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Background. Polymorphic variants of the genes encoding these isoenzymes and carrier proteins involved in the pharmacokinetics of direct oral anticoagulants (DOAC) may alter their function and, therefore, hypothetically may increase the risk of bleeding associated with the use of DOAC. Aims to study the possible relationship between the presence of polymorphic variants of ABCB1 (rs2032582, rs1045642, rs1128503), CYP3A5 (rs776746) and CYP3A4 (rs35599367) genes on the residual equilibrium concentration (Cmin,ss /D) of apixaban, CYP3A isoenzyme activity and bleeding development in patients with AF and CKD C3C4 stages. Methods. The study included 142 patients with AF combined with chronic CKD stages C3 and C4, receiving apixaban therapy, aged 58 to 99 years (median age 84 years). Pharmacogenetic, pharmacokinetic testing and assessment of CYP3A isoenzyme group activity were performed. Results. Plasma concentration of apixaban depended on the stage of CKD: a higher level of Cmin,ss /D was observed in patients with CKD stage C4 compared to patients with CKD stage C3a and with CKD stage C3b. When studying the effect of rs1045642 (C3435T) polymorphism of ABCB1 gene on apixaban pharmacokinetics, it was found that carriers of homozygous TT genotype had lower median apixaban concentration in blood compared to carriers of CC and TC genotypes (p = 0.027 and 0.034 respectively). For rs2032582 polymorphism of ABCB1 gene, we recorded that patients with GG genotype had higher Cmin,ss /D level of apixaban compared to GT genotype carriers (p = 0.037). CYP3A metabolic activity was statistically significantly lower (p = 0.036) in the group with a history of bleeding compared with that in patients in the group without a history of bleeding (0.8 (0.5; 1.3) and 1.2 (0.7; 2.1); p = 0.036). CYP3A metabolic activity did not differ between patients with different CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphism genotypes. For the rs1045642 polymorphic variant, there were fewer carriers of the heterozygous TC genotype (16 (45.7%) patients) among patients with bleeding during the follow-up period compared to patients with no bleeding (43 (53.1%) patients; p = 0.024). Conclusions. The results of the study indicate the presence of an association between genome-wide changes (polymorphic variants of the ABCB1 (rs1045642) and CYP3A5 (rs776746) gene and the presence of apixaban-associated bleeding in patients with AF and CKD stages 34. Mechanisms of such an association require further study.

The problem of differential diagnosis of pleural diseases involves a large number of pathological conditions causing its damage, which physicians are not aware about. Drug-induced (DI) lesion occupies a special place in the structure of pleural diseases, both due to the relatively low prevalence and due to insufficient awareness of doctors about the presence of such adverse reactions in drugs. At the same time, thanks to modern information about the morphology, physiology and pathophysiology of the pleura and pleural cavities, the diagnosis and treatment of pleural diseases are becoming more and more effective. The article presents the data of modern literature and electronic databases of The Drug-Induced Respiratory Disease Website about DI lesions of the pleura. This review provides information about the main types of DI lesions of the pleura and the scope of drugs that cause these reactions. Ultimately, doctors awareness of drug-induced pleural diseases can ensure timely diagnosis of these conditions, correct therapy, and ultimately improve the quality of medical care.

Diarrhea is the most common adverse reaction of anticancer drugs, as well as radiation therapy of the pelvic organs or abdominal cavity: the incidence of diarrhea of different seveity reaches 80% during chemotherapy and / or radiation therapy; one third of these patients develop severe diarrhea (3rd or 4th degree). Most often, drug-induced diarrhea occurs during chemotherapy, using 5-fluorouracil or irinotecan, taking new anticancer drugs from the classes of checkpoint inhibitors, monoclonal antibodies, tyrosine kinase inhibitors. The most common mechanisms underlying the development of drug-induced diarrhea are damage to the intestinal mucosa, impaired absorption of proteins, carbohydrates, fats, inflammation, a perverse immune response, microflora imbalance, and others. Algorithms for the management of patients with severe diarrhea include suspension (grade 1-2, 3) or complete cessation (grade 4, grade 3) of the use of an antineoplastic agent an inducer, prescribing drugs that reduce intestinal motility (loperamide) while excluding the infectious nature of diarrhea, intravenous methylprednisolone (for example, diarrhea caused by monoclinal antibodies in the absence of suspicion of potential bowel perforation). In cases where drug-induced diarrhea lasts more than 48 hours, or a patient reports symptoms of dehydration, or a fever occurs, urgent hospitalization is necessary. The objective of this review is to analyze scientific literature data on the prevalence, pathophysiological mechanisms and risk factors for the development of diarrhea associated with the intake of anticancer drugs, as well as its prevention and treatment.

