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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 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 (www.rpcardio.com) 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 15, No 6 (2019)
View or download the full issue PDF (Russian)

ORIGINAL STUDIES

768-778 138
Abstract

Aim. Estimation of the correlation of self-perceived health (SPH) with social and psychological environment, lifestyle and cardiovascular risk markers in middle-aged men.

Material and methods. A total of 301 men aged 41-44 years were examined. The study included clinical examination and interrogation using a standard form. Physical activity was estimated with the help of the International Physical Activity Questionnaires, the level of psychosocial stress – with the Reeder scale, signs of vital exhaustion with the Maastricht Questionnaire Vital Exhaustion Scale. To evaluate the mode and quality of life the questionnaire developed by I.A. Gundarev was used. All the examined people were divided in three groups according to the distribution of SPH rates by tertiles: the group 1 (from 7 to 60 scores) – bad health, the group 2 (61-79 scores) – satisfactory and the group 3 (80-100 scores) – good health.

Results. Parameters of the social and psychological environment of middle-aged men were the basic determinates of their health self-perception, at that majority of the indices of the quality and mode of life were independent of family material well-being. Bad SPH in middle-aged men was determined by such parameters as: increased blood pressure (BP), abdominal obesity, excessive alcohol consumption, psychosocial stress, vital exhaustion, low physical activity. Material wealth influenced systolic BP level, the waist/hips circumference ratio, a number of cigarettes per day and thus the SPH status. The most significant determinants of SPH were the level of personal happiness, nervous stress at work, support by family, sports activities, working conditions, total cholesterol level, satisfaction with own work.

Conclusion. When working on programs focused on public health improvement the social, psychological and behavioral determinants of health selfperception must be considered.

779-788 80
Abstract

Aim. To study the clinical outcomes (achievement of target blood pressure [BP]) and tolerability of antihypertensive and hypolipidemic therapy with fixed combinations of indapamide/perindopril, amlodipine/perindopril, amlodipine/indapamide/perindopril and rosuvastatin in patients with hypertension and high/very high cardiovascular risk in real clinical practice.

Material and methods. The study included 16,788 patients from 104 cities of the Russian Federation. The duration of observation was 12 weeks. All patients had three monitoring visits. BP level was measured twice during the visits: the arithmetic mean of the obtained parameters was calculated. The results of the study were analyzed and presented by descriptive statistics.

Results. The average age of the patients was 60.6±10.2 years; 42.2% of the patients were men and 57.8% women. Patients who demonstrated systolicdiastolic hypertension (BP>140/90 mm Hg) at the initial visit accounted for 73.9% (n=12,413) of the total number of participants. The average level of systolic BP at the inclusion into the study was 162.94±13.07 mm Hg, the level of diastolic BP was 93.43±8.61 mm Hg. As expected, the Russian population consists of over 90% of patients with very high (57%; n=9,586) and high (35.9%; n=6,022) additional cardiovascular risk. Despite the fact that the overwhelming majority of patients with hypertension had a high and very high additional risk, more than a third of patients received monotherapy to control their BP level (36.8%; n=6,182), while 13.8% of patients (n=2,321) had never received antihypertensive therapy before. According to the results of therapy with combination drugs based on perindopril, 92.7% of patients managed to reach the target BP levels of <140/90 mm Hg. After treatment the average level of systolic BP decreased from 162.94±13.07 mm Hg to 127.80±7.56 mm Hg, and the level of diastolic BP – from 93.43±8.61 mm Hg to 78.54±5.59. Adherence to the treatment in more than 97% of cases was recognized as very high and high. Only 10 adverse events were recorded on a large sample of patients during 12 weeks of treatment.

Conclusion. In the Russian population, 73.9% of patients with hypertension and high/very high risk do not achieve the target BP levels. Application of combined therapy based on fixed combinations with perindopril allows achieving effective BP control in 93% of patients with hypertension having high and very high risk during 12 weeks with good tolerability of treatment.

789-794 77
Abstract

Background. Early diagnostics of masked hypertension (MH) is one of the key problems in modern cardiology due to the association of this blood pressure (BP) phenotype with doubled cardiovascular risk in comparison with normotension (NT). The current hypertension guidelines list numerous conditions, when the ambulatory BP monitoring (ABPM) is desirable in patients with normal office BP. However this list does not represent clearly defined, agreed and approved indications for ABPM as a diagnostic tool for MH.

Aim. To develop a method of MH diagnostics for the use in routine clinical practice based on the comparing characteristics of patients with reproducible MH vs NT.

