Rational Pharmacotherapy in Cardiology

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Scientific and practical peer-reviewed journal for cardiologists and internists "Rational Pharmacotherapy in Cardiology" has been coming out since 2005 with the support of the Russian Society of Cardiology and the National Medical Research Center for Therapy and Preventive Medicine. It is All-Russian edition with a periodicity of 6 issues a year. The Journal is recommended for the publication of the results of master’s and doctor’s dissertations according to the List of editions of the State Commission for Academic Degrees and Titles. It is distributed by subscription and for free at special events.

The Editorial Board consists of leading Russian scientists in the field of cardiology, preventive cardiology, internal medicine, clinical pharmacology and preventive pharmacotherapy, including 26 Doctors of Science and 6 Academicians of the Russian Academy of Sciences. The Editorial Board consists of well-known National and International cardiologists.

The Journal mainly contains original study articles, scientific reviews, lectures, analysis of clinical practice. The Journal highlights the problems of early diagnosis, primary and secondary prevention of cardiovascular diseases, associated conditions, effective pharmacotherapy, and current questions of experimental and clinical pharmacology.

All manuscripts are published for free. They are subject to a thorough scientific expertise: double-blind review, plagiarism check, multi-stage editing. Authors are required to submit a statement of disclosure of conflict of interest associated with the publication. Reviewers are experts on the subject of peer-reviewed material. In each issue the best original articles are translated and published in Russian and English languages.

The Journal has website ( in English and Russian where the full texts of published materials for all years are available in open access. The Journal is also available in open access on the website of the Scientific Electronic Library (SEL) and has a high impact factor of the Russian Science Citation Index (RSCI). Full-text electronic versions of all published materials are also available on the website of the Russian Scientific Electronic Library CyberLeninka and international open access website DOAJ. Published materials are presented in the international electronic databases Scopus, Web of Science, EMBASE, Index Copernicus, Ulrich's Periodicals Directory.

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Current issue

Vol 17, No 2 (2021)
View or download the full issue PDF (Russian)


178-185 135

Aim. To study medication adherence in elderly patients with coronary artery disease (CAD) in primary care practice.

Material and methods. The study conducted in out-patient clinic of Moscow city. 293 elderly (≥65 years) patients with established CAD included. The following patient data obtained via electronic medical record system: demography, medical history, modifiable risk factors and prescribed pharmacotherapy. Level of medication adherence measured by Morisky scale (MMAS-8) via telephone survey.

Results. According to Morisky scale high adherence was identified in 146 (49.8%) elderly patients, moderate adherence – in 99 (33.8%) patients, low adherence – in 48 (16.4%) patients. Analysis of specific questions of the scale done in non-adherent patients revealed signs of unintentional non-adherence due to forgetfulness (45.9%) and signs of intentional non-adherence due to patients feeling worse (35.8%) or better (28.4%). By means of dichotomic interpretation of Morisky scale results the population under research was divided into two groups: 147 (50.2%) non-adherent patients and 146 (49.8%) – totally adherent patients. These groups were comparable in terms of sex (female 71.2 vs 68.0%; p>0.05) and age (median 73.5 vs 73.0 years; p>0.05) distribution, and medical history: myocardial infarction (39.0% vs 38.8%), atrial fibrillation (37.0 and 41.5%), chronic heart failure (90.4% vs 91.2%), diabetes (26.7% vs 24.5%). There were fewer smokers in adherent group (0.7% vs 6.5%; p<0.05). As primary antianginal pharmacotherapy adherent and non-adherent patients were equally prescribed beta-blockers (75.3% vs 75.5%; p>0.05). Drugs that improve prognosis were also prescribed comparably: antiplatelets (66.4% vs 61.9%; p>0.05), anticoagulants (36.3% vs 44.9%; p>0.05), statins (82.2% vs 79.6%; p>0.05), renin-angiotensin system inhibitors (89.0 and 87.8%; p>0.05). Adherent patients had lower mean values of lipids: total cholesterol (4.7±1.2 vs 5.2±1.4 mmol/l; p<0.05) and low density cholesterol (2.4±0.9 vs 2.8±1.2 mmol/l; p<0.05). Non-adherent elderly patients made more visits to general practitioner (median 5 vs 3 visits; p<0.05). Share of patients receiving drugs within supplementary pharmaceutical provision program was comparable in both groups (53.7% vs 50.7%; p>0.05).

