.Results. The average release profile of ASA by the 30th minute from Cardiomagnyl® was higher than for Trombital® and Fazostabil® (95.7%, 84.8%, 76.5% respectively). The similarity factor (f2) of ASA release for Trombital® was 39.3, and for Fazostabil® - 34.2. An index of f2

Aim. Description of risk factors, pathogenesis and treatment strategies of gastrointestinal bleeding (GIB) in the course of antithrombotic therapy in patients with coronary heart disease (CHD).Key points. Risk factors of GIB during antithrombotic therapy in CHD patients include: GIB, gastric and/or duodenal ulcer in the history, reflux esophagitis, presence of H. pylori, inflammatory bowel disease, diverticula, haemorrhoids, angiodysplasia, gastrointestinal neoplasia, age above 65 years, concomitant treatment with non-steroidal anti-inflammatory drugs (NSAIDs), glomerular filtration rate

Cardiovascular disease (CVD) is a major cause of death among patients with diabetes. Antiplatelet therapy is an important part of the treatment and prevention of CVD and acetylsalicylic acid (ASA) is the main medication. This review describes modern approaches to the primary prevention of cardiovascular events in patients with diabetes. Until now, no concerted strategy on this issue has been developed by the global medical communities. The approaches used in the guidelines were heterogeneous and did not cover most of the risk factors, which were often associated with the underlying disease. The risk assessment for CVD with a view to developing risk factor stratification is often difficult due to the variety of manifestations and complications of the disease, as well as the specificity of factors used as independent predictors of atherosclerotic vascular disease for the diabetes population. Only cardiovascular risk analysis in an individual patient can make it possible to choose the best method for prevention. Therefore, the most important objective is to introduce the adopted CVD risk stratification criteria for patients with diabetes into clinical practice, which will enhance the preventive treatment and personalize the therapeutic approaches.The adopted standardized cardiovascular risk analysis system for patients with diabetes, for now, has been implemented in the 2019 European clinical guidelines.The consensus regarding use of ASA adopted by the European Society of Cardiology (ESC) in collaboration with the European Association for the Study of Diabetes (EASD) in 2019 has been based on meta-analyses with a high degree of evidence. They advise to use low-dose ASA in patients with diabetes, if they are at «high» and «very high» risk of CVD and have no obvious contraindications.It allowed clinicians to use low-dose ASA (in combination with proton pump inhibitors) as one of the most important methods for primary prevention. Such modern approaches will surely improve the cardiovascular morbidity and mortality rates in the diabetes population.

Acetylsalicylic acid (aspirin) is one the most widespread drugs in the world. It is used for secondary prevention of atherothrombotic events in patients with cardiovascular disease. Accordingly, the problem of the effectiveness of aspirin treatment is among the crucial issues of cardiology. The issue of personalization of antiplatelet therapy remains relevant, since there is no convincing evidence in favor of using aspirin for primary prevention in the general population. In this review, recent data on aspirin resistance are considered. Potential mechanisms of non-responsiveness to aspirin, the role of genetic factors, standardization of tests and diagnostic criteria for aspirin resistance, and the treatment options are discussed. The data on the clinical and prognostic value of 11-dehydrothromboxane B2 as a promising marker of thromboxane-dependent platelet activation are analyzed.