Material and methods. The patients were selected from two trials that used ABPM (n=1778). The selection criteria included age 40-79 years, office BP<140/90 mm Hg, the absence of “hypertension” diagnosis or antihypertensive drug intake, and available results of two examinations (winter and summer): standard questionnaire, information about family history, chronic diseases and drug intake, height, weight, office and orthostatic BP and ABPM. We used the following definition of MH: elevated ambulatory BP (24-hour ≥130 and/or 80 mm Hg, daytime ≥135 and/or 85 mm Hg, or nighttime ≥120 and 70 mmHg) registered at both visits.

Results. In total, 153 patients with reproducible (both winter and summer) BP phenotype were included: 127 with MH, and 26 with NT (mean age 49.1Ѓ}7.8 years, 36.1% males). In multivariate analysis, reproducible MH was associated with body mass index (β2.097; p<0.0001), office diastolic BP (β2.152; p<0.0001), orthostatic systolic BP (β1.031; p<0.023) and orthostatic heart rate (β0.773; p=0.19). These parameters were used in the original “MH coefficient” formula.

Conclusions. MH is often found in patients with normal and optimal office BP and without “hypertension” diagnosis. The method described in the article helps to detect MH with high probability and define the individual indications for ABPM. The MH phenomenon in the category of patients warrants further investigation.

795-801 84
Abstract

Aim. To study the effectiveness and benefits of blood pressure (BP) remote monitoring in outpatients with hypertension.

Material and methods. The study included 100 patients with a verified diagnosis of hypertension, who didn’t achieve target BP pressure levels. The patients measured their BP twice a day over 6 months with facilities with automatic data transmission over GSM-channel to a remote monitoring center. BP parameters were being transmitted online to the remote monitoring center, where they were being processed and transferred to the personal account planner (created by the Web interface based on the software and hardware complex) of the attending physician and operator of the remote monitoring center. It is important that doctor received information only on clinically significant measurement results, based on which he determined the urgency of contact with the patient and the further tactics of his management.

Results. No malfunctions in the work of communication facilities, technical failures in the software and hardware complex were registered over the entire period of the study. After 6 months of the monitoring it was possible to achieve target BP levels less than 135/85 mm Hg in 70% of patients. The proportion of patients with a high level of normal BP increased from 10% to 19%, while the proportion of patients with grade 1 and 2 of hypertension decreased significantly (from 33% to 7% and from 54% to 3%, respectively). At the beginning of telemedicine monitoring 3% of patients had stage 3 of hypertension, at the end of the study – 1%.

Conclusion. The technology of telemedicine monitoring has shown itself as a simple, affordable and reliable way of management of outpatients with hypertension in conditions of real clinical practice. It was possible to achieve BP levels less than 135/85 mm Hg in 70% of patients by the method of remote outpatient monitoring. BP remote monitoring changed fundamentally the decision-making strategy of the patients management: it was not the patient who independently determined the need for consultation with a medical professional, but the attending physician made a decision on the method and urgency of contact with the patient on the basis of the data of objective monitoring indicators.

802-805 72
Abstract

Aim. To study the safety of non-vitamin K oral anticoagulants (NOAC) in patients with atrial fibrillation (AF) over 75 years old.

Material and methods. The observation study included patients ≥75 years of age with confirmed AF, receiving dabigatran in a reduced dosage, apixaban or rivaroxaban in full or reduced dosage. Previous experience of NOAC treatment from the very beginning of therapy, if a patient was ≥75 years old, or from the point a patient reached 75 years was considered; episodes of NOAK change, as well as hemorrhagic and ischemic events associated with taking an anticoagulant, were recorded. Patient groups were comparable in risk score by CHA2DS2-VASc and HAS-BLED scales.

Results. Patients with AF (n=102; 39 men and 63 women; an average age 79.4Ѓ}4.1 years) were included: 32 patients were in dabigatran group, 34 patients – in apixaban group and 36 patients – in rivaroxaban group. 19 clinically significant bleedings were recorded, 10 occurred in patients taking dabigatran and 9 in those taking rivaroxaban. No hemorrhagic events in patients treated with apixaban were observed. Hematuria (31.6%), large subcutaneous hematomas (26.3%) and intensive nasal bleedings (26.3%) were the most frequent events. No ischemic cardioembolic stroke was recorded.

Conclusions. In elderly patients, all NOAC (dabigatran, rivaroxaban and apixaban) demonstrated good safety profile without major bleeding within a 1.5-year follow-up period.
806-812 69
Abstract

Aim. We aimed to study in real clinical practice the clinical and anamnestic characteristics, the peculiarities of double antiplatelet therapy (DAPT) prescription as well the incidence of ischemic and hemorrhagic events in patients with ST-elevated myocardial infarction (MI) during a year of follow-up, taking into account the baseline PRECISE-DAPT scores.

