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Rational Pharmacotherapy in Cardiology

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Vol 16, No 3 (2020)
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ORIGINAL STUDIES

342-347 81
Abstract

Background. The effect of stent size and number on left ventricular systolic function improvement after percutaneous coronary intervention (PCI) using drug eluting stent is not clear enough.

Aim. To study short-term effect of stent size and number on left ventricular systolic function improvement after elective PCI.

Material and methods. The study included 150 adult patients with electively stented left anterior descending artery lesion with drug-eluting stent. Patients were examined before PCI and 1 and 3 months after PCI using speckle tracking echocardiography.

Results. Before revascularization, mean left ventricular ejection fraction was 51.2%±5.7, mean global longitudinal peak systolic strain (GLPSS) --9.29±0.94%. One month after PCI, mean GLPSS improved significantly to -14.05±1.72% (p<0.001), 3 months after PCI, even more significant improvement in the GLPSS up to -18.61±3.02% (p<0.001) was recorded. After 3 months, 53 patients (35.3%) showed recovery to normal GLPSS. The predictors of non-improvement of GLPSS after 3 months were: diabetes mellitus (p=0.007), smoking (p=0.01), dyslipidemia (p=0.001), stent length (p=0.001), and a number of stents (p=0.04). There was strong negative correlation between stent length and improvement of the GLPSS in 1 month (p=0.007) and in 3 months (p<0.001). Also there was strong negative correlation between number of stents and improvement in 1 month (p=0.002) and in 3 months (p=0.004), but the correlation between stent diameter and improvement of the GLPSS was significant neither in 1 month nor in 3 months (p=0.924 and p=0.435, respectively).

Conclusion. Number and length of stents implanted were predictors to improvement of systolic function, while stent diameter doesn't affect left ventricular recovery.

348-355 76
Abstract

Aim. To compare the kinetics of dissolution (in vitro) and some pharmacodynamic and pharmacokinetic parameters of branded generic preparations of acetylsalicylic acid (ASA) in buffered form in cardioprotective doses [ASA 75 mg+Mg(OH)2 15.2 mg], which differ in the composition of excipients, with a reference drug.

Material and methods. Patients with cardiovascular diseases who had indications for ASA monotherapy (n=75) were included in a one-center open postregistration comparative non-randomized study. Patients were divided into 3 groups for treatment with one of the three studied drugs: Cardiomagnyl® (comparison drug; group 1; n=25), Trombital® (group 2; n=25) and Fazostabil® (group 3; n=25). A study of the kinetics of dissolution of the studied drugs in vitro under conditions of pH 1.2 has been performed. Also, platelet aggregation in response to arachidonic acid, the concentration of salicylic acid and the level of serum thromboxane B2 were studied in the compared groups.

Results. The average release profile of ASA by the 30th minute from Cardiomagnyl® was higher than for Trombital® and Fazostabil® (95.7%, 84.8%, 76.5% respectively). The similarity factor (f2) of ASA release for Trombital® was 39.3, and for Fazostabil® - 34.2. An index of f2<50 indicates a nonequivalent release of ASA compared with the reference drug. The serum level of salicylic acid 2 hours after taking the first dose of the drug in patients of group 1 was 2657.3±648.4 ng/ml, in group 2 - 2637.0±740.0 ng/ml (p=0.03) and in group 3 it was to 2632.1±666.0 ng/ml (p=0.002). The platelet aggregation after 3 days decreased and in groups 1, 2 and 3 were respectively 7.6%, 32.2% (p=0.000) and 16.3% (p=0.009). Differences in the disaggregation effect between the groups persisted by the 7th day of the study (7.9%, 9.1% and 20.5% respectively; p=0.04 for the latter). The thromboxane B2 level by the 3rd day of administration decreased compared to the initial level in group 1 to 15.5%, in group 2 to 21.1% and in group 3 to 20.0% (p=0.05 for both). The trend persisted by the 7th day.

Conclusion. The pharmacodynamic and pharmacokinetic parameters of the studied drugs differed statistically significantly with the advantage for the comparison drug despite the same active substance.

