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 1 (2021)
View or download the full issue PDF (Russian)


4-10 145

Aim. To characterize patients accessing lipid clinic and assess the efficiency of treatment in a specialized medical center.

Material and methods. A retrospective analysis of the surviving medical records of outpatients who visited the lipid clinic of the National Research Center for Therapy and Preventive Medicine (Moscow, Russia) in 2011-2019 (n=675) was carried out. Cardiovascular risk (CVR) and target lipoproteins levels were evaluated in accordance with actual guidelines for the diagnostics and correction of dyslipidemias.

Results. The mediana of lipid clinic patients age was 57 [46;65] years. Female persons attend lipid clinic more often (61.5%). 48.5% of patients had low density lipoprotein cholesterol (LDL-c) >4.9 mmol/L, 7.7% had triglycerides level >5.5 mmol/L. Most of the patients were diagnosed with type IIa hyperlipidemia (44,1%) or type IIb (28,0%). Inherited impaired lipid metabolism was diagnosed in 27.7% individuals. 12.7% of the patients had familial hypercholesterolemia, 57.4% – had secondary causes of impaired lipid metabolism. More than half of the patients (52.4%) had low or moderate CVR, 28.1% had a very high CVR. High or very high CVR individuals revisited the lipid clinic more often than people with lower risk (68.2% vs. 35.4%). Revisiting patients (25.4%) reached LDL-c targets more often (33.3% of very high CVR patients; 45.5% of moderate-risk people) than in ordinary outpatient practice. High-intensity statin therapy was recommended for 32% of patients, and combined lipid-lowering therapy – for 14.8%. Among very high CVR individuals, combined lipid-lowering therapy was prescribed for 38.5%. Given the lipid-lowering therapy prescribed in the lipid clinic, LDL-с<1.8 mmol/L and<1.5 mmol/L will be achieved at 40.7% and 32.9% of patients with very high СVR.

Conclusion. Lipid clinic is an important part of the medical care system for long-term follow-up of patients with impaired lipid metabolism, and it is more efficient in achieving target values of lipids and correcting risk factors in comparison with the primary medical service.

11-15 141

Aim. To study the prognostic value of the ORACLE risk score for assessing the risk of bleeding in patients with acute coronary syndrome (ACS) undergoing anticoagulants for atrial fibrillation using the combined database of the ORACLE II and RECORD 3 registers.

Material and methods. This analysis included patients with ACS from 2 observational studies: ORACLE II (ObseRvation after Acute Coronary syndrome for deveLopment of trEatment options; n=1803) and the RECORD-3 register (n=2370). In total, the database included 4173 patients, of which 246 (6.08%) received oral anticoagulants for atrial fibrillation. The mean age of patients was 64.7±11.9 years, 2493 (59.7%) were men. Hemorrhagic risk was assessed using the ORACLE, CRUSADE, ORBIT, and HAS-BLED risk score.

Results. Patients receiving anticoagulant therapy were older (69.9±11.3 years and 64.0±12.2 years, p<0.001). Among these patients there was a larger proportion of women, and a smaller proportion of patients with ACS with ST elevation, they were more likely to have chronic heart failure, chronic kidney disease, history of stroke. Among patients receiving anticoagulants and included in the ORACLE study, the frequency of percutaneous coronary intervention was higher than in patients included in the RECORD study. In the joint database, 71 significant bleeding was recorded during the hospitalization period – 64 (1.7%) in patients without anticoagulants and 7 (2.8%) among patients taking anticoagulants (p=0.06). Over 6 months, among patients who did not receive anticoagulants, there were 97 cases of bleeding (in 2.6% of patients), in the group of patients receiving anticoagulants – 12 cases of bleeding (4.9%) – the differences in frequency were significant (p=0.029). The ORACLE risk score had the greatest prognostic value (area under the ROC curve 0.874±0.0416, sensitivity 82.7%, specificity 79.1%). The predictive value of the HAS-BLED risk score was slightly lower (area under the ROC curve 0.710±0.0360, sensitivity 63.2%, specificity 56.8%). The value of the CRUSADE risk score (area under the ROC curve 0.612±0.0269, sensitivity 53.7%, specificity 59.5%) and ORBIT risk score (area under the ROC curve 0.606±0.0457, sensitivity 62.5%, specificity 58.3%) were lower (p<0.001 for all scales).