Conclusion. Half of elderly patients with CAD are non-adherent to treatment in primary care setting. Medical history and structure of pharmacotherapy do not influence level of adherence in this population. Among adherent patients fewer individuals smoke and mean values of lipids are lower. Non-adherent elderly patients cause higher load on general practitioner, supplementary pharmaceutical provision program provided no better adherence in the population under research.

186-192 55

Atrial fibrillation (AF) is the most frequent type of supraventricular arrhythmias. The anticoagulant therapy should be prescribed to prevent thromboembolic events. According to randomized clinical trials, anticoagulants do not always prove their high efficiency in the real clinical practice. It is a complicated issue for any doctor to prescribe the anticoagulant therapy for patients with AF and CKD. 30 % of patients with atrial fibrillation are known to have chronic kidney disease, while 10-15% of patients with chronic kidney disease are diagnosed with atrial fibrillation. Currently, there are scarce studies into the use of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease (in case of Glomerular Filtration Rate (GFR) below 45 ml/min/1.73 m2).

Aim. To determine the dynamics of GFR in patients with AF and CKD (in case of GFR below 45 ml/min/1.73 m2).

Material and Methods. The sub-analysis was carried out to examine a single-centre prospective study into the optimization of the anticoagulant therapy in the outpatient practice. Initially, 133 dabigatran taking patients were enrolled in the study, and 79 patients were included in the final analysis. Endpoints were changes in Glomerular Filtration Rate (CKD-EPI) formulae as of the inclusion date, in 6, 12, 24 and 60 months after the inclusion. Changes in the renal function shall mean a decrease or increase in GFR by ≥5 ml/min.

Results. The average follow-up period for patients was 1785 ± 218 days. A GFR>45 ml/min/1.73 m2 occurred in 116 (87.2%) patients, and a GFR <45 ml/min/1.73 m2 was found in 17 (12.8%) patients. The average HAS-BLED score was 1.8, and CHA2DS2VASc score - 3.8. During the observation period, there were 3 cases of major bleeding and 133 cases of minor bleeding. Both major (р=0.025) and minor (р=0.012) bleeding were statistically significant more frequent in patients with GFR below 45 ml/min. During 5 years of follow-up, 66 (49.6%) patients had an average decrease in GFR of 3.32 ml/min/1.73 m2 per year. Patients with the initially declined GFR (below 45 ml/min) did not demonstrate a significant dynamic of the renal function during the dabigatran therapy. The mortality rate in this group during the observation period was 61.5%.

Conclusion. In 49.6% of patients during 5 years of follow-up, GFR decreased by an average of 3.32 ml/min/1.73 m2 per year, which does not exceed the indicators typical for patients with cardiovascular events and CKD.

193-199 57

Aim. We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.

Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 mcg/kg) intravenously. Primary endpoints: restoration of sinus rhythm (SR) within 24 hours after the start of infusion of the study drug in a total dose of up to 30 pg / kg; registration of SR on an electrocardiogram (ECG) 24 hours after the start of the study drug infusion. Secondary endpoints: restoration of SR after infusion of the study drug at a dose of 10 pg / kg; restoration of SR after infusion of the studied drug in a total dose of up to 20 pg / kg; no recurrence of AFib/AFl after restoration of AFl within 24 hours of observation after the start of the study drug infusion.

Results. Conversion to SR was achieved in 53,6% (391 of 727) after administration of 10 mcg/kg dose, in 73% (531 of 727) after administration of 20 mcg/kg dose and in 91,6% (666 of 727) after administration in dose up to 30 mcg/kg. SR was restored in 89% (402 of 451) of patients in primary center, and in 96% (264 of 276) of patients in other hospitals; 95% confidence interval (CI): (-0,1;-0,03). SR preserved 24 hours after conversion in 98% (650 of 666) successfully converted patients. In primary center SR preserved in 97% (390 of 402) successfully converted patients. In other hospitals - in 98,5% (260 of 264) successfully converted patients. 95 CI: (-0,09;0,06).

Conclusion: In post-registration multicenter trial Refralon demonstrated high effectiveness in conversion of AFib and AFl to SR. In other hospitals Refralon did not demonstrate lower effectiveness than in primary medical center.

200-205 65

Background. Current guidelines describe in detail the approaches to the management of patients with resistant hypertension, however, in real clinical settings the number of non-rational and ineffective combinations of antihypertensive drugs used remains high.

Aim. To analyze the distribution of different combinations of antihypertensive drugs for the treatment of resistant hypertension and to estimate the proportion of non-rational combinations.