Material and methods. The study included 680 patients with MI from the database of Kemerovo observational registry for acute coronary syndrome (ACS). All the patients retrospectively underwent an individual calculation using the PRECISE-DAPT score. Then, depending on the number of the points, all the patients were divided into the low (less than 25 points) and high (25 or more points) risks groups. Differences in clinical and anamnestic parameters, the peculiarities of DAPT prescription, as well as the incidence of ischemic and hemorrhagic outcomes during a year of follow-up after MI were estimated in the groups.

Results. The Russian patients with ST-elevated MI and the high PRECISE-DAPT hemorrhagic risk score had a history of renal pathology (р=0.010), multivessel coronary artery disease and polyvascular disease (р=0.002), prior angina pectoris (р=0.001), as well as the course of the index event with the manifestations of acute coronary failure (р=0.001) more often than the patients from the low-risk group. The patients of the high-risk group less often underwent coronary angiography with stenting (р=0.001), as well as coronary artery bypass grafting (р=0.010) at hospitalization and had a higher in-hospital mortality rate (р=0.002). The patients at high hemorrhagic risk according to the PRECISE-DAPT score were less often prescribed with DAPT within a year after MI (р=0.001) and aspirin monotherapy was preferred more often (р=0.001). At the same time, the patients at high hemorrhagic risk on the PRECISE-DAPT score had more often major bleedings, recurrent MI and deaths (р=0.001) within a year after MI.

Conclusion. In the present study, the possibilities of risk assessment with the PRECISE-DAPT score were retrospectively tested on the sample of patients with MI from the ACS registry in Kemerovo city. Good identification of patients with the high risks of hemorrhagic events and ischemic outcomes within 12 months of the follow-up after index MI has been shown, which allows to recommend the PRECISE-DAPT score for a clinical practice in order to rationalize the approaches to DAPT prescription and to optimize the existing approaches to the comprehensive risk assessment of patients with ACS along with existing scales.

NOTES FROM PRACTICE

813-819 61
Abstract

Stress echocardiography is a modern widely used method of noninvasive diagnosis of coronary heart disease and stratification of the risk of cardiovascular complications. In addition, exercise echocardiography is an important tool to clarify the localization of ischemia and establish a symptomassociated artery for management of patient with known coronary angiography data. This is especially important in multivessel lesions, the presence of an occluded artery or borderline stenosis. Currently, various stress agents are used for stress echocardiography in clinical practice: pharmacological drugs (dobutamine or adenosine), transesophageal or endocardial pacing, treadmill, semi-supine bicycle. To detect signs of ischemia usually used only visual estimation of local contractility in the two-dimensional gray-scale mode. Modern modes of myocardial imaging, such as speckletracking echocardiography or three-dimensional visualization, are practically not used. In the presented clinical case, the possibility of combining standard and modern imaging modes to clarify the localization and quantification of ischemia in multivessel coronary lesions, including chronic artery occlusion, is shown. As a stress agent, a semi-supine bicycle was chosen, the use of which allowed to obtain a qualitative image of the left ventricular myocardium at rest and at peak load, suitable for assessing deformation and threedimensional visualization. Evaluation of left ventricular myocardial deformation by speckle-tracking echocardiography was more accurate than standard diagnosis in detecting signs of ischemia in a patient with multivessel lesions. Three-dimensional imaging was inferior in sensitivity to speckletracking stress echocardiography and, at present, seems to have more research value.

ASSOCIATED PROBLEMS OF CARDIOLOGY

820-830 83
Abstract

Chronic autoimmune inflammation is one of the leading risk factors for the development of chronic heart failure (CHF) in rheumatoid arthritis (RA). The purpose of the review is to analyze the results of investigations on the effects of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), biological disease-modifying anti-rheumatic drugs (bDMARDs), and targeted csDMARDs on cardiac function and the risk of developing CHF in patients with RA. Methotrexate may reduce the CHF risk and have a positive effect on the course of this condition in patients with RA. Despite the data on the presence of leflunomide effects that impede myocardial remodeling, there is no evidence of the role of the drug in the prevention of CHF in RA patients. Hydroxychloroquine may contribute to the prevention of CHF, but the risk of developing severe cardiotoxicity should be considered when taking the drug for a long time. Most studies have not revealed the negative effect of tumor necrosis factor inhibitors on the prevalence and incidence of new cases of CHF in RA patients, and an improvement in the structure and function of the heart during therapy has been shown. Inhibitors of interleukin (IL) -1, inhibitors of IL-6, inhibitors of T-cell co-stimulation, anti-B-cell therapy, targeted csDMARDs do not increase the risk of CHF and may have cardioprotective effects, including slowing the progression of left ventricle myocardial dysfunction. Due to the high risk of CHF and CHF-associated mortality in RA patients, early diagnosis of cardiac dysfunction, development of a prevention and treatment strategies are needed, including high-quality prospective studies to assess the effect of anti-rheumatic therapy on myocardial function, risk of developing and decompensation of CHF in RA patients. It is possible that some drugs may possess protective effects on cardiomyocytes so they could become the first-line drugs in patients with CHF or the risk of its development.