Introduction. Digital colorimetry is one of the available and simple methods that can be used for the rapid detection of low-quality drugs. The main limitation of the method is its lack of selectivity. To increase the selectivity, the use of molecular sensors is proposed. Molecular sensors are substances that change color during physicochemical interaction with the analyte. Digital colorimetric analysis using a set of sensors allows one to obtain a large amount of information about the sample, however, such a significant amount of data is rather difficult to interpret and use for rapid assessment of the composition of the drug. In addition, the use of a large set of sensors significantly increases the level of information noise. To reduce the influence of the noise component, as well as to reduce the dimensionality of the data, it is advisable to use chemometric algorithms, in particular, the method of principal components (principal component analysis, PCA). It is shown that the using of PCA will make it possible to replace 24 values of the luminosity of color channels with 2-3 numerical values of the main components without loss of analytical information.Aim. Aim of our investigation is the development of a new approach to identifying non-steroidal anti-inflammatory drugs using multisensory digital colorimetry by the principal component method.Materials and methods. The analysis was performed in 96-well transparent polypropylene plates with flat bottom (Thermo Fischer Scientific, USA, № 430341). 100 μl of the correspond-ing sensor and 100 μl of alcohol solutions of non-steroidal anti-inflammatory substance sub-stances were consistently added to the wells of the plate. Sensor solutions were added to a separate row of wells for comparison without adding substance solutions (intact wells). After adding solutions of the substance, the plate was sealed with a film, shaken on a PST-100HL plate shaker (BioSan, Latvia) for 5 minutes and left for 20 minutes to complete the reaction. To obtain raster images an Epson Perfection 1670 office flatbed scanner (CCD matrix) with a removable cover was used. The difference in the lightness of the color channels between the analyte well and the intact well was used as an analytical signal. The obtained digital images of the cells were processed in the ImageJ program using the RGB 24 bit color model (8 bits per channel).Results and discussion. It is shown that the use of chemometric algorithms for processing the results of multisensor colorimetric analysis allows to use the entire data array in obtaining an-alytical information, and not just the lightness values of individual channels of some sensors. The method of principal components allows you to simultaneously get rid of the noise com-ponent of the colorimetric signal and highlight the most sensitive sensors for this sample. The adequacy of the proposed combined approach is confirmed by the identification of active sub-stances in 5 drugs of the group of non-steroidal anti-inflammatory drugs.Conclusion. The approach proposed in this work can be successfully applied as an express and available way to assess the authenticity of medications of the group of non-steroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drug is one of the most commonly prescribed drugs for the treatment of inflammatory and pain syndromes in the clinical practice of doctors of various specialties. The popularity of this pharmacological group is increasing due to over-the-counter dispensing condition, but at the same time, the significance of issues of likelihood, prevention and treatment of severe adverse drug reactions during intake that is controlled and uncontrolled by medical personnel is increasing. This review is devoted to the issue of non-steroidal anti-inflammatory drug-induced damage to the gastrointestinal tract and to the current possibilities to prevent and manage such damage. The drugs that can increase the production of prostaglandins and mucus in the digestive tract and have a general anti-inflammatory effect raise significant hopes. Rebamipide draws particular attention due to numerous pleiotropic effects, including stimulation of secretion of newly formed prostaglandins and glycoproteins in the mucous membranes, inhibition of synthesis of oxidative stress products, inflammatory cytokines and chemokines by intestinal epithelial cells. The authors considered the effectiveness of prophylactic use of rebamipide in comparison with other strategies for the use of drugs to prevent the development of stomach ulcers, duodenal ulcers and distal small bowel ulcers. They described the mechanisms of prophylactic action and its debatable aspects for proton pump inhibitors, H2-histamine receptor blockers, misoprostol. The clinical efficacy of rebamipide is illustrated by a clinical example. The absence of effects on cytochrome P450 enzyme activity, which minimizes the risks of drug interactions and changes in bioavailability, biotransformation and excretion of the drug itself during its course use is an additional advantage of rebamipide.

Aim. Comparative assessment of the economic results of rivaroxaban/acetylsalicylic acid (ASA) combination and ASA monotherapy use in patients with coronary artery disease (CAD) and/or peripheral artery disease (PAD). Material and methods. Based on the results of a large international multicenter, placebo-controlled, randomized clinical trial COMPASS, a model that evaluated the clinical outcomes of rivaroxaban/ASA combination and ASA monotherapy was formed. The economic results using cost and cost-effectiveness analyses, and budget impact analysis for two years were also calculated. The analysis took into account both direct medical costs (expenses for treatment, hospitalization due to complications, rehabilitation) financed under the compulsory health insurance, as well as indirect costs (loss of GDP due to disability or death). The calculation was made by accounting 100,000 patients with CAD and/or PAD.Results. Modeling of clinical outcomes per 100,000 patients based on COMPASS results showed a decrease of stroke prevalence by 649 cases, myocardial infarction — 301 cases, amputations — 478 cases, cardiovascular mortality — 476 cases when using rivaroxaban/ASA combination compared with ASA monotherapy. The cost-effectiveness analysis showed that rivaroxaban/ASA combination has greater clinical efficacy and lower costs in comparison with ASA monotherapy. Budget impact analysis showed that the switching of 100,000 patients with CAD and/or PAD from ASA monotherapy to rivaroxaban/ASA combination leads to budget savings of 1,026 million rubles in two years. This is due to a decrease in the incidence of cardiovascular events.Conclusion. It was found that the use of a rivaroxaban/ASA combination in comparison with ASA monotherapy in patients with CAD and/or PAD can both decrease a number of complications and lead to cost savings, despite the initially higher cost pharmacotherapy.