Methods. The retrospective analysis includes 117 outpatients with resistant hypertension. Resistant hypertension was defined as blood pressure that remains above goal despite concurrent use of three antihypertensive agents of different classes. Exclusion criteria was secondary hypertension. We defined rational combination as the standard combination (renin-angiotensin system [RAS] blocker + calcium-channel blocker [CCB] + diuretic) plus one of the group of reserve drugs (mineralocorticoid receptors antagonist [MRA], beta-blocker, alpha-blocker, agonist of imidazoline receptors [AIR]). Non-rational were considered combinations in which reserve drugs were used before the appointment of a triple combination of first-line drugs. Moreover, in a subgroup of non-rational therapy, situations were identified where such a combination was justified.

Results. The proportion of rational combinations was 58.9%, reasonably non-rational - 15.5%, unreasonably non-rational - 25.6%. Unreasonably non-rational combinations are distributed as follows: non-appointment of CCB - 12%, non-appointment of RAS-blockers - 8%, non-appointment of diuretics - 6%, use of RAS-blockers for hyperkalemia - 6%, administration of MRA without non-potassium-sparing diuretics - 5%, double blockade of RAS - 3%, other combinations - 7%. In addition to first-line drugs, beta-blockers (93.2%), loop diuretics (22.2%), AIR (21.4) were the most prescribable, while the proportion of MRA is only 15.4% of the entire sample.

Limitation: some patient's characteristics could be missed in case histories and some of the combinations could be falsely recognized as malpractice since the analysis was conducted retrospectively.

Conclusion. The proportion of the non-rational combinations for the treatment of resistant hypertension is high. Among the drugs of the reserve, the frequent use of beta-blockers and moxonidine and the inadequate administration of spironolactone are noteworthy. The problem of treatment strategy choice remains relevant in real clinical practice.

206-211 63

Aim. To study the frequency of administration of direct oral anticoagulant (DOACs) in doses recommended and not recommended by the instructions of the drugs in non-valve atrial fibrillation (AF) patients.

Material and methods. 10663 case histories of patients hospitalized for 5 years (2014-2018) were studied, 1307/10663 (12,3%) case histories of patients with AF were selected. In patients with AF, the risk of stroke and systemic embolism, the risk of bleeding, the anticoagulant therapy (ACT) recommended at the prehospital stage and its adequacy was evaluated.

Results. 1 261/1 307 (96,5%) patients had a non-valve AF. The risk of stroke and systemic embolism was 4,7±1,5 (CHA2DS2-VASс), 97,5% of patients with non-valve AF (1229/1261) needed ACT. Only 665/1229 (54.1%) patients with AF received ACT at the time of hospitalization and 578/1229 (47,0%) of patients did not receive ACT. Before hospitalization 281/665 (42,3%) patients received vitamin K antagonist (warfarin). The international normalized ratio in the target range (2,0-3,0) was in 111/281 (39,5%) patients. 57,7% (384/665) outpatients with AF received NOAC: rivaroxaban - 180/384 (46,9%) patients, dabigatran etexilate - 110/384 (28,6%) patients, apixaban - 94/384 (24,5%) patients. Inappropriate reduced doses of DOAC were revealed in 68/384 (17,7%) patients: apixaban - 23,4%, dabigatran - 16,4% and rivaroxaban - 15,6% (p>0,05).

Conclusion. In real clinical practice 42,3% AF patients used warfarin, only 39,5% of them had INR in target values. DOAC in inappropriate reduced doses used 17,7% patients.

212-220 30

Aim. To study the main relationships of the white coat effect (WCE) levels in patients with arterial hypertension (AH) with bronchial asthma (BA) who treated with AH and BA drugs in routine clinical practice.

Material and Methods. We analyzed the prospective cohort study data of AH patients, some of them had BA without exacerbation. We have formed two groups of patients:1 - control group, patients with AH without BA, the second - with AH + BA. The study consisted of three visits (first visit, 6 months and 12 months visits) and data collection period (30.1±7.6 months of follow-up). The following procedures were performed at the first and 12 month visits: clinical blood pressure (BP) measurements (sitting and standing), 24-hour monitoring ambulatory (ABPM), spirometry, clinical and biochemical blood tests, BA control questionnaires (ACQ) and quality of life (QL) questionnaire (GWBQ), at the second visit clinical BP measurement was performed and, if necessary, the drug dose was corrected.