Conclusion. The use of the ORACLE bleeding risk score can be recommended for patients with ACS requiring anticoagulant therapy.

16-22 120

Aim. To study the relationship between the levels of synthesis of reactive oxygen species (ROS) by platelets and neutrophils in patients with coronary heart disease (CHD) before and after coronary artery bypass grafting (CABG), depending on sensitivity to acetylsalicylic acid (ASA).

Material and methods. The study included 95 patients with coronary artery disease who are indicated for CABG surgery. The control group consisted of 30 healthy donors. The antiplatelet therapy was stopped for at least 5 days before CABG. In the postoperative period, from the first day, all patients were received 100 mg of an enteric form of acetylsalicylic acid (ASA). Resistance to ASA was determined at the level of platelet aggregation with arachidonic acid ≥20% by optical agregometry at least at one observation point: before CABG, on 1-3 day and on 8-10 day after surgery. We evaluated the spontaneous and induced lucigenin-dependent chemiluminescence (CL) of platelets (ADP induction) and neutrophils (zymosan induction) by the exit time to maximum intensity (Tmax), maximum intensity (Imax) and area (S) under the CL curve.

Results. 70.5% sensitive (sASA) and 29.5% resistant (rASA) to ASA patients were revealed. Prior to CABG, in sASA patients, the Imax of spontaneous and zymosan-induced neutrophil CL and CL platelet activity was increased relative to control values. Tmax of spontaneous platelet CL, Imax and S under the ADP-induced platelet CL curve were lower in sASA patients, if to compare with rASA patients. On the 1st and 8-10th day after CABG in sASA patients, the CL indicators of neutrophil and platelet activity also remained elevated compared to control values. On the 1st day after CABG decreased levels of S under the spontaneous CL curve of neutrophils in rASA patients was established compared with sASA patients, and increased levels of Imax and S under the curve of induced neutrophil CL were detected in comparison with the control range. In rASA patients, the values of Tmax of spontaneous platelet CL decreased in relation to the values detected in the control group and sASA patients. On the 8–10th day after CABG, most indicators of spontaneous and zymosan-induced CL neutrophils in rASA patients were also increased compared to control values. In rASA patients a positive correlation of Imax-induced CL was found (r=0.83) on the 1st day after CABG and negative correlations of Tmax of spontaneous CL (r=- 0.75) and S under the curve induced CL (r=-0.70) on the 8-10th day were detected between platelets and neutrophils.

Conclusion. In sASA patients with coronary heart disease before and after CABG, a high level of synthesis of superoxide radical by neutrophils and platelets was detected. The relationship between the levels of the synthesis of superoxide radical by neutrophils and platelets was found only after CABG in rASA patients. Increased synthesis of superoxide radical due to metabolic and regulatory relationships in neutrophils and platelets stimulates pro-inflammatory processes in coronary artery disease and determines the sensitivity of platelets to ASA.

23-28 152

Aim. Supraventricular arrhythmias (SVA) are associated with high morbidity and mortality. However, little attention is paid to this condition in patients undergoing hemodialysis. The aim of this study was to analyze the long-term relationship of intradialytic SVA, including asymptomatic arrhythmias, with adverse events in a cohort of patients undergoing hemodialysis.

Material and methods. An observational prospective study was conducted in a group of patients on hemodialysis with a 10-year follow-up. The study involved 77 patients (42 men and 35 women; mean age 58±15 years) with sinus rhythm, then they were monitored for ECG for six consecutive hemodialysis sessions during recruitment.

Results. Arterial hypertension was present in 68.8% of patients, diabetes mellitus in 29.9% of patients. SVA were reported in 38 patients (49.3%); they all had a short-term, asymptomatic character and were terminated independently. Age (hazard ratio [HR] 1.04 per year; 95% confidence interval [CI] 1.00-1.08) and an increase of the atrium (HR 4.29; 95%CI 1.30-14.09) were associated with supraventricular arrhythmia in multidimensional analysis. During an average follow-up of 40 months, 57 patients died, and cardiovascular diseases were the main cause of death (52.6%). Variables associated with all-cause mortality in the Cox model were age (HR 1.04 per year; 95%CI 1.00-1.08), C-reactive protein (HR 1.04 per 1 mg/l; 95%CI 1.00-1.08) and supraventricular arrhythmias (HR 3.21; 95%CI 1.29-7.96). Patients with supraventricular arrhythmias also had a higher risk of nonfatal cardiovascular events (HR 4.32; 95%CI 2.11-8.83) and symptomatic atrial fibrillation during observation (HR 17.19; 95%CI 2.03-145.15).