356-362 82
Abstract

Aim. To study the possibilities of photoplethysmography (PPG) in evaluation of arterial stiffness, arterial age and early vascular aging (EVA) in healthy individuals and patients with cardiovascular risk factors.

Material and methods. The material of the study was the data from a survey of large teams undergoing medical examination in a group of clinics of Medical Center “SOGAZ”. A total of 783 men aged from 20 to 92 years were examined. The mean age was 48.2±10.32 years. PPG was used as a special research method, performed using the AngioScan-01 diagnostic complex. The following indicators were evaluated: stiffness index (SI), reflection index (RI), augmentation index (Alp75), age index (AGI) and pulse wave types (PV-type). For determining the vascular age (VA), correlation field of the dependence of AGI on the age of the subject was built, and then the VA was calculated by the value of the AGI.

Results. The greatest correlation with passport age was revealed for the AGI indicator (r=0.54) at the first stage of the study. EVA-syndrome criteria were considered as values of the AGI, beyond the 90th percentile (n=65), and the criteria for “young vascular age” (n=87) were AGI values below 10 percentile with age correction. Comparison of these two alternative subgroups (in men aged from 40 to 59) in terms of arterial stiffness showed significant differences in SI (8.2±0.99 vs 7.6±0.89, respectively, p=0.001), Alp75 (-0.2±14.54 vs 20.5±10.31, respectively, p=0.0001), PV-type. The frequency of detection of multiple risk factors according to the results of questionnaires and laboratory diagnostics in patients with EVA-syndrome was also significantly higher. Assessment of the contribution of vascular risk factors to vascular aging showed that the leading positions are occupied by hypertension, hypertriglyceridemia, abdominal obesity, hyperglycemia, and smoking.

Conclusion. PPG is a simple, fast, and informative method that allows to evaluate the parameters of the vascular wall stiffness. It can be assumed that its use in screening examinations of middle-aged men can help in identifying patients requiring observation and intensive prevention.

363-369 72
Abstract

Background. Despite the progress in the diagnostics of microvascular angina (МА) there is no effective pathogenetic therapy.

Aim. To study the effect of trimetazidine and sulodexide as a part of drug therapy on clinical manifestations, exercise tolerance, quality of life, myocardial perfusion and endothelial function in patients with MA.

Material and methods. Patients with MA (n=90) were included into the study and randomized into 3 groups. Patients of the first group (control; n=30) received standard antianginal therapy. The second group (treatment group; n=30) received standard therapy and sulodexide (1 ampoule of 600 IU intramuscularly for 10 days, then 1 capsule of 250 IU, 2 times a day). Patients of the third group (treatment group; n=30) received standard therapy and trimetazidine with modified release 35 mg 2 times a day. Evaluation of angina symptoms and quality of life by the Seattle Questionnaire, stress (treadmill) test, positron emission tomography (baseline, adenosine test, cold-pressor test), peripheral arterial tonometry were performed at baseline and 3 months after starting treatment.

Results. After 3 months of treatment a significant improvement in symptoms, quality of life and results of stress-test were observed only among patients of treatment groups, most pronounced in the 3rd group. Patients of this group showed an increase in myocardial blood flow >25% according to positron emission tomography (from 86.2±29.7 to 129.5±41.0 ml/100g/min, p<0.05 for anterior interventricular artery; from 93.3±30.5 to 131.7±32.7 ml/100g/min, p<0.05 for circumflex artery; from 91.3±30.4 to 135.9±41.1 ml/100g/min, p<0.05 for right coronary artery) and a significant increase in coronary reserve, as well as an improvement in endothelial function: an increase in coronary reserve of endothelium-dependent vasodilation, an increase in the reactive hyperemia index according to peripheral arterial tonometry (from 1.44±0.14 to 1.73±0.18, p<0.001).

Conclusion. Improvement of the clinical picture, quality of life, myocardial perfusion, and endothelial function was observed among microvascular angina patients who were treated with standard antianginal therapy and trimetazidine.

370-376 68
Abstract

Aim. To identify genetic predictors of diastolic dysfunction and signs of endothelial dysfunction in relation to indicators of left ventricular myocardial deformity in patients with hypertension.