831-839 67
Abstract

Aim. To study the seasonal indicators of quality of life and control of bronchial asthma in hypertensive patients with bronchial asthma, observed by a cardiologist of the state outpatient institution.

Material and methods. Data from a prospective cohort study of hypertensive patients, some of which had bronchial asthma without exacerbation, were analyzed. Patients who were observed by a cardiologist at a state outpatient clinic took part in the study. There were other concomitant diseases that occurred in the participants, in addition to hypertension and bronchial asthma. Two groups of patients were formed: the control group (n=85) included patients with hypertension only, the main group (n=40) included hypertension and bronchial asthma. Patients had 3 visits: initial one, and after 6 and 12 months and then data on outcomes (30.1Ѓ}7.6 months of follow-up) were collected. The first and third visits included clinical measurements of blood pressure (BP), 24-hour BP monitoring, spirometry, clinical and biochemical blood tests, a standard survey, survey with questionnaires evaluating the control of bronchial asthma (Asthma Control Questionnaire; ACQ) and the patients quality of life (General Well-Being Questionnaire; GWBQ). The second visit included clinical BP and ACQ and GWBQ questionnaires. A comparison of the average indicators from the total number of observations carried out in winter, spring, summer and autumn periods has been performed.

Results. Hypertensive patients with/without bronchial asthma (n=125; 28 men, 97 women, average age 62.6Ѓ}8.8 years, duration of hypertension – 11.6Ѓ}8.6, duration of bronchial asthma – 9.3Ѓ}11.9 years) took part in the study. Outpatient BP levels throughout the study period were maintained at target values in both groups. It was shown that seasonal BP levels do not differ in the compared groups, except for winter indicators: winter daytime systolic BP levels were higher in the main group (p=0.03). Seasonal fluctuations in BP were not detected in the control group, however, they were present in the patients of the main group: winter daytime levels of diastolic BP and average daily levels of diastolic BP and systolic BP were higher than summer ones, and winter daytime systolic BP values (p<0.05) and clinical diastolic BP (p=0.004) – higher than autumn levels. Seasonal quality of life indicators in the main group were worse than in the control group in all seasons. Significant seasonal dynamics of quality of life indicators in patients in two groups was not detected. The ACQ questionnaire showed that asthma control changed in different seasons in accordance with the ACQ total score: in winter and spring – uncontrolled bronchial asthma (total score >1.5), in summer and autumn – partially controlled (total score ≤1.5). During the analysis of various factors associated with the combined primary endpoint (death, transient ischemic attack, angina pectoris, cardiac arrhythmias, arterial revascularization), relationships with quality of life indicators were revealed: negative connections – with indicators characterizing positive psychological health, mood at visit, positive correlations – with psychological abilities.

Conclusion: Seasonal fluctuations in ambulatory BP levels were not found in the control group and were found in the main group. The quality of life indicators for patients of the main group were significantly worse than in the control group for all components in all seasons. The control of asthma changed in different seasons in accordance with the ACQ total score: uncontrolled bronchial asthma occurred in winter and spring, partially controlled – in summer and autumn. Correlations of the combined primary endpoint with quality of life indicators were found after analyzing various factors.

840-846 71
Abstract

Aim. To study the effect of proton pump inhibitors (PPIs) on the development of hypomagnesemia in patients with paroxysmal atrial fibrillation (AF) on the background of autonomic sinus node dysfunction (ASND).

Material and methods. A prospective cohort study included 32 patients with an established diagnosis of ASND and often recurrent paroxysmal AF. The main group consisted of 17 patients who took pantoprazole at a dose of 20 mg 2 times a day as treatment of diagnosed duodenal erosions within 6 weeks from the time of the initial visit to an arrhythmologist. The remaining 15 patients did not take PPIs and were included in the control group. The determination of magnesium in whole blood, plasma and formed elements was carried out twice in all patients – at the initial visit and after 6 weeks. In addition, in the experiment, complex-forming activity of solutions of various PPIs (esomeprazole, pantoprazole, rabeprazole and omeprazole) with respect to magnesium ions was studied. The author’s method was used, based on turbidimitric determination of the light transmission during the heterogeneous reaction of the formation of magnesium phosphates in the presence of the analyzed drug or without it.