Upper respiratory tract infections (URTI) are a large group of infectious diseases (mainly viral and bacterial), affecting the mucous of the nasal cavity, paranasal sinuses, pharynx and larynx. URTI are very common in inpatient and outpatient clinical practice. In this article, we present a clinical case of Patient N., 20 years old, consulted with upper respiratory tract damage caused by Chlamydia pneumoniae. The patient admitted to clinical diagnostic center on 07.07.2021 with complaints of pain in the left maxillary sinus with irradiation to the left temporal region, difficulty in nasal breathing, pain in the pharynx, aggravated by swallowing, and increased body temperature (37,5 °C). The patient was consulted by an interdisciplinary team (ENT doctor and clinical pharmacologist). After carrying out physical, instrumental and laboratory tests the diagnose Chlamydia pneumoniae - associated URTI was established and, the patient was prescribed doxycycline at a dose of 100 mg 2 two times a day on the 1st day following by 100 once a day for the next 6 days with a positive effect. The doxycycline was choisen because of a more favorable safety and efficacy profile compared to fluoroquinolones and some other antibacterial agents. After 7 days of treatment, the patient recovered completely. Among all doxycycline drugs available on the market of the Russian Federation, Doxycycline Express (JSC Pharmstandard-Leksredstva) stands out due to its high quality, bioequivalence to the original drug and comfortable regime of use due to the dosage form (dispersible tablets), that increases the patient’s compliance and allows it to be used by some special categories of patients (elderly and senile patients, patients with dysphagia, etc.

Stroke is an acute disturbance of the blood supply to the brain, characterized by the sudden onset of focal neurological symptoms, which persists for more than 24 hours or leads to the death of the patient in a shorter period of time due to cerebrovascular pathology. In the world and in Russia, stroke remains one of the leading causes of death and disability. At the same time, ischemic stroke (IS) is more common – about 80% of cases. Many classes of drugs, such as oral contraceptives, nonsteroidal anti-inflammatory drugs, and various psychoactive substances, can contribute to the development of drug-induced IS (DI IS). Data upon the frequency of DI IS is limited. In part, this reflects the problem of identifying and confirming the causal relationship between drug prescription and the development of IS. DI IS risk factors include: abuse of caffeine and alcohol, older age, smoking, drug addiction, high doses of drugs containing provoking agents, the simultaneous use of several drugs, the presence of comorbid diseases. Adverse drug reactions develop due to the following pathophysiological mechanisms: cerebral embolism, vasoconstriction of cerebral arteries, vasculitis of the central nervous system, orthostatic hypotension. The management of a patient with a DI IS does not differ significantly from the management of a patient with IS of a different etiology and includes thrombolysis or mechanical thromboextraction (in the absence of contraindications), as well as rational methods of secondary prevention. It is necessary to completely cancel or reduce the dose of the drug, the use of which led to the development of a stroke. DI IS prevention measures include the choice of drugs with the lowest risk of its occurrence and the use of modern scales for assessing the risk of this phenomenon.

Daytime somnolence may be a symptom of different somatic, neurological and psychiatric diseases and develop due to abuse and/or discontinuation of various medications. Drug- induced hypersomnia (DIH) is defined as hypersomnolence caused by the intake of multiple drugs. DIH is one of the most frequently reported effects and/or side effects of drugs. DIH prevalence varies widely and can be as high as 75% in patients receiving specific medications. DIH risk factors include elderly and senile age, impaired drug metabolism, serum drug concentration, method and frequency of drug administration, single and daily doses of drugs, etc., as in many other drug- induced diseases and syndromes. DIH can occur both due to sedative agents administration and withdrawal of psychostimulants and other activating psychotropic medications. Most often, the development of DIH is associated with the use of levodopa-carbidopa, antipsychotics, antidepressants. The pathogenesis of DIH is complex and multifactorial and is associated with the mechanism of action of individual drugs and the presence of concomitant diseases. The article discusses the risk assessment of DIH development due to various medications, diagnosis and management tactics of patients with DIH.

Objective. Data analysis on modern therapy strategies of chronic heart failure (CHF) and the possibilities of adjuvant therapy with phosphocreatine. Methods. Analysis and systematization of the positions of the year 2020 Russian Ministry of Health clinical guidelines on CHF and modern local and international literature data.Results. Currently, for the treatment of CHF, a wide range of drugs are used that can improve the prognosis and reduce mortality in patients, including β-blockers, blockers of the renin-angiotensin-aldosterone system, diuretics, aldosterone antagonists and neprilisin inhibitors. At the same time, based on the peculiarities of the pathogenesis of CHF and the characteristics of the myocardial energy metabolism in heart failure conditions, a promising direction is the use of additional (adjuvant) drugs in this category of patients. Here, a special place is occupied by phosphocreatine, which is essential in maintaining the energy balance of cardiomyocytes and has been widely studied in a large number of studies that have confirmed its ability not only to increase exercise tolerance in patients with CHF, but also to improve heart systolic function and prognosis, improving patient survival. Conclusion. Based on the reviewed body of evidence, a rational approach in the management of patients with CHF is to add adjuvant phosphocreatine therapy to the standard treatment strategy according to the current clinical guidelines, which provides an additional improvement in prognosis and a decrease in mortality rates in patients.