To date, a sufficient volume of clinical studies has been accumulated that have demonstrated a reduced antiplatelet effect of enteric-coated (EC) lowdose acetylsalicylic acid (ASA). Delayed and incomplete absorption from the intestinal alkaline medium, which significantly reduces the bioavailability of drug, is considered the main reason for laboratory aspirin resistance (pseudoresistance) to EC ASA. This phenomenon is of particular importance for patients with acute coronary syndrome, when a quick effect is required, as well as for patients with diabetes and obesity due to additional causes of increased platelet activity, on the one hand, and reduced bioavailability of ASA, on the other. Given the issue of efficacy, the dubious gastroprotective effect and the more pronounced damaging effect on the mucous membrane of small intestine, the use of EC ASA should be avoided, especially in patients with a multifactorial risk of insufficient response to therapy. A good alternative is buffered ASA, which quickly dissolves and is partially absorbed directly in the stomach, having antiplatelet activity comparable to simple ASA and a similar aspirin resistance, is associated with a lower risk of aspirin-induced enteropathy in comparison with ES ASA. In addition, according to a number of small studies and retrospective analyzes, buffered ASA is less likely to cause damage to gastric mucosa compared to EC ASA.

Aim. To study the production of reactive oxygen species (ROS) by platelets in patients with coronary artery disease (CAD) before and after coronary artery bypass grafting (CABG), depending on their sensitivity to acetylsalicylic acid (ASA) as a part of ASA monotherapy and dual antiplatelet therapy (DAPT) (ASA+clopidogrel).Material and methods. The study included 104 patients with CAD (ASA monotherapy, 64 patients; DAPT, 40 patients). From day 1 after CABG, they took 100 mg a day of enteric-coated ASA. In the DAPT group, clopidogrel was prescribed for 2-3 days after CABG. All measurements were performed before surgery, on the 1st day and days 8-10 after surgery. Control group consisted of 36 healthy donors. Resistance to ASA was determined at a level of optical platelet aggregation with arachidonic acid >20% at least at one observation point. The spontaneous and ADP-induced chemiluminescence (CL) of platelets with luminol and lucigenin was assessed according to the following parameters: time to maximum intensity (Tmax), maximum intensity (Imax), area (S) under the CL curve, and the ratio of ADP-induced CL S to spontaneous CL S.Results. Throughout the study, 71 patients with CAD were sensitive to ASA (sASA) (ASA monotherapy, 46 patients; DAPT, 25 patients), three patients — resistant (rASA) (ASA monotherapy, 1; DAPT, 2). Sensitivity of other 30 patients (ASA monotherapy, 17; DAPT, 13) changed in different follow-up periods. Compared to the control group, sASA patients had increased values of platelet CL parameters throughout the study, while in the rASA group (ASA monotherapy), Tmax was higher before CABG, and in the rASA group (ASA therapy+clopidogrel), Imax and S were higher on the first day after CABG, while Imax — on days 8-10 after CABG. Compared to sASA, the values of S and Imax before CABG, Imax after CABG, as well as Imax and S on the days 8-10 after CABG in rASA (ASA monotherapy) were significantly lower, while in rASA (ASA therapy+clopidogrel), only the Tmax values were lower on the 8-10 days after CABG.Conclusion. In patients with CAD, depending on the sensitivity to ASA and antiplatelet therapy after CABG, the metabolic activity of platelets in terms of ROS production differs. In sASA patients, ROS synthesis is higher than in healthy individuals, while, in rASA patients (ASA monotherapy), platelets produce ROS levels lower than in sASA. CABG surgery and the addition of clopidogrel to ASA therapy leads to increased ROS production in rASA patients in the postoperative period.