Results. There were no significant differences in the magnesium content in the blood of patients of the main and control groups before taking PPIs. After taking of pantoprazole by the patients of the main group there were significant differences between main and control groups in magnesium in whole blood (0.48 [0.44-0.51] mmol/l vs 0.55 [0.5-0.61] mmol/l, p=0.01) and its values in formed elements (0.52 [0.45-0.67] mmol/l vs 0.75 [0.65-1.2] mmol/l, p=0.009). Analysis of magnesium content in patients of the main group before and after taking of pantoprazole also showed a significant decrease in intracellular concentrations of the element (0.6 [0.51-1.0] mmol/l vs 0.52 [0.45-0.67] mmol/l, p=0.002), as well as decrease in its total content in whole blood (0.51 [0.45-0.59] mmol/l vs 0.48 [0.44-0.51] mmol/l, p=0.04). To substantiate the observed effects it was experimentally proved the possibility of formation of strong complex compounds between the ions of magnesium and PPIs: the highest activity was demonstrated by rabeprazole and pantoprazole (coefficients of complex formation per unit of total organic carbon – 1.5 and 0.72, respectively) and the lowest – omeprazole and esomeprazole (0.04 and 0.09, respectively).

Conclusion. A decrease of magnesium content in whole blood and formed elements in patients with paroxysmal AF on the background of ADSN was mediated by a six-week intake of pantoprazole in a dose of 20 mg 2 times a day for the treatment of concomitant erosion of the duodenum. When choosing PPIs for arrhythmological patients with concomitant gastro-duodenal pathology, it is advisable to be guided by the complexing activity of drugs with respect to magnesium ions: the most pronounced metal-ligand interaction with magnesium was shown by rabeprazole and pantoprazole, and the least – omeprazole and esomeprazole.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

847-853 54
Abstract

Aim. To estimate outcomes and risk of all-cause mortality, cardiovascular (CV) mortality, and non-fatal CV events in patients with a history of acute cerebrovascular accident (ACVA) according to data of outpatient prospective registries.

Material and methods. 986 patients with a history of ACVA (aged 70.6Ѓ}10.9 years; 56.8% women) were enrolled into the outpatient registry REGION-Ryazan, including the registry of patients with ACVA of any remoteness (ACVA-AR) – 511 (aged 70.4Ѓ}10.5 years; 58.5% women) and the registry of patients, visited outpatient clinics for the first time after ACVA (ACVA-FT) – 475 (aged 70.8Ѓ}11.3 years; 54.9% women). Outcomes, risk of all-cause and CV mortality, composite CV endpoint (CV death, nonfatal myocardial infarction and ACVA), hospitalizations due to CV diseases (CVD) were evaluated during 37 (17;52) months of follow-up period.

Results. 310 (31.2%) patients died during the follow-up. The most part of fatal outcomes (56.4%) was registered during the first year of follow-up, especially during the first 3 months (33.9%). Mortality among men (35.9%) was higher than among women (28.0%), р=0.008. 147 (28.8%) and 163 (34.3%) patients died in registries ACVA-AR and ACVA-FT, respectively (70.4% and 90.2% of fatal outcomes were from CV causes, respectively; р=0.04). The higher risk of death was associated with the following factors: age – hazard ratio (HR) 1.10 for each next year of age (95% confidence interval [95%CI] 1.09-1.12); sex (men) – HR 2.01 (95%CI 1.55-2.62); atrial fibrillation (AF) – HR 1.42 (95%CI 1,09-1,86); recurrent ACVA – HR 1.64 (95%CI 1.23-2.19); history of myocardial infarction (MI) – HR 1.45 (95%CI 1.09-1.93); low blood hemoglobin level – HR 2.44 (95%CI 1.59-3.79); heart rate ≥80 beats/min – HR 1.51 (95%CI 1.13-2.03); diabetes – HR 1.56 (95%CI 1.16-2.08); chronic obstructive pulmonary disease (COPD) – HR 1.89 (95%CI 1.34-2.66); no antihypertensive therapy in arterial hypertension – HR 2.03 (95%CI 1.42-2.88). The lower risk of death was associated with the following factors: prescription of ACE inhibitors (ACEI) – HR 0.60 (95%CI 0.42-0.85); angiotensin II receptor blockers (ARB) – HR 0.26 (95%CI 0.13-0.50), beta-blockers – HR 0.71 (95%CI 0.50-0.99); statins – HR 0.59 (95%CI 0.42-0.82). Factors, listed above, had significant association not only with all-cause mortality but also with CV mortality and composite CV endpoint. The higher rate of hospitalizations due to CVD was associated with younger age (incidence rate ratio [IRR] for 1 year 1.03; 95%CI 1.02-1.05; р<0.001), female sex (IRR 2.40; 95%CI 1.79-3.23; р<0.001), COPD (IRR 2.44; 95%CI 1.63-3.65; р<0.001) and heart rate ≥80 beats/min (IRR 1.51; 95%CI 1.12-2.04; р=0.007).