Optimizing diuretic therapy in patients with chronic heart failure is a complicated problem with many unresolved questions. Diuretics take an important place in the treatment of heart failure, which are used in almost 80% of cases. Currently, there are not enough clinical studies, which comparative effectiveness of loop diuretics, as well as studies aimed at personalizing diuretic therapy. Torasemide has several advantages over other loop diuretics; high bioavailability, longer half-life and duration of action provide predictable diuresis. The presence of favorable neurohormonal effects, consisting in a decrease of sympathetic activity and inhibition of the renin-angiotensin-aldosterone system, leads to the fact that hypokalemia rarely occurs. In addition, torasemide slows development of myocardial fibrosis and fosters reverse ventricular remodelling. The use of personalization methods is one of the ways to increase the efficiency and safety of pharmacotherapy with diuretics. The polymorphism of genes encoding systems of biotransformation and transporters of drug is an important factor that determines the individual characteristics of a patient. Pharmacogenetics of torasemide may be of significant importance for pharmacokinetics and pharmacodynamics, influencing the intensity of the diuretic effect and side effects. The clearance of torasemide after oral administration may vary by 47% due to genetic characteristics: the participation of the OATP1B1 polymorphism is approximately 15.5%, the CYP2C9 polymorphism is 20%, and the OAT1 and OAT4 polymorphisms are 10%. Due to the significant differences in the pharmacokinetics of torasemide, further study of the pharmacodynamic characteristics of torasemide in patients with genetic polymorphism is necessary.

Aim. To assess the efficacy and safety of Vamloset (amlodipine/valsartan 5/80, 5/160, 10/160 mg) and Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide 10/160/12.5, 10/160/25 mg) in achieving the target levels of blood pressure (BP) in patients with stage 23 arterial hypertension (AH). The article discusses indicators affecting adherence to antihypertensive therapy (AHT). Material and methods. The VICTORY II Russian study in 8 clinical centers of the Russian Federation included 103 patients over 18 years of age with stage 23 essential AH (who havent been previously treated and have office systolic BP160 mm Hg and/or diastolic BP100 mm Hg or who havent reached the target office blood pressure with mono- or double AHT). The Full Analysis Set (FAS) for efficacy analysis included 99 patients, a FAS population with the restoration of data missed using Last Observation Carried Forward. The SF-36 questionnaire for assessing the quality of life, the effect on erectile function in men, the convenience of current therapy from the point of view of patients were analyzed after 16 weeks of treatment. The Per Protocol (PP) population included 80 patients completing the study without major protocol deviations to assess the primary parameters of efficacy. All patients with stage 2 hypertension were prescribed Vamloset (amlodipine/valsartan 5/80 mg), with stage 3 hypertension amlodipine/valsartan 5/160 mg. Dose titration of Vamloset and Co-Vamloset (LLC Krka-RUS) was carried out every 4 weeks according to the AHT schemes. Results. The studys active phase included 100 patients aged 59.510.9 years (women 59%) with AH duration of 83.48.4 months; 83% of patients received AHT prior inclusion in the study. In the PP population, 16 week- AHT with Vamloset or Co-Vamloset allowed reaching the target BP in 90.0% of patients (95% confidence interval [CI] 81.295.6). Overall clinical efficacy was achieved in 98.8% of patients (95% CI 93.2100.0). All treatment regimens were characterized by high patient compliance. In the total group, 50% of patients rated their AHT as more convenient than they had previously used; of them, in the stage 2 AH group 47.8%, in the stage 3 AH group 53.3%. Metabolic neutrality with regard to at least one indicator was observed in 100% of patients, with regard to 6 indicators in 43.9% [33.9; 54.9]. For all 98 patients included in the analysis, changes in all SF-36 scales, except for physical functioning (p=0.339), were statistically significant (p0.05). The effect of AHT on erectile function was rated as positive in 51.3% of men. Good tolerance data are consistent with the established drug safety profile. Conclusion. In the VICTORY II study, high antihypertensive efficacy and an improvement in a set of indicators of optimal adherence to AHT by Vamloset and Co-Vamloset within 16 weeks were proved in patients with stage 23 AH. Patients high rating for quality improvement in the quality of life, safety of therapy and ease of use ensured optimal compliance of Vamloset and Co-Vamloset therapy throughout the study.

Clinical guidelines have long been one of the working tools of the modern doctor, helping him quickly navigate the most effective proven methods of treatment and prevention of various diseases, and also to adapt these methods to the specific tasks of their patients and to achieve maximum personalization of treatment. Clinical practice guidelines are drawn up by professional non-profit associations and are approved by the Scientific Council of the Ministry of Health of the Russian Federation, while often one recommendation is prepared by two or even three associations. The peculiarity of the recommendations offered to your attention is that not only endocrinologists, but also therapists, cardiologists, gynecologists, gastroenterologists, and experts of many other specialties are involved in the prevention and treatment of obesity. The Multidisciplinary Working Group presents this a project in a multidisciplinary journal to bring together the efforts of several professional associations that associated with the need to pay attention not only to obesity itself but also to comorbid conditions. We are looking forward to constructive criticism and a comprehensive discussion of the problem on the pages of our journal.