Aim. To study the association of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene with resistance to acetylsalicylic acid (ASA) in patients with coronary artery disease after coronary artery bypass grafting (CABG).Material and methods. The study included 90 patients aged 61,5±6,9 years (70 men and 20 women) with II-IV functional class (FC) angina pectoris, according to the Canadian Cardiovascular Society grading. The atherosclerotic nature of coronary artery disease is confirmed by coronary angiography. Patients stopped taking antiplatelet agents before CABG for at least 5 days. The aggregation study was carried out with an optical aggregometer using ADP inducers (5 pM) and arachidonic acid (1 µМ) before CABG, on 1-3 and 8-10 days after surgical treatment.DNA samples were examined for the presence of T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) polymorphisms in the P-selectin gene using realtime PCR with allele-specific primers.Results. When comparing aPTT, fibrinogen level, platelet aggregation activity with ADP inducers (5 µМ) and arachidonic acid (1 µМ), no differences were found among groups of patients with homozygous and heterozygous variants of the studied polymorphisms genotypes, both before and on 1-3, 8 -10 days after CABG. Regarding presence of ASA resistance, patient groups with homozygous variants of genotypes (T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133)) did not statistically differ in prevailing or rare alleles from the corresponding groups with heterozygous genotypes. In the first 10 days of the postoperative period, thrombotic events (4,4%) were observed in 4 patients in the study group: acute myocardial infarction, acute cerebrovascular accident. Regarding frequency of adverse events in the first 10 days after CABG, between groups of patients with homozygous variants of the studied genotypes (T715P (rs6136), M62I (rs2228315), S290N (rs6131), V640L (rs6133) in prevailing allele and groups with heterozygous variants of the corresponding genotypes there were also no statistically significant differences.Conclusion. Rs6133, rs6163, rs2228315, rs6131 polymorphisms in the platelet P-selectin gene are not associated with ASA resistance and are not associated with increased platelet aggregation activity in patients with coronary artery disease. The rare T, C, G, A alleles of the studied polymorphisms do not lead to an increase in the risks of adverse events in the first 10 days after CABG.

Background — venous thromboembolic complications (VTC) are potential life-threatening complications following knee arthroplasty (KA). An optimal thromboprophylaxis strategy should reduce the risk of developing VTC without increasing the risk of hemorrhagic complications. The purpose of the study is to evaluate the effect of the drugs (acetylsalicylic acid, dabigatran etexilate and rivaroxaban) for the pharmacological thromboprophylaxis and the features of the surgical procedure (use of the tourniquet and drainage) on hemorrhagic complications in early periods after knee arthroplasty. Materials and Methods. 335 patients (65 men and 270 women), without additional risk factors for the development of thromboembolic complications, were included into the study. Those patients were admitted for planned primary / revision knee arthroplasty and corresponded to inclusion / non-inclusion criteria. Patients were randomized into three clinical groups, depending on the drug used thromboprophylaxis. During the inpatient treatment period, all patients recorded the development of symptomatic VTCs and the development of hemorrhagic complications. According to the clinical indications, the number of knee joint punctures was taken into account: patella balloting, restricted flexion and a smooth joint contour. Results. Symptomatic VTCs were not observed during the study period. The volume of intraoperative blood loss did not depend on the drugs used for thromboprophylaxis, and was determined only by the surgical technique (ρs= -0.615, p = 0.0001). The use of the tourniquet during the procedure significantly reduced intraoperative blood loss (p = 0.023). No relation between surgical technique and anemia on the 5th day (ρs = 0.11, p = 0.05), as well as between surgical technique and total blood loss (ρs = 0.12, p = 0.01) was established; weak reliable correlation between the use of the tourniquet and hidden blood loss (ρs = -0.22, p = 0.01) was reported. A negative average significant correlation was observed (ρs = -0.42, p = 0.01) for the volume of total blood loss and hemoglobin level on the 5th day after the surgery. The number of postoperative punctures was comparable in the study groups. Conclusion. Sample of present size is not sufficient to make conclusions about the equal efficacy of using acetylsalicylic acid, dabigatran and rivaroxaban for thromboprophylaxis after knee arthroplasty in patients without additional risk factors for thrombosis. Data on the significant correlation of the surgical technique with the volume of intraoperative and latent blood loss, as well as total blood loss and hemoglobin level on the 5th day after the operation allow to suggest a possible effect of the drug for thromboprophylaxis on blood loss stargin from 2nd day after the procedure.