Results. The study included 125 patients, 28 men, 97 women. The first group of AH patients without BA included 85 people, the second (AH + BA) - 40. In AH patients without BA with ischemic heart disease, arterial revascularization, regular alcohol intake and smoking we identified the association with the lower WCE levels. In AH+BA patients with diabetes mellitus, gastrointestinal diseases, higher education was identified WCE decrease. In AH patients without asthma we found inverse relationships WCE levels with respiratory function parameters, the nighttime BP decrease, heart rate and the difference between standing and sitting BP levels, and correlations with the EchoCG variables (the left ventricular hypertrophy (LVH) indices), with age, AH duration and body mass index (BMI). In patients with AH + BA we found inverse correlations between WCE levels and some EchoCG variables, the difference between standing and sitting BP levels, and correlations with body weight, BMI.

Conclusion. Thereby, in AH patients without BA with ischemic heart disease, revascularization, regular alcohol intake, smoking we identified the association with the lower WCE levels. This patients WCE indices had inverse correlations with height, respiratory function parameters, the BP nighttime decrease, the difference between standing and sitting BP levels and direct relationships with EchoCG variables of LVH, age, AH duration and BMI. In AH + BA patients with diabetes, gastrointestinal diseases, higher education we found relationships with lesser WCE manifestation. WCE levels in this group had inverse correlations with some EchoCG indicators, the standing and sitting BP difference and direct relations with weight and BMI.


221-227 70

Aim. To assess comorbidities in elderly patients with acute coronary syndrome (ACS) and to analyze patient subgroups with different treatment strategies in the Regional Vascular Center (RVC).

Material and methods. The prospective study included 205 patients with confirmed ACS 75 years and older, the mean age was 81±4.9 years, and 68% were women. ST segment elevation myocardial infarction (STEMI) was diagnosed in 46 (22.4 %) patients, non-ST segment elevation myocardial infarction (NSTEMI) was diagnosed in 159 (77,6 %) patients. The Charlson Comorbidity Index (CCI) was calculated in every patient. Early outcomes were defined as those assessed during hospital stay. Late outcomes were assessed at 6 months after the discharge using phone calls and/or clinic visits. All patients provided written informed consent.

Results. Percutaneous coronary intervention (PCI) was performed in 42% of patients. In patients with STEMI and NSTEMI PCI was performed in 73% and 32%, respectively. Mean CCI score was 7.9 points: 7.6 points in men and 8.04 in women. Patients with STEMI had higher CCI score than NSTEMI patients (p<0.01): 8.1 points and 7.1 points, respectively. Patients who underwent PCI had lower CCI score (7.2 points) than patients in non-PCI group (8.2 points; p<0.05). Patients with STEMI in PCI and non-PCI groups had significant difference in CCI score (p<0.05): 7.4 and 8.4 points, respectively. Mean CCI score in patients who died in hospital was 8.5 while discharged patients had 7.6 points (p<0.01). In 6 months 13 patients (6.3%) died, their mean age was 84.9 years, mean CCI was 9 points, PCI was performed in 3 (23%) patients.

Conclusions. Elderly patients with ACS had high comorbidity level assessed by CCI score. Higher CCI score was associated with PCI non-performance in elderly patients. Elderly patients with STEMI had higher CCI score than patients with NSTEMI which was significantly associated with PCI non-performance. Patients who died in hospital or in 6 months after the ACS onset had higher CCI score than other elderly patients with ACS.

228-232 32

Aim. To study the current state of the anticoagulant's prescription in elderly and senile patients with atrial fibrillation in the clinical practice of family medicine center, in the southern regions of the Kyrgyz Republic.

Material and methods. Of the 1974 ambulatory medical observation cards, 470 patients with atrial fibrillation were selected who had indications for prescribing antithrombotic therapy (87 [18.5%] men and 383 [81.5%] women; 212 [45.1%] urban residents and 258 [54.9%] rural residents). The average age was 66.9±10.2 years. The analysis included data from 387 patients who received anticoagulant therapy. The frequency of prescribing antithrombotic therapy has been studied.

Results. There were indications for anticoagulant therapy in 387 patients. Anticoagulants were taken by 167 (43.2%) patients, antiplatelet agents - 196 (50.6%), no therapy - 24 (6.2%). Anticoagulant therapy in 153 patients included warfarin, while only 11.8% had adequate INR control after one year of follow-up. Rivaroxaban was prescribed in 14 (8.4%) patients. 50% of patients had antiplatelet agents instead of anticoagulants, which were mainly prescribed by therapists of rural family medicine centers.

Conclusion. In the southern regions of the republic, an unfavorable situation is observed with the prescription and management of elderly and senile patients on anticoagulant therapy. It is necessary to continue the research across the country in order to obtain a complete and real picture of the problem, and to develop a unified and relevant recommendation.