In 2021, the world cardiology community celebrates the anniversary of one of the greatest research in clinical medicine – the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) study. The study showed that in patients with atrial fibrillation, the use of apixaban was more effective than the use of warfarin in the prevention of stroke or systemic embolism, was accompanied by a lower frequency of bleeding and was associated with lower mortality from all causes. To date, 77 subanalyses of this ambitious study have been published, a brief overview of which is given in the article. As shown by the post-hoc analysis of the ARISTOTLE study, apixaban was equally effective and safe both in patients without comorbidities and in polymorbid patients. The efficacy and safety of apixaban has been demonstrated in atrial fibrillation and in the presence of comorbidities, including diabetes mellitus, chronic kidney disease, obesity, and coronary heart disease. A number of subanalyses of the ARISTOTLE study are devoted to the prognostic assessment of biomarkers such as cardiac troponins, growth differentiation factor-15, pro-B-type N-terminal natriuretic peptide, D-dimer, asymmetric and symmetric dimethylarginine, interleukin-6, C-reactive protein. Based on the study of biomarkers, new, more informative scales for assessing the risk of stroke, death and bleeding were created: the ABC-stroke scale, the ABC-lethal outcome scale and the ABC-bleeding scale. The data of the corresponding sub-analyzes confirmed the greater efficacy and/or safety of apixaban treatment compared with warfarin, regardless of the level of various biomarkers in blood plasma and the degree of risk of stroke, death and bleeding, assessed using both traditional and new scales.

Aim. Assessment of Vamloset® and Co-Vamloset effects on blood pressure target levels and indicators associated with organ protection: albuminuria; elasticity of arteries and central aortic pressure (CAP); endothelial function; tumor necrosis factor-a, interleukin (IL) IL-6 and IL-10, vascular cell adhesion molecule 1 and vascular endothelial growth factor (VEGF-A). Materials and methods. The Russian multicenter open-label prospective clinical study VICTORY II which was conducted in 8 clinical centers included 103 patients >18 years with grade 2–3 essential arterial hypertension (AH), who were previously untreated – office systolic blood pressure (SBP) ≥160 mm Hg and/or office diastolic blood pressure (DBP) ≥100 mm Hg – or have not reached the target office blood pressure with mono- or dual therapy. The active phase of the study included 100 patients; the per-protocol (PP) population – 80 patients completing the study without major protocol deviations. Patients were not randomized. The target office BP for patients without diabetes were: SBP≤139 mm Hg, DBP≤89 mm Hg; for patients with diabetes: SBP≤139 mm Hg, DBP≤84 mm Hg. All patients with grade 2 hypertension (group 1) were administrated Vamloset® (amlodipine/valsartan, 5/80 mg), with grade 3 hypertension – Vamloset® (amlodipin/valsartan, 5/160 mg). Up-titration of the dose of amlodipine/valsartan to 5/160 mg and 10/160 mg, the administration of Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide) in doses of 10/160/12.5 mg, 10/160/25 mg (LLC «KRKA-RUS») was carried out every 4 weeks according to the prescribed schemes. In the total group, the effect of studied therapy on the level of albumin in the urine was assessed. Before starting treatment and after 16 weeks of treatment, 40 patients in the subgroup with additional examinations underwent daily monitoring of blood pressure, assessment of pulse wave velocity and augmentation index; CAP; levels of tumor necrosis factor-a, IL-6 and IL-10, vascular cell adhesion molecule 1and VEGF-A. Results. The active phase of the study included 100 patients aged 59.5±10.9 years (59% of women) with a duration of AH 83.4±8.4 months. 83% of patients received prior antihypertensive therapy by the time of enrollment in the study. The treatment duration for all patients was 15.9 weeks. After 16 weeks, therapy with Vamloset® and Co-Vamloset provided an optimal decrease in BP: 90% of patients with grade 2–3 AH in the PP population reached the target level of office BP, the mean change in SBP / DBP was -32.2/-16.0 mm Hg. According to the data of daily monitoring of BP in the subgroup with additional examinations, the target levels of average daily SBP/DBP were reached in 52.9/67.6% of patients, respectively. Along with reliable control of blood pressure, additional organ protection with studied antihypertensive drugs after 16 weeks of therapy was shown by assessment data: albuminuria – in 58.8% of patients with an initially elevated level of albuminuria (n=17), a positive effect of the studied therapy on the level of albumin in the urine was determined, augmentation index – improvement in 57.1% of patients in the study group, CAP – improvement in 73% of patients in the study group; positive dynamics of endothelial damage markers (IL-6, IL-10, VEGF-A) was achieved. The data on the good tolerability of AHT corresponded to the previously established safety profile of these drugs. Conclusion. In the VICTORY II clinical study in patients with grade 2–3 hypertension, along with high antihypertensive efficacy, a spectrum of organoprotective effects of Vamloset® and Co-Vamloset on aortic stiffness with improved augmentation index and CAP, markers of endothelial damage (IL-6, IL-10, VEGF-A), the severity of albuminuria was shown.