An analytical article discusses the design and results of the recent COMPASS study. Particular attention is paid to the details of comparison of the efficacy and safety of rivaroxaban combined with acetylsalicylic acid and the efficacy and safety of drugs containing acetylsalicylic acid only in patients with stable coronary artery disease. In addition to a significant reduction in the risk of the sum of traditionally recognizable events (myocardial infarction, stroke, cardiovascular mortality), among the arguments in favour of fairly widespread prolonged use of the antiplatelet agent combined with anticoagulant is an attractive effect of the debated antithrombotic strategy on the overall mortality of patients, an acceptable ratio of efficacy and hemorrhagic safety, first of all the absence of the increased risk of fatal bleeding and the risk of intracranial bleeding. The article describes approaches to the selection of patients with coronary artery disease for the participation in the long-term treatment with rivaroxaban combined with acetylsalicylic acid. Alternative possibilities for enhancement of the secondary prophylactic effects of acetylsalicylic acid are mentioned, the arguments supporting the preference of the approach discussed in the article are presented.

Aim. To study the association of V640L (rs6133) polymorphism in the P-selectin gene with acetylsalicylic acid (ASA) resistance in patients with coronary heart disease after coronary bypass surgery (CABG).Material and methods. The study included 104 patients aged 36-78 years (mean age 61.6±6.9 years) with stable angina pectoris: 61 (58.7%) patients had functional class II (according to Canadian Cardiovascular Society), 41 (39.4%) – class III and 2 (1.9%) – class IV. Atherosclerotic lesions of the coronary arteries were confirmed by coronary angiography. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients received 100 mg of ASA in enteric form, 61 patients received alone ASA therapy, 43 patients – combined antiplatelet therapy: ASA+clopidogrel (75 mg/day). The aggregation study was performed with an optical aggregometer, using 5 μM adenosinediphosphate (ADP) and 1 mM arachidonic acid inductors before CABG, on 1-3 day and on 8-10 day after surgical treatment. DNA samples were examined for the V640L (rs6133) polymorphism in the P-selectin gene by real-time polymerase chain reaction (PCR) using the allele-specific primers.Results. The frequency of the homozygous GG genotype of the rs6133 polymorphism was 84.6%; heterozygous GT genotype – 15.4%. The amplitude of aggregation with ADP before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotes of allele G vs carriers of the allele T were: 47.9±19.3%, 44.5±17.8%, 30.1±13.2% vs 47.9±17.1%, 46.3±16.5%, 39.6±22.0%, respectively (p=0.497, 0.441 and 0.687, respectively). The amplitude of aggregation with arachidonic acid before CABG, on 1-3 day and on 8-10 day after CABG for carriers of homozygotesof allele G vs carriers of the allele T, were: 47.9±23.2%, 24.5±21.7%, 12.3±16.3% vs 54.3±17.8%, 29.7±23.7%, 11±10.9%, respectively (p=0.416, 0.825 and 0.872, respectively). In the first 10 days of the postoperative period, 6 thrombotic events (5.7%) were observed in the study group: 2 strokes and 4 perioperative myocardial infarctions. Five events occurred in the group of patients with the GG genotype, 1 event in the group of patients with the GT genotype.Conclusion. V640L (rs6133) polymorphism in the P-selectin gene is not associated with ASA resistance in patients with coronary artery disease after CABG. The T allele of the rs6133 polymorphism is not associated with increased platelet aggregation activity after CABG and does not increase the risk of adverse events in the first 10 days after CABG.