233-238 80

Aim. To study the results of thrombolytic therapy and accuracy of electrocardiographic assessment of thrombolysis efficiency in inferior myocardial infarction with and without right ventricular lesion.

Material and methods. The118 patients with inferior myocardial infarction were included in this study. They received TLT in the first 12 hours of the disease. The dynamics of ST-segment in 90 minutes from the TLT start and coronary angiography data were analyzed.

Results. Right ventricular myocardial infarction (RVMI) was diagnosed in 49 (41.5%) of 118 patients by echocardiography. Patients with and without RVMI did not differ in age, gender and comorbidities, but patients with RVMI were more likely to have arterial hypotension, atrioventricular block, and atrial fibrillation. All patients with RVMI had occlusion of the right coronary artery (RCA) in the proximal (34.7%) or medial segment (65.3%). Occlusion of the circumflex coronary artery was found in 20 (29.0%) patients without RVMI, and RCA occlusion - in other patients. The infarction-associated artery blood flow equal TIMI 2-3 was found in 17 (34.7%) patients with RVMI and in 46 (66.7%) patients without RVMI (p<0.005). ST-segment decrease by 50% or more in 90 minutes from the TLT was found in 35 (71.4%) patients with RVMI and in 49 (71.0%) patients without RVMI (p>0.05). The false-positive assessment of thrombolysis efficiency was noted in patients with and without RVMI in 21 (42.9%) and 11 (15.9%) cases (p <0.005), respectively. There were no false-positive assessments in patients with RVMI when using ST-segment decrease to the isoline.

Conclusion. TLT should be considered effective in patients with inferior myocardial infarction with the right ventricle lesion, if ST-segment decreases to isoline in 90 minutes from the TLT start.


239-248 30

The similarity of the pathogenesis of atherosclerosis and atherothrombotic complications, regardless of their location, makes the approaches to secondary prevention similar, which include lifestyle modification, pharmacotherapy of hemodynamic disorders, metabolic changes and hemostasis. Secondary prophylaxis in patients with multifocal arterial lesions using antihypertensive, antithrombotic and lipid-lowering therapy provides a more pronounced decrease in the incidence of cardiovascular complications than in lesions of single vascular lesions due to a higher initial risk. However, these treatments do not reduce the risk to the level that is achieved by treating patients with less atherosclerotic lesion. In this regard, it is of interest to use the currently available new methods and regimens of drug therapy in patients with multifocal arterial lesions, which make it possible to more intensively influence the mechanisms of atherosclerosis progression and more effectively prevent the development of its complications.


249-255 32

The article discusses the main methods of evidence in modern medicine. Special attention is paid to randomized controlled trials and observational studies. The advantages of randomized controlled trials over observational studies are considered. A comparison of the informative value of randomized controlled trials and observational studies in assessing the effect of therapeutic interventions is made. Attention is drawn to situations when conducting randomized controlled trials is not possible and when they become the main source of information. It is emphasized that in order to verify the results of randomized controlled trials in real clinical practice, it is necessary to conduct observational studies. The basic principles of conducting observational studies are considered.


256-262 56

The coronavirus pandemic showed not only an increase in levels of excess morbidity and mortality in the acute phase, but also persisting symptoms 4 weeks after the onset of the disease. A review of international studies on the prevalence and diversity of the manifestations of postcoid syndrome is presented. The data on such a manifestation of post-COVID syndrome as postural orthostatic tachycardia syndrome (POTS) are accumulating. Pathogenetic mechanisms, modern diagnostic criteria and research data on the prevalence of this syndrome are presented in the article. The Canadian Cardiovascular Society has proposed medications as a treatment for POTS, including the sinus node If channel inhibitor ivabradine. Data from several studies showing the effectiveness of this drug for POTS, including after suffering COVID-19, are presented in the article. Clinical data on the prevalence of tachycardia among patients admitted to the Sechenov University hospital are presented. About 18% of patients with hypertension and 21% of patients with normal blood pressure had a high heart rate. A clinical example of the use of ivabradine in a patient after a coronavirus infection is presented. Drug interactions and individual tolerance of ivabradine in patients after coronavirus infection are being discussed. The authors put forward the hypothesis about the further prospect of using ivabradine in the treatment of clinical manifestations of postcoid syndrome on the basis of literature data and their own experience.