The novel coronavirus infection (COVID-19) caused by the b-coronavirus SARS-CoV-2, and leads to acute respiratory distress-syndrome, has affected more than nineteen million people worldwide, resulting in 0 7 million deaths as of August 2020 The fact that the virus uses angiotensin-converting enzyme 2 as a receptor for entering the target cell, and the high prevalence of hypertension and other cardiovascular diseases among patients with COVID-19, have caused serious discussions on the management of such patients This consensus of experts from the Russian Medical Society for Arterial Hypertension analyzed the existing data on the relationship between COVID-19 and hypertension, the pathophysiological aspects of the penetration of the virus into target cells and the use of renin-angiotensin-aldosterone system inhibitors in patients with hypertension and COVID-19 Новая коронавирусная инфекция (COVID-19), вызванная b-коронавирусом SARS-CoV-2, которая приводит к развитию острого респираторного дистресс-синдрома, затронула более 19 млн человек во всем мире, что привело к 0,7 млн смертей по состоянию на август 2020 г Установленный факт, что вирус использует ангиотензинпревращающий фермент 2 в качестве рецептора входа в клетку-мишень, и высокая распространенность артериальной гипертонии и других сердечно-сосудистых заболеваний среди пациентов с COVID-19 вызвали серьезные дискуссии по ведению таких пациентов В консенсусе экспертов Российского медицинского общества по артериальной гипертонии проанализированы существующие данные о связи между COVID-19 и артериальной гипертонией, патофизиологические аспекты проникновения вируса в клетки-мишени и применения блокаторов ренин-ангиотензин-альдостероновой системы у пациентов с артериальной гипертонией и COVID-19

The relationship between blood pressure (BP) and cerebral blood flow (CBF) is not fully understood. This study evaluated the impact of a perindopril arginine/indapamide (Pa/I) single-pill combination (SPC) on CBF in middle-aged patients. A total of 22 treatment-naive patients with essential hypertension and at least one hypertension-mediated organ damage and 41 healthy controls were enrolled. At baseline, all participants underwent brain magnetic resonance imaging (MRI); patients with hypertension underwent an additional MRI at end of follow-up. Arterial spin labeling (ASL) was used to calculate CBF in the frontal lobe cortical plate. Patients with hypertension received once-daily Pa/I 5 mg/1.25 mg SPC, which could be increased to Pa/I 10 mg/2.5 mg at 2 weeks if necessary. Patients with hypertension underwent 24-h ambulatory BP monitoring (ABPM) at baseline and end of follow-up. Mean baseline BP values were 146.2/93.1 and 119.1/76.1 mmHg in the hypertension and control groups, respectively. Patients with hypertension had significantly (p

VICTORY II study objective. Evaluation of Vamloset and Co-Vamloset safety and effectiveness in reaching target blood pressure (BP) level in patients with stages 23 arterial hypertension (AH). Materials and methods. Russian multicenter prospective clinical study conducted in 8 clinical centers in6 cities in Russian Federation included 103 patients over 18 years of age with diagnosed essential hypertension of stages 23 (in accordance with 2013 European guidelines) who previously did not receive treatment (with office systolic BP sBP160 mm Hg and/or office diastolic BP dBP100 mmHg) or did not achieve target BP levels after receiving mono- or dual therapy. Office BP target levels comprised 139 mmHg for sBP and 89 mm Hg for dBP for patients without diabetes mellitus (DM), and 139 mm Hg for sBP and 84 mm Hg for dBP for patients with DM. All patients with stage 2 AH (group 1) were prescribed Vamloset (amlodipine/valsartan, 5/80 mg), patients with stage 3 AH Vamloset (amlodipine/valsartan, 5/160 mg). Therapy correction Vamloset (amlodipine/valsartan) in doses 5/160 mg, 10/160 mg and Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide) in doses 10/160/12,5 mg, 10/160/25 mg (КРКА-RUS) was performed every 4 weeks according to provided schemes. At follow-up every 4 weeks the decision on necessity of antihypertensive treatment (AHT) correction were made by medical researcher in accordance with analysis of patients complaints, general condition and physical examination, results of office BP measurement, diary of BP self-control. In 40 patients in subgroup with additional assessment 24-hour BP monitoring, pulse wave velocity measurement, central BP evaluation, augmentation index calculation, and endothelium damage markers determination were performed. Results. Active phase of the study included 100 patients aged 59.510.9 years (59% female) suffering from AH for 83.48.4 months. The patients received treatment with study medication (safety population). The protocol population (sampling Per Protocol) included 80 patients who completed the study without severe protocol violation. At the moment of study entrance 83% of patients received AHT. In all patients treatment duration comprised 15.9 weeks. In Per Protocol population target office BP level was achieved by 90.0% (95% confidence interval 81.295.6%) of the patients. Overall clinical effectiveness (extremely high, very high, high, and sufficient) was achieved in 98.8% [95% confidence interval 93.2100%] of the patients. In group of patients with stage 2 AH target office BP level was achieved by 93.8% of patients, in group with stage 3 AH by 84.4% of patients. Mean BP change in study group was -32.2 mm Hg for SBP and -16.0 mm Hg for DBP. Among patients with stage 2 AH target office BP level was achieved by 93.8% of patients, with mean BP change -30,7 mm Hg for SBP and -15.5 mm Hg for DBP. In patients with stage 3 AH target BP levels were achieved in 84.4% of patients with mean BP change -34,6 mm Hg for SBP and -16.7 mm Hg for DBP. After 16 weeks of treatment in Full Analysis Set population with recovery of missed measures using Last Observation Carried Forward 40.2% of patients reached target BP levels according to BP self-control results. Considering the limitations of results evaluation this practice requires further assessment, standardization, and improvement. According to 24-hour BP monitoring reaults after 16 weeks of treatment 26.5% of patients achieved target BP daily profile (for patients from subgroup with additional assessment in Full Analysis Set population with recovery of missed measures using Last Observation Carried Forward), that indicates additional influence of studied AHT on the prognosis of patients with stages 23 AH. Conclusion. In clinical study VICTORY II Vamloset and Co-Vamloset optimal effectiveness and safety in patients with stage 2 and 3 arterial hypertension were shown.