The review analyzes data on the detection rate of and the abilities to predict and prevent non-cardioembolic strokes in non-valvular atrial fibrillation. According to accumulated facts, vitamin K antagonists in non-valvular atrial fibrillation are noted to be inferior to antiplatelet drugs in efficiency in preventing non-cardioembolic (atherothrombotic in particular) strokes, and the widespread use of oral anticoagulants in combination with antiplatelet drugs does not generally reduce the incidence of poor outcomes, markedly increasing the risk of serious bleeding. Nevertheless, it is conceivable that this combination antithrombotic therapy may be useful for certain categories of patients at the highest risk for atherothrombotic stroke and at relatively low risk for hemorrhagic complications. Cohorts of patients, to whom such an approach should be reasonable considered to be applied, have not yet been identified.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective medications in modern pharmacotherapy. At the same time, it has been established that NSAIDs can cause cardiovascular diseases. Glucosamine sulfate (GS) is used in the therapy of osteoarthritis and, according to experimental data; it can exert an antithrombotic effect. This paper evaluates the antithrombotic effects of GS and a number of NSAIDs (such as, acetylsalicylic acid (ASA), dexketoprofen, diclofenac, and meloxicam) through chemoreactome analysis. It has been found that the antithrombotic effects of GS can be on average only 1.5—3 times weaker than those of the NSAIDs studied. The findings may suggest that GS can enhance the antithrombotic effect of ASA, in particular in the presence of cardiovascular disease in patients with osteoarthritis.

Five dosage forms from various manufacturers containing acetyl salicylic acid was investigated with the DSC method. It was found that the amount of acetylsalicylic acid in these preparations is equal to 80-85 wt.%, which corresponds to the regulatory framework of the SP XIII.

It was developed combined dosage form - tablets, each containing 0,25 g of acetylsalicylic acid and 0,1 g of cycvalon that meet the requirements of the State Pharmacopeia XII and State Pharmacopeia XIII. Addition of cycvalon allows to prepare tablets at a low pressure, which will reduce labor, energy costs of manufacture of tablets and to increase the service life of the press tool.

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r = 0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r = -0.75) and S under the curve induced CL (r = -0.70) on the 8-10th day were detected between platelets and neutrophils.Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

Aim. To assess the prevalence, structure, and features of aspirin-induced gastroduodenal lesions in patients with chronic coronary artery disease (CAD) and outline therapeutic options.Material and methods. The study included 340 patients with chronic CAD who received long-term low-dose acetylsalicylic acid (ASA) therapy. The diagnosis of chronic CAD was verified using a complex examination with selective coronary angiography (SCA). Further, esophagogastroduodenoscopy was performed in patients with chronic CAD to diagnose aspirin-induced gastroduodenal lesions. We also assessed their prevalence and structure. An endogenous prostaglandin-inducer rebamipide (300 mg daily) in combination with a proton pump inhibitor (PPI) pantoprazole were used to treat aspirin-induced gastroduodenal lesions. The comparison group consisted of patients with chronic CAD who received only pantoprazole. To clarify the pathogenesis of aspirin-induced gastroduodenal lesions before and after treatment, the levels of following serum pro-inflammatory cytokines were determined: interleukin-6 (IL-6), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNF-α). The control group consisted ofpatients with chronic CAD and without signs of gastrointestinal lesions. Statistical processing was carried out using Statistica 10.0 software package.Results. Aspirin-induced gastroduodenal lesions were recorded in 15% of patients. Results of esophagogastroduodenoscopy revealed that gastric erosions of body and antrum prevailed among aspirin-induced lesions. The level of pro-inflammatory cytokines in these patients was significantly higher than in patients of control group. Therapy with PPI resulted in a positive endoscopic response in 19 of 25 patients and a slight decrease in cytokines. Combination of PPI with rebamipide led to mucosal reconstruction in all subjects and a statistically significant decrease in levels of serum pro-inflammatory cytokines. Conclusion. The current study showed aspects of development and possible therapeutic options in aspirin-induced gastrointestinal lesions in patients with chronic CAD.