Conclusions. Strong relationships have been established between the presence of supraventricular arrhythmias recorded during ECG during dialysis and symptomatic AF developing in the future. Patients with supraventricular arrhythmias had a larger right atrium. Age and supraventricular arrhythmias are the main variables associated with mortality in dialysis patients.

29-35 268

Aim. To study predictors of primary care physician adherence to guideline-recommended pharmacotherapy of stable coronary artery disease.

Material and methods. This pharmacoepidemiologic cross-sectional study was conducted in primary care setting of Moscow. 805 patients (mean age 68.9±9.9 years, males 51.4%) with established stable coronary artery disease (SCAD) were included. Demography, medical history, prescribed pharmacological treatment data were obtained. Physician adherence to guideline-recommended pharmacotherapy (GRP) of SCAD was evaluated based on the Class I guideline recommendations. Pharmacotherapeutic guideline adherence index (PGAI) was introduced as composite quality indicator, calculated in line with “all-or-none” rule and in regard with documented contraindications. To search for predictors of adherence the patient population was divided in two groups by level of physician adherence measured by PGAI. Statistical analysis was performed by IBM SPSS Statistics 16.0, the level of statistical significance was set at p<0.05.

Results. The prescription rates of essential drug therapies of SCAD (regarding contraindications) were quite adequate: beta-blockers/calcium channel blockers – 90,1%, acetylsalicylic acid/clopidogrel/oral anticoagulants – 95,7%, statins/ezetimibe – 86,3%, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers – 87,6%. 82,9% (n=667) of patients were prescribed treatment for SCAD in compliance with the guidelines. Suboptimal pharmacotherapy was identified in 17,1% (n=138) of patients. These groups were similar in sex distribution (males 50,4 vs. 56,5%; p=0,188). Mean age tended to be lower in GRP adherent group (68,5±9,9 vs. 70,6±10,0 years; p=0,052). Bivariable analysis showed that good adherence to guideline-recommended pharmacotherapy was associated with higher prevalence of stable angina (66,4 vs. 53,6%; p=0,004), arterial hypertension (93,3 vs. 79,7%; p<0,001) and dyslipidemia (21,4 vs. 9,4%; p<0,001) and with lower prevalence of myocardial infarction (48,1 vs. 67,4%; p<0,001). Logistic multivariable regression model (gender, age, 6 medical history variables) identified 6 patient-related factors that were significantly associated with physician adherence to guideline-recommended pharmacotherapy: age (odds ratio [OR] 0,97; 95% confidence interval [CI] 0,95-0,99; p=0,009), arterial hypertension (OR 3,89; 95%CI 2,19-6,90; p<0,001), dyslipidemia (OR 2,31; 95%CI 1,23-4,34; p=0,009), chronic heart failure (OR 1,95; 95%CI 1,06-3,61; p=0,032), revascularization (OR 2,14; 95%CI 1,33-3,45; p=0,002), myocardial infarction (OR 0,28; 95%CI 0,16-0,48; p<0,001).

Conclusion. Primary care cardiologist adherence to guideline-recommended pharmacotherapy of SCAD was satisfactory evaluated as 82,9% by composite indicator PGAI. Arterial hypertension, heart failure, dyslipidemia и revascularization were predictors of better physician adherence. History of myocardial infarction and older age were risk factors of non-adherence. Identification of patient-related factors associated with underperformance may facilitate tailoring quality improvement interventions in primary care of coronary patients.

36-41 98

Aim. To study the presence and nature of correlations between the level of transforming growth factor β1 (TFR-β1) and structural and functional parameters of the heart in the development of myocardial remodeling and fibrosis in patients with chronic heart failure (CHF) of ischemic origin.