Heart failure (HF) is a growing public health problem with an estimated prevalence of 38 million patients worldwide. Congestion and formation of edema – are typical symptoms of heart failure. Diuretics are the mainstay of therapy in heart failure and are used to relieve congestion and improve exercise tolerance. Also, the administration of diuretics should be considered to reduce the risk of HF hospitalization. Loop diuretics are used by nearly 80% of all chronic HF patients and remain the drugs of choice. Although diuretics are one of the most prescribed classes of drugs, recommendations for their titration scheme for long-term use have not yet been finalized, nor have there been major prospective randomized controlled studies on the effect of diuretics on morbidity and mortality. A Cochrane meta-analysis has shown that in patients with chronic HF, loop and thiazide diuretics might reduce the risk of death and worsening of HF in comparison to placebo and could lead to improved exercise capacity. Guideline recommends the use lowest possible dose of diuretics due to probable electrolyte disturbances, further neurohormonal activation, accelerated kidney function decline, and symptomatic hypotension. Diuretic resistance is associated with an unfavorable prognosis and an increased risk of readmission. There are significant pharmacokinetic differences between the loop diuretics. Compared with furosemide, torasemide has a high bioavailability irrespective of food intake, and carries a longer half‐life and duration of effect; also, the benefits of torasemide are its additional anti-fibrotic and neurohormonal effects. Optimization of diuretic therapy in patients with HF remains a challenge and requires further research, as well as an individual approach to patients, since there is no convincing evidence base.

Cardiovascular diseases are the leading cause of death both in the world and in the Russian Federation. The most significant contributors to the increase in mortality are arterial hypertension (AH) and ischemic heart disease (IHD). Dihydropyridine calcium channel blockers (CCBs) are the first line of treatment for these conditions. This is noted in the clinical guidelines for the diagnosis and treatment of AH and in the guidelines for the management of patients with chronic coronary syndromes. CCBs are a heterogeneous group of drugs that have both general and individual pharmacokinetic and pharmacodynamic properties. They are used in patients with AH and/or IHD, including those with concomitant diseases (diabetes mellitus, chronic kidney disease, bronchial asthma, chronic obstructive pulmonary disease, peripheral arterial disease). Felodipine is one of the CCBs. It has a combination of clinical effects, allowing the drug to be prescribed as a first-line therapy for AH, IHD and a combination of these diseases. This is noted in the registered indications for its use. This CCB has a sufficient evidence base of clinical trials demonstrating not only good antihypertensive and antianginal potential of the drug, but also the nephroprotection and cerebroprotection properties. The nephroprotective effect of felodipine is associated with a slowdown in the progression of chronic kidney disease, and the cerebroprotective effect is associated with a decrease in the risk of stroke and an improvement in cognitive functioning. The safety profile of felodipine is favorable: peripheral edema develops much less frequently. This is confirmed by the results of comparative studies. Felodipine is recommended for a wide range of patients with AH, IHD and their combination due to such clinical and pharmacological properties.

In patients with arterial hypertension (AH), an extremely important measure of the effectiveness of antihypertensive drugs (AHD) is not only a direct decrease in blood pressure (BP), but also its stable control throughout the 24 hours, preventing excessive morning surge and increased BP variability, which in turn are recognized cardiovascular risk factors. Currently, in the vast majority of hypertensive patients, the main antihypertensive therapy approach is using single-pill combinations (SPC) of AHD. Among the first-line combinations for a wide range of patients with AH and no special clinical conditions is amlodipine/telmisartan SPC. Distinctive features of these drugs, on the one hand, are unique pharmacological properties, consisting in an ultra-long antihypertensive effects, superior to other AHD in their classes; and on the other hand, there is an large body of evidence from numerous clinical trials confirming their high antihypertensive and target-organ protective potential as well as excellent capabilities in cardiovascular risk reduction. To assess the AHD effectiveness extent, several parameters have been proposed, of which the most rational and useful is the smoothness index, calculated using the ambulatory blood pressure monitoring data. Smoothness index describes both the degree of BP reduction and its distribution during the monitoring period. This index inversely associates with the changes in BP variability, and has predictive value in relation to the hypertension-mediated organ damage regression during different antihypertensive regimens. Amlodipine/telmisartan SPC has also been studied in many trials, including comparative ones with other AHD. In these works its direct powerful antihypertensive effect and a pronounced beneficial impact on the smoothness index have been proved, demonstrating stable BP control throughout the 24 hours (especially in the most dangerous morning hours), and also a decrease in BP variability. Therefore, amlodipine/telmisartan SPC can effectively reduce cardiovascular risk and improve prognosis in patients with AH.