Material and methods. The study included 74 patients (38 women and 36 men) with hypertension 1-2 stages observed in the cardiology department of the Road clinical hospital at Chita II station. The mean age of patients was 32±9.4 years. Circulating endothelial cells (CEC) were determined by flow cytometry with BT 5000 device and antibodies to CD146+, CD45. Besides, 7AAD ion dye was used to detect living and dead endothelial cells. The number of CD146+, CD45 cells per 500000 blood cells was determined. Changes in CEC, Living/Dead CEC were studied. The data was processed using CXP Cytometer and Kaluza programs. The standard echocardiography, Doppler echocardiography and tissue Doppler echocardiography were used. Frequency distribution of alleles and genotypes: 1 mutation nitric oxide synthase 3 gene NOS3 -786 T>C; (С-786Т) in relation to indicators of left ventricular myocardial deformity was analyzed in hypertensive patients with or without diastolic dysfunction as well as in the control group. Polymerase chain reaction with detection of amplification product in real time (RCR-rt) or electrophoresis in agarose gel on genomic DNA of peripheral blood leukocytes were used for studying gene mutations.

Results. Development of diastolic dysfunction in hypertensive patients enhanced with the carrier of the genotype NOS3 -786 CC (р=0.01 2, x2=1 2.53), endothelial dysfunction was manifested by an increase in the number of circulating endotheliocytes and was associated with a decrease in global longitudinal deformation of the left ventricle.

Conclusion. Endothelial dysfunction in patients with hypertension is associated with a violation of global longitudinal deformation; and in patients with diastolic dysfunction these abnormalities are more pronounced than in patients without diastolic dysfunction.

377-382 83
Abstract

Aim. To assess the effect of combination therapy (perindopril, indapamide, amlodipine) on vascular stiffness and endothelial function in patients with heart failure with preserved ejection fraction (HFpEF).

Material and methods. Patients with HFpEF (n=30) were included in a nonrandomized, uncontrolled trial. All patients had a comprehensive examination: a six-minute walk test to determine exercise tolerance, echocardiography, determination of the diameter of the brachial artery with an assessment of its endothelium-dependent vasodilation (EDVD). Photoplethysmography and compression oscillometry were also carried out to assess the stiffness characteristics of vessels of various calibers and the determination of the cardio-ankle vascular index. Patients were examined initially and 16 weeks after the combination therapy order (perindopril 10 mg/day, indapamide 2.5 mg/day, amlodipine 5 mg/day).

Results. The data obtained during therapy shows improvement of the endothelial function for all patients: the initial EDVD was 8.5%, by the end of the observation period it increased to 11.4% (p=0.007). A significant decrease in the systemic vascular resistance from 2591 dyn*cm-5 to 2380 dyn*cm-5 (p=0.03) and in the level of specific peripheral resistance from 32.9 dyn/sec/cm-5 to 28.5 dyn/sec/cm-5 (p=0.0051). The stiffness indices of small resistive vessels also decreased: vascular stiffness index from 10.2±2.2 m/sec to 8.4±2.5 m/sec (p<0.0001) and pulse wave reflection index from 70.2±13.5% to 61.9±14.7% (p=0.0011). Cardio-ankle vascular index (CAVI) initially amounted to 9.2±1.3 and decreased by the end of the observation period during treatment to 8.3±1.1 (p=0.0003). The pulse blood pressure was significantly decrease from 71.31±15.5 mm Hg to 64.5±12.9 mm Hg (p=0.0048) and there was a tendency to decrease in pulse wave velocity from 808 cm/sec to 730 cm/sec.

Conclusion. The results of the study showed a statistically significant improvement in the elastic component of small resistive and major vessels, the endothelial function. The obtained results prove a decrease in the stiffness characteristics of blood vessels during the combination therapy.

This suggests that the combination of drugs with a different mechanism of action improves not only the state of the endothelium and its function, but also significantly reduces the stiffness of the great vessels, restores the microcirculatory support of the interstitium of the myocardium and vascular wall in patients with HFpEF and leads to an improvement in the clinical status of patients with this syndrome.