Material and methods. The study included 120 men with class II-IV CHF who have history of myocardial infarction, which are divided into 3 groups depending on the CHF class. The control group included 25 healthy men. Assessment of left ventricular (LV) structural-functional state was carried out by echocardiography. Investigation of TFR-β1 and N-terminal precursor indices of cerebral natriuretic peptide (NT-pro BNP) was performed by enzyme immunoassay.

Results. Patients with class II-IV CHF were hyperexpression of ТФР-β1, the levels of which increased significantly as NYHA class increased and CHF progressed. The most significant structural-geometric rearrangement of LV and hyperactivation ТФР-β1 recorded in patients with class IV CHF (77.2±6.33 ng/ml with class IV CHF versus 46.7±3.74 ng/ml and 58.9±4.75 ng/ml with class II and III CHF; р< 0.05). In patients of class III-IV CHF, correlation relationships between ТФР-β1 level and echocardiographic parameters (LV myocardial mass index are established: r = 0.56, p = 0.05; end systolic volume index: r = 0.52, p = 0.05; value of LV ejection fraction: r = -0.48, p=0,05). Significant direct relationships are established in patients with class III-IV CHF between ТФР-β1 level and NT-rgo BNP levels (r=0,44; р=0,05).

Conclusion. The intensity of myocardial remodeling and fibrosis processes in patients with a progressive course of CHF is related to ТФР-β1 hyperexpression and is associated with a high level of activity of natriuretic peptides.


42-48 106

Aim. To study the relationship of modifiable risk factors (RF) with indicators of arterial stiffness and vascular age based on the contour analysis of the pulse wave velocity in hypertensive patients.

Material and methods. The material of the study was the data from a survey of patients undergoing clinical observation at the polyclinic of MMC SOGAZ. A total of 107 patients were examined, in which 70 were men and 37 were women. The average age was 52.3±18.29. Photoplethysmography was used as a special research method, performed using the AngioScan-01 diagnostic complex. The main indicators used to evaluate the stiffness of large vessels were: stiffness index (SI), reflection index (RI), augmentation index (Alp75), age index (AGI), pulse wave types (PV) and vascular age (VA).

Results. The mean values of arterial stiffness indices in patients with essential arterial hypertension (AH) and healthy individuals (control) had significant differences. The mean SI, Alp75, and VA values in the group of patients with AH were 7.8±1.03, 7.0±14.44 and 50.8±15.93 versus 7.2±1.73, 0.5±18.02 and 43.8±16.94, respectively (p< 0.05). In both groups, a strong inverse correlation of passport age with C-type PV was revealed (r=0.74, p< 0.01), which reflected the dynamics of a gradual age-dependent decrease in vascular compliance. The average VA value in the control group was 63.1±16.99 years with an average passport age of 59.5±8.79 years, which significantly differed from VA in hypertensive patients (p< 0,05). Overweight, hypercholesterolemia, elevated low-density lipoprotein levels, lack of adequate antihypertensive control, and left ventricular diastolic dysfunction were significantly associated with early vascular (arterial) aging.

Conclusion. Patients with hypertension, in addition to high blood pressure, significantly differ from normotensive control in terms of arterial stiffness. The lack of control over modifiable RF of patients with hypertension is associated with early vascular aging.

49-55 248

Aim. To study adherence to recommended treatment, additional clinical and economic benefits of a titration-free statin therapy regimen.

Material and methods. Ambulatory patients (n=300) with a high or very high risk of hypercholesterolemia who have indications for statin treatment for primary or secondary prevention of cardiovascular diseases is included in a non-randomized trial. Patients are divided into 2 groups. Group 1 had a titration regimen of statins in accordance with current recommendations (group 1A [n=50] – primary cardiovascular prevention; group 1B [n=100] – secondary cardiovascular prevention). Group 2 received a titration-free statin regimen in fixed doses (group 2A [n=50] – primary cardiovascular prevention; group 2B [n=100] – secondary cardiovascular prevention). Patients were prescribed atorvastatin (10-80 mg/day) or rosuvastatin (10- 40 mg/day). Group 1 patients had visits to the doctor after 1, 3, 6 and 12 months from the start of statin use, group 2 patients after 3 and 12 months. Treatment adherence, effects on surrogate and hard endpoints, and cost-effectiveness of the two statin regimens were evaluated.