VIII Eurasian Congress of Cardiology. Overview of symposiums. New opportunities for reducing cardiovascular risk in the Russian Federation. Systemic Hypertension

The COVID-19 pandemic that has swept the planet has posed many questions for doctors around the world, including the tactics of managing patients with cardiovascular disease, both infected and self-isolated. A symposium held with the support of the Merck company was devoted to this problem: "COVID-19: a patient with cardiovascular pathology at a particular risk".

Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

Stroke remains one of the leading causes of death and disability both worldwide and in Russia. Acute cerebrovascular events have many risk factors, among them the most important is arterial hypertension (AH), which predisposes to the stroke development through the direct effect of increased hydrostatic blood pressure on the brain vascular system, followed by arterial remodeling and an increase in their stiffness. In addition, excessive blood pressure variability, activation of the tissue renin-angiotensin-aldosterone system, as well as target-organ damage - primarily the heart in the form of left ventricular hypertrophy, kidneys in the form of microalbuminuria and decrease in glomerular filtration rates. An additional risk factor for stroke is hyperuricemia, which is included in the current European and Russian guidelines for the management of AH as one of the new risk factors in patients with this disease. The state-of-the-art approach to antihypertensive therapy is the using of antihypertensive single-pill combinations, one of the frontline combinations in the absence of special clinical conditions is a combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker. The reference drugs in both classes due to large body of evidence are ramipril and amlodipine, respectively. These drugs provide a high level of brain protection, not only due to the ultra-long and powerful antihypertensive action, but also through a unique potential in target-organ protection via left ventricular hypertrophy regression, antiatherosclerotic effects and improved endothelial function, renal protection, as well as the ability to decrease uric acid in the blood.

Older age is associated with changes in bone metabolism, a loss in its mineral density and volume, and the development of osteoporosis. The high prevalence of atrial fibrillation and osteoporosis in older age groups causes their frequent combination in this category of patients. It is known that some diseases and/or drugs used to treat them, exacerbating the natural violation of bone metabolism, contribute to the progression of osteoporosis and its complications, which in turn can negatively affect the prognosis and quality of life of the patient. Anticoagulants, widely used in the treatment of thromboembolic complications and in the prevention of stroke, can have an adverse effect on bone metabolism. The purpose of this review was to generalize and systematize the available literature data regarding the features of the influence of various representatives of the anticoagulants group on bone tissue. The article analyzes the effects of unfractionated heparin, low molecular weight heparins, vitamin K antagonists, oral anticoagulants on bone metabolism, bone mineral density, and fractures. This review provides data from articles and reviews published through February 2020, inclusive, accumulated in the English-language database of medical and biological publications “PubMed”. The literature data confirm the negative effect of unfractionated heparin on bone tissue, with a violation of bone metabolism, a decreased bone mineral density and the development of fractures. Compared with unfractionated heparin, low molecular weight heparins appear to be safer, and vitamin K antagonists, having a significant effect on bone metabolism, contribute to a decreased bone mineral density, mainly in people who are on long-term (more than 1 year) therapy. Oral anticoagulants, having the mildest effect on bone metabolism, is associated with a lower (compared to other anticoagulants) risk of decreased bone mineral density and the development of fractures, and are recognized as the safest against bone tissue.

Atrial fibrillation (AF) is a common rhythm disorder, especially in the elderly and senile people, and its incidence is expected to be only increasing. Another urgent problem of modern health care is cognitive impairment (CI) and dementia, which are also highly prevalent. Studies show that AF and CI are closely interrelated: patients with this heart rhythm disturbance are at increased risk for both CI in general and dementia in particular, their cognitive decline progresses faster regardless of whether AF is paroxysmal or permanent. The association between CI and AF is largely due to the commonality of risk factors, the main of which are considered to be elevated blood pressure, atherosclerotic vascular damage, diabetes mellitus, and age. To date, the specific pathogenetic mechanisms of CI development in AF have been described, indicating that both vascular and neurodegenerative changes are implicated in cognitive decline in the presence of cardiac arrhythmias in question. These changes include a history of stroke, the well-known risk factor for the cardioembolic type of which is AF; microembolism and microhemorrhage; predisposition to prothrombotic states; cerebral hypoperfusion and a proinflammatory shift associated with this arrhythmia. In addition, a potential adverse effect on CI can be produced by the use of antagonists of vitamin K, since the latter is an important trophic factor necessary for normal cognitive functioning.