263-269 37

Perfusion scintigraphy and single-photon emission tomography of the myocardium are promising methods for complex assessment of the state of the left ventricle myocardium in patients with chronic heart failure. These methods of nuclear cardiology can be performed in patients with reduced renal function, as well as the presence of implanted devices such as implantable cardioverters-defibrillators, resynchronizing devices and cardiac modulating therapy, which is their undeniable advantage. The reproducibility of the method is ensured bu fully automated calculation of parameters of myocardial perfusion and contractility. To date, there are no data in the literature on the use of nuclear cardiology methods as an imaging technique in patients with cardiac contractility modulation devises. This paper describes the current possibilities and prospects of nuclear medicine methods in patients with chronic heart failure after implantation of a heart contractility modulator.

270-277 31

Atrial fibrillation is the most common arrhythmia in clinical practice. It is associated with an increased risk of stroke, chronic heart failure, and sudden cardiac death. Our options of restoring and maintaining sinus rhythm have a very limited effect, both in the case of antiarrhythmic and catheter treatment. Catheter ablation has proven to be a more effective approach than antiarrhythmic therapy. The success rate of the procedure reaches 70%. However, radiofrequency ablation is associated with a risk of complications, with 4.5% of patients likely to develop major complications, including tamponade (1.31%), femoral pseudoaneurysm (0.71%), and death (0.15%). Given the generally recognized dominant role of the pulmonary veins in the induction of atrial fibrillation, their electrical isolation has become the recommended tactic of the catheter approach. In the case of patients with paroxysmal form of atrial fibrillation, the success rate of the procedure reaches 87%. Unfortunately, in the case of persistent forms of atrial fibrillation, the effectiveness of the primary procedure decreases to 28% and reaches 51% with repeated interventions. In addition to the anatomically oriented isolation of the pulmonary veins, a number of strategies have been proposed to reach the secondary zones of atrial fibrillation induction. The results of recent studies on the effectiveness of strategies for ablation of rotor regions and their role in the induction and maintenance of AF may lead to the further development of catheter ablation techniques and an individual radiofrequency ablation approach in a particular patient.

278-285 30

This review presents an analysis of recent publications on the principles of diagnosis and management of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The authors emphasize the importance of patient's operability assessment regarding the possibility of performing pulmonary thrombendarterectomy - a radical treatment option due to complete post-thrombotic material removal from the branches of the pulmonary artery. In the case of an inoperable type of CTEPH, such a method of transcatheter treatment as step-by-step balloon angioplasty of the pulmonary artery (BPA) is proposed. The article clearly outlines the principles of selection, patient training and techniques for BPA. The authors demonstrated their own patented method of the peripheral vascular bed visualization in the case of recanalization of chronic occlusions, which increases the safety of this intervention. Particular attention is paid to hybrid approaches using a soluble guanylate cyclase stimulator, riociguate in combination with BPA for high risk CTEPH patients. The review presents the data of the post hoc analysis of the CHEST-1 study and the data of real clinical practice of the use of riociguat in combination with the endovascular method of treatment on the example of the leading expert groups in Europe, who demonstrated in their studies the positive effect of riociguat on the hemodynamic parameters and the frequency of perioperative complications.

286-293 155

Prescribing drugs not in accordance with the official instructions for medical use (off-label) has medical and legal aspects. From a medical point of view, such an appointment can be dictated by clinical urgency, when there is no alternative therapy, and on the other hand, doctors often prescribe off-label drugs unknowingly, and also when there is another drug with registered indications. The article analyzes the regulations governing such appointments. The article describes possible inconsistencies between clinical guidelines and standards of medical care in this matter, the role of the medical commission, the impact on the quality and safety of medical care, as well as the types of legal liability of a medical worker that may arise when a drug is prescribed not according to instructions.

294-302 33

Anticoagulant therapy of patients with atrial fibrillation is an integral part of their treatment strategy. The high risk of developing a cardioembolic stroke and the high comorbidity of this group of patients necessitates a comprehensive approach to treatment, taking into account all available risk factors. Atrial fibrillation is often asymptomatic and timely detection of these patients can be one of the most important tasks in the complex of measures aimed at protecting patients from stroke. The European Society of Cardiology's 2020 guidelines suggest the use of a CC to ABC patient management strategy. This strategy involves a number of measures aimed at managing atrial fibrillation, including confirming the diagnosis, determining the characteristics of atrial fibrillation and treatment tactics. One of the points of this strategy is the control of comorbidities and risk factors for cardiovascular diseases. To date, rivaroxaban has a number of convincing and reliable data on a high profile of efficacy and safety in the treatment of comorbid patients who not only have a high risk of stroke, but also need protection from coronary events and decreased renal filtration function. These data are confirmed by both the results of randomized clinical trials and data from real clinical practice. The review discusses the literature data describing the condition of patients with atrial fibrillation while taking direct oral anticoagulants, according to the search query “Atrial fibrillation, effectiveness and safety of rivaroxaban, warfarin, comorbidity, atrial fibrillation, efficacy and safety of rivaroxaban, warfarin, comorbid status” for the period from 2010 to 2020 in open sources PubMed and e-library, and a strategy for the comprehensive protection of patients with atrial fibrillation when using rivaroxaban is proposed for consideration.