Results. The target level of low-density lipoprotein cholesterol (LDL-C) after 12 months in group 2 was achieved in 56.4% of patients versus 53.4% in group 1. The average level of LDL-C decreased by 1.84±0.44 mmol / l in group 2 versus a decrease of 1.61±0.47 mmol / L in group 1. The costeffectiveness ratio was 9658.72 rubles in group 2 versus 8341.73 rubles in group 1 for a 1 mmol / l LDL-C level decrease in 1 patient within a year. An increase in annual costs per patient in group 2 compared with group 1 by 75.76 rubles reduced the relative risk of developing a combined endpoint by 1% per year.

Conclusion. The use of a titration-free statin treatment regimen allowed us not only to more effectively control of LDL-c levels in patients with high and very high cardiovascular risk compared to the traditional statin therapy regimen, but also to obtain economic advantages in patients with high and very high cardiovascular risk.

56-61 87

Aim. To compare clinical features, drug therapy and outcomes in patients with non-obstructive and obstructive coronary artery infarction.

Material and methods. The study included 206 patients with a diagnosis of myocardial infraction (MI). According to the results of coronarography, patients were divided into two groups: 103 patients (group 1; MINOCA) did not have obstructive involvement coronary arterial (CA): in 67 (65%) of cases, there is no data for atherosclerotic coronary bed lesion, another 36 (35%) – have CA stenosis up to 50%. 103 patients (group 2) with MI and obstructive CA (MIOCA). The patients of the second group in 100% of cases underwent endoprosthesis of CA, the affection of which caused infraction. The second group was selected by the copy method comparatively to the first group. The analysis of clinical peculiarities, medication and outcomes was made in these groups of patients, in particular.

Results and conclusions. The clinical “portrait” of patients with MI in nonobstructive and obstructive CA involvement did not differ significantly. Higher serum level of total cholesterol (5.6 [4.4;6.2] vs 5.1 [4.4;5.8] mmol/l р=0.04) and cholesterol of low-density lipoproteins (2.9 [2.2;3.5] vs 2.5 [2.1;2.9] mmol/l р=0,01), troponin [2.8 [0.7;15.0] vs 1.2 [0.1;7.7] ng/ml р=0.02) were identified in blood tests of MIOCA patients in the comparison with MINOCA group. Antero-lateral (р=0.02) and unspecified localization of MI (р=0.03) was more frequent in the MINOCA group. The differences in therapeutic approach were manifested in the more frequent prescription of double antiplatelet therapy: (99.0% vs 80.6% р< 0.01) in MIOCA patients. In the MINOCA group а more frequent prescription of dihydropyridine calcium channel blocking agents was registered (23.3% vs 2.9% р<0.01). The unfavorable outcomes for MINOCA is comparable to MIOCA in terms of the incidence of hospital mortality (2.9% against 4.9%; p>0.05), annual mortality (5.1% against 7.8%; p>0.05), and combined endpoint (6.8% against 10.7%; p>0.05).

Conclusion. Despite the similarity of the clinical presentations of MI with obstructive and nonobstructive CA involvement in real clinical practice, there are differences in the pharmacotherapeutic approach in the management of these groups of patients. MINOCA is characterized by an unfavorable outcomes similar to MIOCA.


62-72 113

Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. Oral anticoagulation for stroke prevention is therefore recommended in patients with atrial fibrillation and decreased renal function. Each direct oral anticoagulant has unique pharmacologic properties of which clinician should be aware to optimally manage patients. The doses of direct oral anticoagulants require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault equation, should be used to estimate glomerular filtration rate in patients with atrial fibrillation treated with direct oral anticoagulants. Our review tries to find arguments for benefit of direct oral anticoagulants in patients with renal dysfunction.