Conclusions. All-cause mortality in patients with a history of ACVA, enrolled in outpatient registry REGION, was 31.2% during 3-year follow-up. The proportion of CV death among the fatal cases was higher in the ACVA-FT registry than in ACVA-AR registry. The higher mortality rate was associated with the following factors: age, sex (male), recurrent ACVA, history of MI, diagnosis of AF, COPD and diabetes, low blood hemoglobin level, heart rate ≥80 beats/min, no antihypertensive therapy in arterial hypertension. The higher incidence of hospitalizations due to CVD was associated with younger age, sex (female), COPD and heart rate ≥80 beats/min. Prescription of ACEI, ARB, beta-blockers and statins was associated with lower risk of death and composite CV endpoint.

854-863 55
Abstract

Aim. To evaluate the association of Family History (FH) of cardiovascular diseases (CVD) in boys aged 12-13 years with the development of structural and functional changes in the left ventricle and stiffness of the main arteries in adulthood (43-46 years old) according to prospective study.

Material and methods. For the initial examination, boys were selected whose parents suffered from CVD at a young age or died prematurely from them (risk group). The comparison group was formed from a population sample of boys of a similar age without FH of CVD. The examination included a survey on a standard questionnaire, measurement of anthropometric indicators, blood pressure (BP), pulse counting, determination of the blood lipid spectrum. The intima-media complex thickness (IMT) of the common carotid arteries was measured; echocardiography and applanation tonometry were performed.

Results. The group with FH of CVD significantly (p<0.05) differed in childhood in terms of the body mass index (BMI) (18.8 vs 17.6 kg/m2), systolic BP (SBP) (117 vs 107 mm Hg), diastolic BP (DBP) (67 vs 56 mm Hg), average BP (81.8 vs 72.7 mm Hg) and triglycerides (0.79 vs 0.58 mmol/L). In adulthood, increased total cholesterol (TC) level (6.3 vs 5.8 mmol/L; p=0.036) and other indicators of atherogenesis were revealed in the risk group. The risk of fatal outcomes from CVD in the next 10 years in men with a family history of CVD in childhood was significantly higher compared to the control group (1.94 vs. 1.28; p <0.001). The main contribution to the total risk of fatal CVD in middle-aged men was made by TC and smoking. In the group with FH of CVD, higher stiffness of the arteries in adulthood was observed. There were found significant (p=0.002) intergroup differences in the IMT (0.73 vs 0.63 mm). A statistically significant positive relationship between BMI and some structural and functional indicators of the left ventricle and stiffness indicators of the main arteries was revealed. DBP and mean BP in childhood are associated with arterial stiffness in adulthood according to the parameters of central SBP and central DBP. BMI in boys is the most significant predictor for most structural and functional indicators of LV myocardial hypertrophy, in particular, LV myocardial mass (private R2=0.140) and interventricular septum thickness (R2=0.164; p=0.001), and arterial stiffness by central DBP parameter (R2=0.043; p=0.024) in adulthood. The risk of increased IMT development in males in adulthood with FH of CVD is 6.1 times higher than that of their peers without FH.

Conclusion. FH of CVD revealed in childhood in males is a risk factor for the development of early atherosclerosis and, due to its ease of detection, can be used as one of the criteria for the formation of high-risk groups for the purpose of primary prevention.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

864-872 101
Abstract

Aim. To study adherence to treatment with new oral anticoagulants (NOAC) and factors associated with it in patients with non-valvular atrial fibrillation (AF) within the outpatient PROFILE registry.

Material and methods. ANTEY study included 201 patients with AF from the PROFILE registry (89.3%): 118 males (58.7%) and 83 females (41.3%), aged 71.1Ѓ}8.7 years. The study consisted of two visits half a year apart (V0, V1) and a phone contact (PC) one year after V0. During V0 all patients were recommended to start therapy with one of the NOACs. Adherence to therapy was assessed during all visits with the use of the original questionnaire – National society of evidence-based pharmacotherapy (NSEPh) adherence scale, 8-item Morisky Medical Adherence Scale (MMAS-8) and direct doctors’ questioning.