NOTES FROM PRACTICE

383-391 63
Abstract

Left ventricular non-compaction (LVNC) is a genetically determined cardiomyopathy characterized by different variants of the clinical course. LVNC family cases allow to study in more details the role of genetic factors in cardiomyopathy pathogenesis and prognosis, as well as to determine clinical course features.

Aim. To demonstrate a case of LVNC familial form with a stable benign course and to assess the possible relationship of the detected mutation with the disease prognosis.

Material and methods. A family with LVNC was included in the study. The patient with LVNC and his 1st and 2nd degree of kinship relatives underwent clinical and instrumental examination and exome sequencing. LVNC was diagnosed in proband and proband's father. LVNC diagnosis was established basing on echo and magnetic resonance imaging (MRI) criteria.

Results. This article presents the results of a comprehensive clinical and instrumental examination of a family with LVNC with a new variant in the MYH7 gene, the absence of intramyocardial fibrosis according to MRI of the heart and a favorable disease course, both in proband's father and proband himself. A comparative analysis of the data obtained with the results of recent large-scale studies and meta-analyses devoted to the study of prognostic factors in patients with LVNC, with identified variants in the MYH7 gene.

Conclusions. The variant of p.His1338Pro identified in the MYH7 gene may be associated with the development of LVNC with a benign course.

392-398 59
Abstract

Whipple's disease is caused by Tropheryma whipplei and is known to have protean clinical presentation which could be influenced by patient's immunologic and genetic features. In contemporary literature abundant amount of data could be found on extensive prevalence of infectious endocarditis caused by Tropheryma whipplei. This article presents history of a patient who was observed because of ischemic heart disease, angina pectoris, myocardial infarction, possible ischemic cardiomyopathy and in whom infectious endocarditis complicated by severe aortic regurgitation needing aortic valve replacement surgery was eventually diagnosed. Our patient did not meet Duke criteria, which is a sign of infectious endocarditis caused by Tropheryma whipplei, but a thorough analysis of the disease course, clinical features, heart ultrasound and clinical improvement on specific therapy against Tropheryma whipplei aroused our suspicion, and morphological and bacteriological analysis of the involved (excised) valve, confirmed the diagnosis of Whipple disease. The article presents differential diagnostic criteria of aortic insufficiency and possible causes of coronary insufficiency in the absence of marked coronary atherosclerosis.

399-403 71
Abstract

The article describes the clinical observation of thrombosis of prosthetic cardiac valve in a 51-year-old female patient, 9 years after surgical intervention for a degenerative aortic valve disease with the installation of mechanical prosthesis into the aortal position and further warfarin medication, with absence of international normalized ratio (INR) control over the past six months. The patient's condition worsened under the “mask” of decompensation of left ventricular circulatory failure; pulmonary embolism and acute coronary syndrome were also excluded. At the same time, the negative dynamics of the cardiac ultrasound data were underestimated: the appearance of prosthetic dysfunction, an increase in the degree of valve regurgitation, severe pulmonary hypertension, as well as anamnestic data (double acute cerebrovascular accident and lack of INR control for a long time, lability of its values during index hospitalization).This case can be important in terms of clarifying the reasons for the decompensation of chronic cardiac failure in patients with valvular defects and mechanical valve prosthetics, especially in cases of irregular INR monitoring or not being it in the target range, and progressive negative dynamics of the cardiac ultrasound data.