303-309 33

Intracerebral hemorrhage (ICH) is severe and fatal complication of anticoagulant therapy with an incidence 0.3-0.7% per year. For patients with atrial fibrillation (AF) anticoagulants are administered for decreasing risk of stroke and systemic embolism. In this case the occurrence of intracranial bleeding is hard task for doctor. From the one side it is necessary to reverse the action of the drug for preventing the growth of hematoma. At the same time the discontinuation of therapy increases the risk of systemic embolism for patients with AF significantly. Clinical guidelines and studies have been reviewed about ICH during anticoagulant therapy. Nowadays there is no quality evidence about reversal of anticoagulant effects after ICH and optimal time of resumption of anticoagulant therapy. Firstly, we do not have large randomized controlled trials on this issue. The majority of clinical guidelines were based on retrospective studies and opinions of experts. Soon several randomized controlled trials will be finished and new data will be presented.

310-314 38

At the end of 2020, a new term “post-COVID-19 syndrome” appeared in the medical community. The prevalence of this syndrome reaches more than 30% among patients who have had COVID-19, and its duration can vary from 12 weeks to 6 months. One of the most severe consequences of COVID- 19 is the defeat of the cardiovascular system, which has a variety of mechanisms: dysregulation of the renin-angiotensin-aldosterone system; pathological systemic inflammatory response; direct action of the virus on the myocardium with the development of myocarditis; respiratory failure with hypoxia, leading to damage to cardiomyocytes; microvascular damage due to hypoperfusion, increased vascular permeability, angiospasm and the direct damaging effect of the virus on the endothelium of the coronary arteries; thrombotic complications due to the procoagulant and prothrombogenic effect of systemic inflammation. One of the most promising directions in the treatment and prevention of damage to the cardiovascular system in patients with hypertension who have undergone COVID-19 is the appointment of antihypertensive drugs that have the most pronounced organoprotective properties together with statins. The single pill combination of lisinopril, amlodipine and rosuvastatin is an effective drug that allows achieving not only adequate hypotensive and lipid-lowering effects, but also due to its pronounced organoprotective properties, to expect a reduction in cardiovascular risk and complications in patients who have suffered a new coronavirus infection caused by the SARS-CoV-2 virus.

315-322 26

Vasovagal syncope (VVS) can occur in every third of human population. Clinical symptoms of VVS areas a result of arterial hypotension with critical global cerebral hypoperfusion due to vasodilatation and bradicardia. Bradicardia is manifested as sinus node dysfunction and atrioventricular conduction disturbances due to activation of nervus vagus. Asystole can take place in some cases. Lack of efficacy of permanent pacemaker founds in patients to prevent of VVS. The results of double blind placebo controlled studies, European and American expert's opinions, probable causes of lack of efficacy of pacemakers in such category of patients and way of solution of this problem are discussed in the review. Syncope recurrences in spite of pacemaker implantation, risk of surgery complications and good life prognosis are arguments for therapeutic approach, now suitable for the most of patients with VVS. Case report (VVS with asystole but without of pacemaker implantation) with successful follow-up is analyzed in the article.