Results. During V0 111 (55.2%) patients were recommended the use of rivaroxaban; 47 (23.4%) – the use of dabigatran and 43 (21.4%) – the use of apixaban. During V1 based on the results of the NSEPh adherence scale 155 (77.5%) patients were completely adherent (strictly followed doctors’ recommendations), 5 patients were partially adherent (violated doctors’ recommendations), 7 patients were partially non-adherent (stopped taking NOACs), and 33 patients were completely non-adherent (did not start taking NOACs). Out of 197 patients who completed MMAS-8 questionnaire 157 (79.7%) patients were partially adherent to treatment and 40 (20.3%) patients were non-adherent. None of the patients were completely adherent to treatment. According to doctors’ questioning, by the time of the PC 15 patients had not started taking the recommended NOAC – were completely non-adherent (CNA). According to the NSEPh adherence scale, by the time of the PC out of 197 patients (4 patients died) 158 patients were completely adherent to treatment, 6 – partially adherent, 18 – partially non-adherent and 15 – CNA. According to MMAS-8, by the time of the PC 153 (77.7%) patients were partially adherent to treatment, and 44 (22.3%) patients – non-adherent (none of the patients were completely adherent). Out of 15 CNA patients MMAS-8 revealed only 4 (27,6%) during B1, and 6 (40%) during the PC. NSEPh adherence scale revealed all CNA patients. The main reason for refusing to start NOAC therapy was their high price. Recently started use of NOACs was stopped mostly due to adverse effects of therapy (bleeding). The most common factors increasing patients’ adherence to NOACs were previous experience of taking this group of drugs and no history of any adverse effects during therapy.

Conclusion. The ANTEY study showed relatively high adherence to NOACs prescribed by doctors of the specialized cardiology department of the scientific center. The most common factors associated with early non-adherence to the new drug were high price and adverse effects of therapy, the latter influenced prolonged adherence as well. Previous experience of taking this group of drugs and no history of any adverse effects during therapy increased adherence to NOACs.

POINT OF VIEW

873-880 67
Abstract

Resources and methods for improving the prognosis in patients with chronic ischemic heart disease (IHD) are presented in the review. Information on the classes of drugs that improve the prognosis, and target values of the main physiological parameters that should be monitored during the treatment of patients with chronic IHD are also presented. The main attention is paid to antiplatelet agents and anticoagulants. The results of the most significant randomized clinical trials of the efficacy and safety of drugs from these classes in the treatment of chronic IHD are discussed. The results of the COMPASS study, which obtained confirmation of the positive effect of combined therapy with rivaroxaban and acetylsalicylic acid on the prognosis of patients with chronic IHD or peripheral artery disease, are presented in detail. The safety aspects of this therapy are discussed. The position of rivaroxaban in the treatment of patients with chronic IHD with sinus rhythm is presented according to the Recommendations of the European Society of Cardiology for the diagnosis and treatment of chronic IHD (2019).

881-891 106
Abstract

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is diagnosed in the absence of anatomically significant stenoses (<50% of lumen diameter) on coronary angiography and characterized by heterogeneity of etiologic factors. Recently, the mechanisms of MINOCA as well as the performance of diagnostic algorithms and therapeutic strategies have been extensively studied. The purpose of this review is to reflect the current concepts regarding the etiology and pathogenesis of MINOCA, diagnostic work-up methods and individualized treatment approaches. The article covers contemporary epidemiologic data, demographic and clinical patients’ characteristics and principal causes of MINOCA. We discuss aspects of disease definition and classification of related conditions involving troponin increase in the presence of normal coronary arteries. The importance of management strategy personalization for individual patients is stressed alongside stratification of risks of recurrent cardiovascular events. This review reflects key points from international consensus statements published by leading experts and suggests promising directions for future research.

892-899 79
Abstract

The prevalence of coronary heart disease (CHD) and type 2 diabetes mellitus (type 2 diabetes) in Russia and in the world continues to increase. Despite the prevention and optimization of therapy, CHD retains its leadership among all causes of death, and the mortality rate from type 2 diabetes and its complications gradually increases too. To improve the treatment of the above mentioned diseases, it is necessary to clarify the pathogenetic mechanisms of their development. The formation of endothelial dysfunction, characterized by an increase in the level of cell adhesion molecules and vasoconstriction, is a common link characteristic for the course and progression of CHD and type 2 diabetes. This article presents an analysis of preand clinical studies on the role of endothelial dysfunction markers: cell adhesion molecules (E-selectin), vasoconstriction (endothelin-1) and von Willebrand factor in patients with CHD, including those with type 2 diabetes mellitus.