ASSOCIATED PROBLEMS OF CARDIOLOGY

404-414 83
Abstract

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

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

415-423 96
Abstract
The prevalence of hypertension in the Russian Federation (RF) has been growing in recent years, which causes significant socio-economic burden.
Aim. To evaluate economic burden of hypertension in the RF in 2016 including direct costs and economic losses caused by decreased labor efficiency.
Material and methods. The calculation included the prevalence of hypertension in the RF and the relative risk of hypertension for cardiovascular diseases (CVD) (including stroke and coronary heart disease), chronic obstructive pulmonary disease (COPD), type 2 diabetes mellitus (DM2), cancer of the trachea, bronchi and lungs, breast and prostate. The calculation included Russian statistics on noncommunicable diseases (NCD) for 2016. Statistical analysis – calculations were performed by Microsoft Excel 10.0
Results. Population attributable risk (PAR) of hypertension in mortality from all CVDs was 34%, in morbidity – 30%, including PAR in mortality from coronary heart disease and stroke 38% and 60%, respectively; the same in morbidity – 28% and 14%, respectively. For DM2 PAR in mortality was 1%, in morbidity – 18%. For COPD PAR in morbidity was ≈24%. PARs in morbidity and mortality for lung, bronchi and trachea cancer were ≈12%, for prostate cancer ≈3%, and for breast cancer 6%. Direct medical costs associated with the analyzed NCDs exceeded 84 billion rubles, direct non-medical costs – over 1.5 billion rubles. In the structure of economic burden, the main part was associated with gross domestic product (GDP) losses due to premature mortality due to hypertension.
Conclusion. The total economic burden associated with hypertension in 2016 amounted to 869936 million rubles that corresponded to 1% of Russian GDP.
424-431 57
Abstract

Aim. To evaluate the effectiveness of the survey method for detecting the probability of cardio-cerebral symptoms and diseases as an indicator of the quality of its use in the framework of medical examination.

Material and methods. An analysis of the results of automated survey of all people who passed medical examination in 2018 was carried out in the pilot Bryansk polyclinic in order to identify the likelihood of cardio-cerebral symptoms and anamnesis of coronary heart disease and cerebrovascular diseases.

Results. Clinical examination coverage in the pilot clinic was 87.0%. A total of 7588 people were surveyed and interviewed, 4980 women and 2608 men; the majority of those surveyed (69.7%) were under the age of 60 years. The probability of having angina according to the automated survey was found in 3.7% of patients, and in 2.5% it was detected for the first time, i.e. cases of early detection made up the majority (69.2%). The proportion of first-time symptoms was particularly high in young patients (91.2%), which is especially important from the point of view of timely prevention. Neurological symptoms according to the automated survey were detected in 11.7% of the examined patients, and in 10.8% they were detected for the first time, i.e. also in the majority of patients with these symptoms (92.4%). High detection of cardio-cerebral symptoms in young people without a previous history of coronary heart disease and cerebrovascular disease was demonstrated.

Conclusion. The clinical and organizational feasibility of the questionnaire method is shown in the framework of phase 1 of the clinical examination of the adult population performed in an automated questionnaire mode. This will eliminate the subjectivity in the interpretation of responses and provide an opportunity to use the survey data in the formation of target groups for additional tests that will surely improve the quality of medical examination and cardio vascular diseases prevention in outpatient medical care.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

432-438 55
Abstract

Aim. To study the long-term outcomes of patients who survived after acute myocardial infarction (AMI) in a prospective outpatient registry.

Material and methods. Patients (n=160) who applied to one of the outpatient clinics in Moscow after AMI were included in the registry PROFILE-MI. The total follow-up period was 1.5 years. The primary combined endpoint (PCE) included death from any cause, cardiovascular events (nonfatal myocardial infarction, nonfatal cerebral stroke), emergency hospitalizations for cardiovascular diseases, significant cardiac arrhythmias. 1-year observation period was taken in analysis of the factors affecting the development of PCE.

Results. During the observation period, 16 patients (10%) died. Life status was not obtained in 4 patients. Most of the deaths were due to cardiovascular complications; in a quarter of patients, repeated AMI was the cause of death. After 12 months of follow-up, the development of PCE was observed in 42 patients. PCE has been identified more often in elderly patients, in patients who had certain complications in the acute period of AMI, in patients who had swelling at the time of the examination in the outpatient clinic, who complained of shortness of breath, and also had a heart rate (HR) more than 70 min-1. Normal blood pressure (within 120/80-139/89 mm Hg) and HR at 60-70 min-1 had a positive prognostic influence.

Conclusion. Despite intensive treatment in a hospital and the relatively high quality of secondary pharmacological prevention, the prognosis of life and disease in patients after AMI remains quite serious.