323-331 31

The current understanding of the management of patients with diabetes mellitus (DM) based on the concept of the cardiovascular continuum involves not only the prevention and treatment of cardiovascular diseases (CVD), but also the prevention and treatment of chronic kidney disease (CKD). The fact is that patients with DM and CKD represent a special group of patients with a very high risk of CVD and cardiovascular mortality. Such patients require early diagnosis and timely identification of risk factors for the development and progression of CKD for their adequate correction. Arterial hypertension, along with hyperglycemia, is the main risk factor for the development and progression of CKD in patients with diabetes. In this regard, the choice of antihypertensive therapy (AHT) in patients with diabetes is of particular importance. The basis of AHT in diabetes and CKD is the combination of a blocker of the renin-angiotensin-aldosterone system (an angiotensin-converting enzyme inhibitor [ACE inhibitor] or an angiotensin II receptor blocker [ARB]) and a calcium channel blocker (CCB) or a thiazide / thiazide-like diuretic. The task of the performed AHT is to achieve the target level of blood pressure (BP). At the same time, the optimal blood pressure values in patients with diabetes and CKD are blood pressure values in the range of 130-139/70-79 mm Hg. If the target blood pressure is not achieved, it is necessary to intensify antihypertensive therapy by adding a third antihypertensive drug to the therapy: CCB or a diuretic (thiazide / thiazide-like or loop). In case of resistant hypertension, it is necessary to consider the possibility of adding antagonists of mineralocorticoid receptors, other diuretics or alpha-blockers to the conducted AHT. Beta-blockers can be added at any stage of therapy if the patient has exertional angina, a history of myocardial infarction, atrial fibrillation, and chronic heart failure. The need to normalize blood pressure parameters by prescribing combined antihypertensive therapy in patients with diabetes and CKD is explained by a decrease in renal and cardiovascular risks, and, therefore, a decrease in the risk of mortality in this cohort of patients.

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Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice that affects intracardiac hemodynamics and is accompanied by increased mortality due to the risk of stroke and systemic thromboembolism. In recent years, numerous studies, evaluating the use of biomarkers in AF patients, have been conducted to expand the possibility of stratification the complications risks.

The aim of the review is to evaluate the possible isolated and combined predictive significance of NT-proBNP, troponin T (TnT) and D-dimer levels in the development and progression of AF and its thromboembolic complications according to published data. Determining the level of NT-proBNP can be used to diagnose cardioembolic stroke in latent forms of AF. Patients with a cardioembolic stroke have been shown to have higher BNP/NT-proBNP levels than patients with an atherothrombotic stroke and venous thromboembolism. Elevated TnT level is independently associated with AF detection as a cause of stroke. The assessment on the CHADS2 scale significantly correlates with the level of troponin I (TnI). However, it is equally important to take into account TnI level even with a low score of CHADS2. Patients with the level of TnI ≥ 0.040 pg/L are considered to be prescribed anticoagulants in the same way as the patients with high CHADS2 score. Similar results were obtained analyzing high-sensitivity cardiac troponin T (hs-cTnT) data. The level of D-dimer 0.315 mg/L was determined to be the optimal limit level for predicting the adverse functional outcome of stroke owing to AF. Patients with a high level of D-dimer have shown a high risk of developing thromboembolic and cardiovascular complications despite their taking anticoagulant drugs. D-dimer levels positively correlate with the CHA2DS2 and CHA2DS2-VASC scales of stroke risk stratification. The analysis of the biomarkers combination has revealed the increase of hs-cTnT and BNP associated with stroke in AF patients (p<0.05). However, ABC scale, including hs-cTnT and NT- pro BNP, hasn't given more accurate result in stroke predicting than CHA2DS2-VASc scale. The integration of biomarkers in predicting the risk of AF occurrence, progression and appearance of thromboembolic complications is a promising direction. An isolated level of biomarkers (hs-cTnT, NT-proBNP, D-dimer) and their combination with clinical risk factors can improve the quality of cardioembolic strokes prognosis.

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Chronic heart failure (CHF) occurs in 4.3-28% of patients with diabetes mellitus and is most often associated with the presence of coronary heart disease, arterial hypertension and the direct adverse effects of insulin-resistance, hyperinsulinemia and hyperglycemia on the myocardium. Diabetes mellitus occurs in 12-47% of patients with CHF and can develop within several years after a diagnosis of HF in 22% of patients due to insulin-resistance of failure tissues. The presence of diabetes mellitus leads to a greater severity of clinical symptoms and hospitalization rate, worsening of quality of life and prognosis in CHF. A decreased left ventricular ejection fraction is an independent predictor of the poor prognosis in the patients with diabetes mellitus. The algorithm of the treatment of CHF in the patients with and without diabetes mellitus is not fundamentally different, but it requires taking into account the metabolic effects of the prescribed drugs. Angiotensin receptor-neprilysin inhibitor are increasingly used in clinical practice and are gradually replacing angiotensin-converting enzyme inhibitors and sartans in CHF both without diabetes mellitus and in its presence. Recently, the effectiveness of type 2 sodium glucose cotransporter inhibitors has been proven in patients with CHF with and without diabetes mellitus. This review is devoted to the relationship of diabetes mellitus and CHF, as well as the approaches to the management of such comorbid patients.





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