73-82 101

The present work is devoted to the analysis of modern publications on various aspects of the development and course of ischemic stroke in the presence of acute myocardial infarction. A literature search was conducted on the websites of cardiological and neurological societies, as well as on the PubMed, EMBASE, eLibrary databases using the keywords: myocardial infarction, acute coronary syndrome, stroke, acute cerebrovascular accident, myocardial infarction, acute coronary syndrome, stroke. The authors of this review found that although stroke is a relatively rare complication of myocardial infarction, its prevention is an extremely significant task, since it is associated with high mortality, disability and a significant increase in the cost of treatment. So, it is extremely important to detect thrombosis of the left ventricular cavity in a timely manner, to register preexisting atrial fibrillation that occurs earlier or for the first time, followed by the appointment of anticoagulant therapy. Timely reperfusion treatment, the use of statins and modern dual antithrombotic therapy can reduce the risk of developing cerebrovascular accident in patients with myocardial infarction. It is likely that a decrease in the activity of subclinical inflammation after myocardial infarction will also reduce the risk of stroke, as was recently shown in the COLCOT study. Currently, it remains relevant to search for new knowledge about the risk factors for stroke, which complicated the course of myocardial infarction, which will allow developing more effective and personalized preventive measures in a patient with acute coronary syndrome.

83-91 87

Multifocal arterial disease is common in patients with atherosclerotic cardiovascular disease and is associated with an increased risk of cardiovascular complications and death. The possibility of improving the prognosis of patients with multifocal arterial disease is associated with a more efficient diagnosis of both the underlying disease and obstructive atherosclerotic lesions of other localizations and with a more intensive secondary prevention. According to observational studies, the presence of significant stenoses of the carotid arteries and, especially, lower extremities arterial disease can be predictorы of similar lesions in other vascular beds and their detection with screening methods available in clinical practice allows improvement of the diagnosis in patients with suspected coronary artery disease. On the other hand, screening of lower extremities artery diseases in patients with acute coronary syndrome can clarify indications for the use of invasive diagnostic and treatment strategy, in patients with chronic coronary artery disease it can justify more aggressive approaches to secondary prevention.

92-98 90

The review demonstrates the main aspects of seasonal cardiovascular mortality. Climatic factors, including seasonal weather changes, have a significant impact on the biosphere. People are also characterized by the seasonal dynamics of the activity of many organs and systems, biochemical parameters, and mortality. Cardiovascular mortality is also characterized by seasonal fluctuations: in winter it is maximum, in summer it is minimal. The same patterns are characteristic of mortality from cardiovascular diseases (myocardial infarction, stroke, cardiac arrhythmias, etc.). The article presents the basic patterns of seasonal cardiovascular mortality in various climatic zones, the cardiovascular mortality of countries located in the equatorial and subequatorial climatic region. In addition, the mortality displacement phenomenon, the paradox of winter mortality. The main trends in changes in cardiovascular mortality over a long period of time are demonstrated. The paper discusses some of the mechanisms that underlie the dynamics of cardiovascular mortality during the year: seasonal fluctuations in the level of vitamin D, lipids in the blood plasma, changes in hemodynamic parameters, the effects of microbial and viral infections in the cold season, etc. In addition, data on seasonal the dynamics of risk factors for cardiovascular diseases is considered: an increase in body weight, a physical activity decrease, a change in the nutrition structure in the winter, the seasonal dynamics of depression, anxiety, hostility, the relationship of seasonal cardiovascular mortality with socio-economic, demographic and other factors. In conclusion, the main ways of development and prevention of seasonal CV cardiovascular mortality M, taking into account modern technologies at the international level, for state health departments, for specific patients, are demonstrated.


99-104 223

The new coronavirus infection (COVID-19) pandemic and the subsequent quarantine measures, particularly home isolation of the population, could have seriously affected the quality of pharmacotherapy and adherence to it by patients with chronic non-communicable diseases.

Aim. To assess the dynamics of adherence to pharmacotherapy by patients with stable coronary artery disease (SCAD) in self-isolation during the COVID-19 pandemic.

Material and methods. To accomplish the aim of the study, we selected 39 patients with SCAD who previously completed the ALIGN study, the purpose of which was to align patients’ medical therapies according to current clinical guidelines. From May 05, 2020, to May 14, 2020, a telephone survey was conducted of 39 patients with SCAD (37, 94.8%) males, mean age 67.6±8.5 years). After one year of participation in the ALIGN study, 87.1% of the patients were adherent to their prescribed pharmacotherapy. Adherence (overall and to specific medications) was assessed by means of the original adherence scale, which made it possible to identify violations in taking medications (non-adherence to the intake regime or discontinued intake of medications), and the main reasons for adherence violation were established. Adherence registered during the telephone survey at the time of the COVID-19 pandemic was compared to that obtained during the last time the patient participated in the ALIGN study.