INNOVATIVE CARDIOLOGY

439-448 110
Abstract
Chronic heart failure (CHF) is considered the leading cause of death in patients with established cardiovascular (CVD) and metabolic diseases. Although the current treatment strategy has improved survival and clinical outcomes, the prevalence of CHF shows an increase. Current clinical guidelines for the treatment and prevention of CVD note the role of biological markers as a fairly simple and powerful tool for diagnosing, stratifying risk and predicting CHF. However, it is unclear whether all of these biological markers are equally capable of predicting cardiovascular mortality and heart failure related outcomes in patients with acute and chronic heart failure, as well as in different phenotypes of heart failure. However, the results of numerous studies demonstrate scientific interest in the processes of angiogenesis among patients with CHF. There is an impressive body of evidence linking CHF to the level of markers such as vascular endothelial growth factor, pentraxin-3, and transforming growth factor beta. The review presents the data of domestic and foreign clinical studies devoted to the study of the level of angiogenesis markers among patients with CHF.

POINT OF VIEW

449-456 79
Abstract

The important result of the revision of the European and Russian guidelines for the management of arterial hypertension was a conclusion about the need to use a double combination of antihypertensive drugs as the first stage of antihypertensive therapy. The review presents benefits of combined antihypertensive therapy, confirmed by the results of randomized clinical trials and meta-analysis. There are literature data suggesting one of the first line reasonable combinations is the combination of angiotensin converting enzyme inhibitors (ACEI) and thiazide-like diuretic. The article discusses the benefits of single-pill combinations before free ones, such as increase in patient adherence to long-term treatment, reduction in the cost of the drug and the number of tablets. As an example, a highly effective single-pill combination of one of the most used ACEI, lisinopril and indapamide sustained release, is considered, which has protective activity, vasodilator properties and metabolic neutrality. The article presents the data of the PIFAGOR IV study that indapamide is the most widely used diuretic in Russia, which is characterized by high antihypertensive efficacy, good tolerance, cardioprotective, nephroprotective and osteoprotective properties. The results of large-scale studies, which show the ability of lisinopril to retain target blood pressure level, antiproteinuric and cardioprotective activity, are also presented. This single-pill combination has a long additive effect, contributing to reliable daily monitoring of blood pressure. The authors expressed the opinion that the prescription of highly effective single-pill combinations will contribute to organ protection and reduce the risk of cardiovascular complications development.

457-464 172
Abstract
Data on the effect of magnesium on the homeostasis of the body and on the cardiovascular system, are presented in the article. These data supplement information on studies of the role of magnesium in many body processes. The influence of lifestyle on magnesium metabolism, the pathological processes that cause its deficiency, and the clinical picture of hypomagnesemia are presented in the article. The necessary daily amount of magnesium, ways to restore the magnesium deficiency, both nutritional and with the help of magnesium-containing pharmacological preparations, their form, bioavailability and dosage regimen are discussed. Diseases that occur and/or worsen with hypomagnesemia are considered. Data on the iatrogenic effect of many drugs, including cardiological, removing magnesium from the body and ways to solve this issue, are also presented. Hypomagnesemia exacerbates the course of cardiovascular disease. Elimination of magnesium deficiency can contribute a lot to the prevention of morbidity and the optimization of treatment of patients.
465-473 73
Abstract

Patients with diagnosed coronary artery disease and/or peripheral arterial disease have a high risk of cardiovascular death and disabling vascular events, including stroke, myocardial infarction, and amputation. Secondary prevention in these high-risk patients should include control of modifiable risk factors for the progression of atherosclerosis and antithrombotic therapy to prevent atherothrombosis. Analysis of the literature from the databases PubMed, MEDLINE, HighWire Press was carried out to determine the modern possibilities of assessing the risk of ischemic and hemorrhagic events in a stable course of cardiovascular diseases caused by atherosclerosis, which can be used to determine the categories of patients with the greatest potential benefit from combination antithrombotic therapy. The results of a large randomized study COMPASS, their sub-analyses and the work of other authors, published over the last year, allow us to formulate reasonable conclusions that facilitate the adoption of medical decisions when choosing treatment tactics for patients with a stable course of atherosclerotic cardiovascular diseases. When using low doses of rivaroxaban and aspirin in high-risk groups, the rate of adverse events, including cardiovascular death, myocardial infarction, stroke, and vascular complications of peripheral artery disease, can be significantly reduced. High-risk criteria for severe cardiovascular complications are multifocal atherosclerotic lesions, heart failure, myocardial infarction, diabetes mellitus, or chronic kidney disease. Patients with the highest risk of vascular events will receive the greatest absolute benefit from this treatment. Secondary prevention in patients with chronic coronary syndromes, sinus rhythm and a moderate risk of cardiovascular complications using low doses of rivaroxaban and aspirin is justified, since the ratio of its risk and benefit remains favorable.