Introduction: Acetylsalicylic acid (aspirin, ASA) belongs to nonsteroidal anti-inflammatory drugs group (NSAIDs), characterized by analgesic, antipyretic, anti-inflammatory properties. ASA blocks production of prostaglandins and thromboxanes due to non-competitive irreversible inactivation of cyclooxygenase 1 enzyme (COX1). Nowadays, ASA is most commonly used to inhibit platelet function and to reduce the risk of thrombotic events. The aim of the study: The purpose of this narrative systemic review was to analyse and summarize available data on necessity of acetylsalicylic acid cessation before oral surgery. Material and method: Standard criteria were used to review the literature data. The search of articles in the PubMed and Google Scholar databases was carried out using the following key words: acetylsalicylic acid, oral health, oral surgery. Description of knowledge: According to some medical practitioners dosing acetylsalicylic acid (ASA) before tooth extraction should be stopped because of fear of bleeding complications. However, the cessation of aspirin may predispose patients to thromboembolic events. Most of the data indicates more benefits from continuation aspirin taking than treatment discontinuation. Summary: According to actual knowledge and conducted researches there is no need to stop dosing aspirin before oral surgery. The benefits of using aspirin are greater than the risk of bleeding.

The article reviews the literature on classical and atypical Reye’s syndrome, explores the circumstances that contribute to its occurrence, provides criteria for diagnosing with an illustration in the form of an authentic case of Reye-like disease in a child of 3 years old. Reye’s syndrome is a disease manifested by acute encephalopathy in combination with fatty degeneration of the internal organs, mainly the liver. This condition was first described in 1963 by an Australian pathologist who identified 21 cases of the disease in children with influenza A who were taking acetylsalicylic acid, 17 children died. In the future, the circle of infections that preceded the development of Reye’s syndrome-acute respiratory infections, chickenpox, entero- and rotavirus infections, in rare cases, hepatitis A and HIV, bacterial infections: mycoplasma, chlamydia, whooping cough, shigella, salmonella. Drugs that can cause the development of this syndrome: tetracycline, zidovudine, diclofenac sodium, mefenamic acid, paracetamol, amiodarone, warfarin, phenothiazine derivatives, histaminolytics (dimedrol), valproic acid. Along with drugs, insecticides, herbicides, hepatotoxic fungi can be used as triggers of the syndrome. There is an age dependence of the development of this syndrome. The pathogenesis of classic Reye’s syndrome is associated with generalized damage to the mitochondria primarily in the brain, as well as in the liver, kidneys, muscles, myocardium and pancreas, with the disturbance of oxidation of fatty acids in them and the formation of fat degeneration of varying degrees. In addition to the classic Reye’s syndrome, atypical Reye’s syndrome or Reye-like disease is isolated, occurs in children under 5 with congenital disturbance of oxidation of fatty acids. We observed in our clinic the case of Reye-like disease in a girl of three years with infection and taking antipyretics. In the discussion section, the features of the given case are noted, the question of the appropriateness (in view of the generality of the clinic and the mechanisms of development) of dividing the syndrome into classical and atypical is discussed. A new name for both conditions is proposed — Reye’s disease in honor of the discoverer, highlighting its two forms with an early and late onset. Given the morphological changes in this syndrome — steatosis of internal organs — authors seem to be appropriate measures aimed at treating secondary mitochondrial insufficiency and fatty dystrophy.

The CVD death rates remain high now. The concurrent course of coronary artery disease (CAD) and diabetes mellitus (DM) has an unfavourable prognosis, requires specific therapy and the use of measures to prevent severe complications. DM sometimes hinders the timely diagnosis of CAD, which in this case is characterized by an atypical course and has no florid symptoms. This often causes serious pathological complications or death. The atherothrombosis forms the basis of pathogenesis of severe conditions. Atherothrombosis is not only a generalized, but also a constantly progressive disease, for which reason it is necessary to carry out both primary and secondary prevention. According to the existing guidelines of European Society of Cardiology and Society of Cardiology of Russian Federation, acetylsalicylic acid (ASA) is recommended at small doses as the first-line drug for the prevention of vascular events in patients with CAD. This article discusses the experience of using ASA according to the conducted studies and in practical medicine by the clinical example of a female patient.