Results. During the period of home isolation, a substantial decline in the adherence of patients to pharmacotherapy was revealed. The percentage of adherent patients decreased from 87% to 54% due to an increase in the number of patients who stopped taking several or all of the recommended drugs during home isolation (p=0.024). The overall rate of adherence during the COVID-19 pandemic appeared to be even worse than before the start of the ALIGN study. A comparative analysis of subgroups with and without a decline in adherence revealed a trend suggesting that higher patient education (p=0.067) or previous percutaneous coronary intervention (p=0.063) can be considered a protective factor associated with fewer violations in adherence during the COVID-19 pandemic. Analysis of adherence to specific drugs showed that during self-isolation there was a decrease in adherence to antiplatelet drugs (p=0.047) and to statins (p=0.055). Adherence to beta-blockers, renin-angiotensin-aldosterone system inhibitors and dihydropyridine calcium antagonists remained unchanged.

Conclusion. In patients with SCAD during the period of home isolation in the COVID-19 pandemic and associated difficulties in contacting the attending physician, there was a decline in adherence and an increase in the number of patients who stopped taking several or all prescribed drugs.


105-110 147
Friedreich's disease is a hereditary neurodegenerative multiple organ disease, primarily affecting the most energy-dependent tissues (cells of the nervous system, myocardium, pancreas), the lesion of which is characterized by progressive ataxia, dysarthria, dysphagia, oculomotor disorders, loss of deep tendon reflexes, pyramid signs, diabetes mellitus, visual impairment. Friedreich's ataxia is the most common of all hereditary ataxias; nevertheless, this disease is considered orphan. By its pathogenesis, Friedreich's disease is mitochondrial ataxia, caused by a deficiency in the transcription of the FXN gene, leading to a decrease in the synthesis of the frataxin protein. Frataxin is a protein associated with the inner mitochondrial membrane, which in turn is involved in the formation of iron-sulfur clusters, the lack of which leads to a decrease in the production of mitochondrial ATP, an increase in the level of mitochondrial iron and oxidative stress. The basis of the clinical picture of Friedreich's disease is ataxia of a mixed (sensitive and cerebellar) nature. The steady and gradual progression of neurological symptoms significantly affects the quality of life of patients and is most often the leading reason for seeking medical attention. However, the prognosis is primarily due to the involvement of cardiac tissue in the pathological process. The main causes of death in patients with Friedreich's ataxia are severe heart failure and sudden cardiac death due to cardiomyopathy. The overwhelming majority of foreign and domestic publications on Friedreich's ataxia are devoted to the neurological manifestations of this disease, and little attention is paid to this problem in the cardiological scientific and practical society. The purpose of this review is to provide up-to-date information on modern methods of diagnosing myocardial damage at various stages of Friedreich's disease.
111-118 74

Bicuspid aortic valve refers to common (0.5-2% of the population) congenital heart defects that are asymptomatic throughout life, with valve dysfunction and/or aortopathy (pathia- from Greek pathos disease), manifested by expansion, aneurysm or dissection of the vessel. The pathogenesis of the formation of a bicuspid valve is unknown, a genetic component is noted, since the defect develops as sporadic, familial, in combination with other congenital heart defects and with hereditary connective tissue disorders. Morphogenetic studies suggest that different phenotypes of bicuspid aortic valve can be considered as etiologically different diseases, with valve dysfunction or valve dysfunction and aortopathy. Aortic lesion is characterized by phenotypic heterogeneity due to genetic or hemodynamic features. Researchers are discussing the relationship between the phenotype of the bicuspid aortic valve and aortopathy to predict the course of the disease and select the optimal surgical treatment technique. Diagnosis of heart disease is based on the results of an echocardiographic study, magnetic resonance imaging. Surgical treatment is performed for significant hemodynamic disturbances resulting from insufficiency or stenosis of the aortic valve, in cases of infective endocarditis, the risk of which is high, with aneurysm or aortic dissection.