474-480 54
Abstract

In the new recommendations of the European Society of Cardiology for Chronic Coronary Syndrome, a new diagnostic algorithm is proposed in patients with suspected coronary artery disease (CAD). The purpose of this algorithm was to propose a solution of the accumulated problems in the diagnosis of CAD, in particular, a high frequency of negative non-invasive tests and unchanged coronary arteries during invasive coronary angiography. The new diagnostic algorithm includes a revision of the pre-test probability scale, the introduction of the concept of clinical probability, clarifies the role of various non-invasive tests with the central role of non-invasive testing for myocardial ischemia. However, due to the lack of data on a number of key issues, significant gaps remain that impede the use of this algorithm in practice. This review is devoted to the consideration of problematic issues of the proposed algorithm, while a critical analysis of the algorithm itself and an assessment of recent publications are carried out. Various aspects of the application of a new scale for assessing pre-test probability, determining the clinical probability of CAD, the choice of non-invasive and invasive diagnostic tests, the place of the load electrocardiography test in the diagnosis of coronary heart disease are examined in detail. Gaps in the evidence base and limitations of the algorithm are considered, as well as the possibility of its use in Russian conditions. This review can help in adapting new recommendations to domestic conditions, as well as help practitioners to use it in their daily work.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

481-486 92
Abstract

This review analyzes existing approaches to the treatment of COVID-19 patients with antimalarial drugs from the standpoint of rational pharmacotherapy. Particular attention is paid to drug interactions and side effects of co-administration of chloroquine/hydroxychloroquine and azithromycin, considering the problem of cardiotoxicity and the high likelihood of cardiovascular disease in middle-aged and elderly people with COVID-19. The article discusses the prospects of using another representative from the group of antimalarial drugs - mefloquine in the treatment of COVID-19. Special attention is paid to the “proarrhythmogenic” side effects of azithromycin therapy, as well as to the problem of resistance of microorganisms to macrolides during antibiotic therapy of pneumonia, in particular to azithromycin. In conclusion, the article discusses the possibilities of alternative methods in the treatment of this disease.

487-497 80
Abstract

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

498-502 50
Abstract

One of the trends in modern cardiology is the use of omega-3 polyunsaturated fatty acids (ω-3 PUFA) in the prevention of heart rhythm disorders and the prevention of sudden cardiac death. In experimental studies, it was found that ω-3 PUFAs have a variety of pleiotropic effects: they reduce the formation of oxygen radicals, reduce reperfusion complications, reduce the level of thromboxane and platelet aggregation, and improve endothelial function. The ability of ω-3 PUFA to have an anti-inflammatory effect, which includes the inhibition of leukocyte chemotaxis, the expression of adhesion molecules, the formation of eicosanoids and biologically active substances with powerful anti-inflammatory properties. One of the most significant effects of ω-3 PUFA can be considered their anti-atherogenic effect. Antiarrhythmic properties of го-3 PUFA are associated with the effect on the ion channels of cardiomyocytes, they are able to activate "slow" calcium channels, increase the activity of Ca2+/Mg2+-ATPase and reduce the work of sodium channels. In animal experiments, it has been shown that in conditions of ischemia or adrenergic stimulation, ω-3 PUFA stabilizes the cardiomyocyte membrane, can increase the duration of the effective refractory period, and prevent the development of various heart rhythm disorders. Clinical studies have shown that the administration of ω-3 PUFA in addition to standard treatment reduces the risk of new cases of atrial fibrillation, ventricular arrhythmias and sudden cardiac death.



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