Many classes of medications, such as antipsychotics, anticonvulsants, anticholinergics, and other commonly prescribed drugs, can cause cognitive impairment (CI). The negative effect of drugs on cognitive functions is due to the following pathophysiological mechanisms: a reduction in neuronal excitability, an increase in gamma-aminobutyric acid activity, and decreases in enzyme activity, the number of receptors, cerebral perfusion, as well as brain atrophy; moreover, a number of mechanisms have not been fully studied. An important role in the development of drug-induced CI is played by predisposing (senility or childhood, brain damage, chronic diseases, functional disorders, genetic causes, initial cognitive decline, polypragmasia), and precipitating (acute diseases, infections, metabolic disorders, dehydration, acute urinary retention, malnutrition, environmental influences, etc.) factors. The dose of a drug, the duration of its use is of absolute value. There is a need for the differential diagnosis of CI induced by drugs and CI directly related to the diseases, for which these drugs are prescribed. Drug-induced CI should be suspected if an association is established between a decline of cognitive functions and the start of drug intake. The treatment of this CI involves primarily dose withdrawal or reduction and the use of sustained-release dosage forms, if available. In some cases, cognitive training and/or special drug therapy may be required to correct the CI that has occurred. The measures to prevent drug-induced KI include the choice of the lowest-risk drugs, the use of current side-effect rating scales, in particular an anticholinergic burden scale.

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.Results. Significant (pConclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined.

Arterial hypertension (AH) is one of the most significant modifiable risk factors that increase cardiovascular morbidity and mortality worldwide, including Russia. The complex of structural and functional changes in the heart that occurs during AH consists not only in the formation of left ventricular (LV) myocardial hypertrophy, but also in the myocardial stiffness increasing due to collagen formation and cardiomyocytes apoptosis. These abnormalities are substrate for diastolic function disturbances, electrical myocardial instability and ischemia. The article provides a clinical case of amlodipine/lisinopril single-pill combination (A/L SPC) use in real clinical practice in a patient with stage II grade 2 newly diagnosed AH and its effect on blood pressure and echocardiographic myocardial fibrosis markers, including speckle tracking parameters The high antihypertensive efficacy of A/L SPC, a favorable effect on blood pressure circadian rhythm, as well as pronounced target-organ protective properties, in particular the ability to reduce LV and left atrial stiffness, were demonstrated. So, we conclude that A/L SPC improve the elastic properties of the left heart.

Research results show that poor glycemic control and recurrent episodes of severe hypoglycaemia are associated with a decrease in cognitive function in elderly people with type 2 diabetes mellitus (T2DM). On the other hand, patients with diabetes mellitus associated with cognitive impairment/dementia are most at risk of developing hypoglycaemic conditions. It is obvious that the relationship between hypoglycaemia and dementia is very complex and has a mutually aggravating nature. Studies also show that individuals of older age groups with diabetes and cognitive impairment have a high risk of developing hypoglycaemic conditions, such as unwanted side effects from glucose-lowering therapy. In this case, of particular interest is the question that is being actively studied at the present time, which is concerning the effect of different groups of glucose-lowering antidiabetic drugs on the cognitive status and the rate of cognitive decline in diabetic patients with cognitive impairment. In this review, we attempted to summarise, systematise, and present data available in the literature concerning the effect of hypoglycaemia on the risk of cognitive impairment and dementia in elderly and senile patients with type-2 diabetes, as well as the degree of participation in this process of of various groups of sugar-lowering antidiabetic drugs.

Arterial hypertension (AH) is one of the most common diseases in the elderly. It has been proven that lowering blood pressure (BP) is effective in preventing stroke and cardiovascular complications in patients even at the age of ≥80 years. On the other hand, there is evidence that a significant decrease in BP can be harmful to older people and may lead to a higher risk of overall mortality. Therefore, existing guidelines for the treatment of AH determine specific approaches for managing patients of older age groups, where the target BP levels are determined not only by age and concomitant diseases, but also by the presence of frailty. Moreover, there is a need to monitor the dynamics of frailty indicators (social, functional, cognitive and mental status of the patient), since their deterioration may require changes in the tactics of antihypertensive therapy (dose reduction, drug withdrawal or replacement) and changes in target BP levels. In this regard, in recent years, the possibility/necessity of a planned and controlled process of dose reduction, drug withdrawal or replacement, if this drug can be harmful and/or does not bring benefits (deprescribing), has attracted attention. This article is a review of current literature, which presents the design and main characteristics of randomized clinical trials (RCTs) and systematic reviews on the deprescribing of antihypertensive drugs in elderly patients with AH and frailty. An analysis of these studies showed the benefits of deprescribing of antihypertensive drugs for elderly patients with frailty, which avoids potential harm to their health, improves the quality of life and reduces the economic cost of treatment. Therefore, deprescribing of antihypertensive drugs can be used as an additional tool to achieve the necessary target BP values in patients of an older age group. However, for the development of deprescribing of antihypertensive drugs schemes and its introduction into clinical practice, the results of large specially planned RCTs are needed to study this issue.

Tardive dyskinesia (TD) is a type caused by the use of different medications. The pathogenesis of TD is associated with dopamine receptor blockade, gamma-aminobutyric acid depletion, cholinergic deficiency, oxidative stress, impaired synaptic plasticity, and neurotoxicity. TD most often occurs after taking metoclopramide, antipsychotics, antidepressants, calcium channel blockers, and other drugs. The review considers an adequate assessment of the potential risk of TD when the patient uses prescribed drugs, as well as the monitoring and correction of risk factors for TD, discontinuation or replacement of drugs that potentially cause TD, as well as its treatment.