900-905 64
Abstract

Currently, there are methods of drug exposure to the infection caused by the human immunodeficiency viruses (HIV), that allow to suppress the active replication of the virus in the patient's body. The era of antiretroviral therapy, which has allowed HIV-infected people to live longer, has begun. This led to an increase in their cardiovascular diseases, which occur at an earlier age and are more severe than in people without HIV. Specific or “nontraditional” risk factors damaging vascular wall occur in HIV patients along with traditional risk factors. These factors include: the negative impact of HIV on endothelium, an imbalance of inflammatory mediators, pathological immune activation, a decrease in the level of CD4 cells, a change in the number and function of platelets. The question of the effect of antiretroviral therapy on the occurrence of atherosclerotic vascular lesions remains debatable. Acute coronary syndrome (ACS) is one of the most frequent and most severe cardiovascular events in HIV-infected patients. The risk of myocardial infarction is highest in patients with a viral load of HIV-1 ribonucleic acid (RNA)≥500 copies/ml and a CD4 cell count of <200/ml. The most common form of ACS in HIV patients is ACS with ST segment elevation. Treatment of ACS in HIV patients has some difficulties: a high frequency of stent thrombosis, the frequent occurrence of thrombocytopenia, drug interactions with antiretroviral therapy. The high risk of developing cardiovascular diseases in HIV patients necessitates the introduction of active measures of primary and secondary prevention, taking into account the specific interaction of all drugs taken by the patient.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

906-917 125
Abstract

Nowadays, the modern approach to antihypertensive therapy is to prescribe in the most hypertensive patients fixed-dose combinations of antihypertensive drugs as initial therapy. This concept is reflected in the latest revisions of European and Russian guidelines for the management of arterial hypertension (AH). Above mentioned principle is referred as “single-pill combination” strategy and is given high priority in clinical practice with a high evidence level. According to this approach, one of the possible first line single-pill combinations is the combination of an angiotensin II receptor blocker and a calcium channel blocker. In both classes, the reference and the best representatives include, respectively, telmisartan and amlodipine, as a result of broad experience in their practical application and, most importantly, extensive body of evidence regarding to its effectiveness and safety. Both antihypertensive drugs are distinguished by an extra-longstanding antihypertensive effect that exceeds such one of other representatives in their classes, thereby a stable blood pressure control throughout the day is realized, and most importantly, in the early morning hours, that are the most dangerous in terms of adverse cardiovascular and cerebrovascular events. Another important telmisartan and amlodipine characteristics is their targetorgan protective properties, which is realized at all the levels. In addition, telmisartan has a unique ability to activate PPAR-у-receptors and improves the carbohydrate metabolism and lipid profile, which is advantageous in patients with concomitant metabolic syndrome and diabetes mellitus. The telmisartan and amlodipine features and their proven ability to improve prognosis in hypertensive patients served as background for creating a singlepill combination of these antihypertensive drugs, which fully meet with the requirements of current clinical guidelines for AH management and in which these drugs synergistically coupling resulting in more effective blood pressure control, increases the reliability of target-organ protection, and also improves the therapy safety profile.

918-927 61
Abstract

Recently, there has been a positive trend to reduce mortality from myocardial infarction. One of the reasons for such dynamics is the development of angiographic service in our country and the increase in the number of primary percutaneous coronary interventions. One of the most serious complications of endovascular interventions affecting the prognosis is the development of the phenomenon of slow or unrecoverable blood flow (≪slow/no-reflow≫ phenomenon). The reason for the development of this phenomenon is associated, first of all, with distal embolization by thrombotic masses and fragments of atherosclerotic plaque. In order to prevent this complication, manual thromboextraction was developed – the aspiration of thrombotic masses from the infarct-related artery. The manual thrombus aspiration has not been proven effective in a number of large randomized trials. In addition to the lack of influence on the prognosis, the method of manual thrombus aspiration significantly more often led to the development of ischemic strokes and currently should not be routinely carried out. Another method of preventing the phenomenon of delayed or unrecoverable blood flow is the use of glycoprotein IIb/IIIa receptor inhibitors which is, in contrast to the instrumental method, effective and relatively safe. According to a number of large randomized trials, drug treatment of this complication influences life expectancy in patients with ST-elevation myocardial infarction. At a time when there is already a meta-analysis on the routine use of glycoprotein IIb/IIIa receptor inhibitors during primary percutaneous coronary intervention and their positive impact on survival, in our country, unfortunately, the importance of these drugs is underestimated and according to the register they are used only in 3% of patients with ST-segment elevation myocardial infarction. This review presents studies and comparisons of glycoprotein IIb/IIIa receptor inhibitors existing on the market.

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2020-02-14

XXVII RUSSIAN NATIONAL CONGRESS “MAN AND MEDICINE”

Moscow, April 6-9, 2020
World Trade Center, 12 Krasnopresnenskaya embankment

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Oxana Drapkina, Head Freelance Specialist-Therapist, Ministry of Health of Russia, about the “Man and Medicine” Congress, Primary Care Development and Disease Prevention

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