119-123 81

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.


124-132 70

Arterial hypertension (AH) remains one of the main causes of disability and death worldwide, including in Russia. At the same time, the risks of coronary and cerebrovascular events increase in the presence of additional risk factors. The most common modifiable risk factors are metabolic disorders, including pre-diabetes, dyslipidemia, peripheral arterial atherosclerosis, and obesity, which also imposes certain features on the choice of optimal pharmacotherapy. Currently, the terminology of comorbid conditions continues to be discussed depending on their pathogenesis and the presence or absence of dominance of one disease over others, i.e. polymorbidity, comorbidity and multimorbidity. At the same time, “associative polymorbidity” is distinguished with a certain set of diseases that often occur in conjunction with each other with individual susceptibility of the body. One of the most common phenotypes of polymorbidity occurring in all age groups in both sexes is cardiometabolic, which is based on the formation of insulin resistance, sympathetic overactivity and chronic inflammation. This article provides a clinical example of the use of a fixed combination of angiotensin II receptor blocker telmisartan and calcium channel blocker amlodipine with the addition of an I1-imidazoline receptor agonist moxonidine in real clinical practice in a polymorbid cardiometabolic patient with target organ damage (left ventricular hypertrophy and microalbuminuria). High antihypertensive (favorable effect on 24-hour blood pressure, especially in the early morning) and organoprotective effectiveness of this combination, its possibilities in correcting additional risk factors (reduced heart rate, body weight and a positive effect on metabolic parameters), due to a synergistic effect on the central pathogenetic mechanisms of hypertension and obesity – insulin resistance and sympathetic overactivity.

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The article presents the history of the study and registration in the USSR of the buccal form of nitroglycerin (trinitrolong) in the 1970s and 1980s, based on a number of author's publications, documentary evidence and oral stories of participants in clinical trials. The specifics of the passage of the main stages of registration of a new pharmacological agent in the Soviet control and authorization system from the author's idea to the introduction of the drug into clinical practice are described. Some reasons for the lag of the USSR from the countries of the capitalist West in the development and introduction of new cardiac drugs are analyzed.

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Recent epidemiological studies have demonstrated that the development of a potentially reversible moderate acute kidney injury is associated with worsening clinical outcomes and an increased risk of death. This is especially true for patients with plural comorbidities who require procedures with IV radiopaque agents. This paper presents a clinical case of an elderly patient who requires coronary angiography, and who has common clinical conditions such as hypertension, multifocal atherosclerosis with the development of renal artery disease and the presence of a history of acute cerebrovascular accident and myocardial infarction, and chronic heart failure as well. Particular attention is given to assessing the risk of developing contrast-induced acute kidney injury in patients with cardiovascular disease, as well as discussing current views on the possibility of prescribing drugs that affect the reninangiotensin system in cardiac patients with concomitant renal artery disease.

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Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.

Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.

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Advances in the diagnosis and treatment of patients with infectious endocarditis are limited by the high frequency of cases with an unknown etiology and imperfection of microbiological (cultural) methods. To overcome these problems new approaches to the identification of infectious endocarditis pathogens were introduced, which allowed achieving certain positive results. However, it should be noted that despite the wide variety of diagnostic tools currently used, there is no ideal method for etiological laboratory diagnosis of infectious endocarditis. The article discusses the features and place of immunochemical, molecular biological (MALDI-TOF MS, real-time PCR, sequencing, in situ fluorescence hybridization, metagenomic methods, etc.), immunohistochemical methods, and their advantages and limitations.

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The results of the international multicenter study EMPEROR-REDUCED were reviewed the on-line scientific meeting of Moscow experts on October 30, 2020. Some proposals and recommendations for further study of the cardiovascular and renal effects of empagliflozin and its use in clinical practice in patients with chronic heart failure with reduced ejection fraction were accepted.

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The meeting of the expert council of cardiologists-lipidologists, organized with the support of Novartis and dedicated to the discussion of the existing system of medical care for patients with familial hypercholesterolemia / mixed dyslipidemia, the modern evidence base for lipid-lowering therapy and the practical value of the strategy of early combined lipid-lowering therapy for doctors and these categories of patients was held in Moscow on November 11, 2020.




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