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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 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 (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 16, No 4 (2020)
View or download the full issue PDF (Russian)

ORIGINAL STUDIES

508-515 73
Abstract

Aim. To evaluate the effectiveness of a comprehensive prehabilitation program including the optimization of drug therapy for patients undergoing elective coronary artery bypass grafting (CABG).

Material and methods. 56 male patients with stable angina referred to elective on-pump CABG were enrolled in a study. All patients were screened for eligibility according to the inclusion/exclusion criteria and then randomized into two groups. Group 1 patients (n=28) underwent preoperative management (prehabilitation) for 14 days, including patient education and physical rehabilitation. Trimetazidine in a dose of 80 mg per day was added to the standard drug therapy. Group 2 patients (n=28) underwent similar preoperative management, but with the standard drug therapy without trimetazidine. In addition to the routine methods of preoperative management, all patients underwent the 6-minute walk test (6MWT) to assess exercise tolerance and speckle tracking echocardiography to measure left ventricular (LV) longitudinal deformation. Serum troponin T was measured in all patients. The measurements were performed at admission and after the surgery.

Results. Patients did not differ in the main clinical and demographic data, as well as the main preoperative speckle tracking echocardiography findings. The intraoperative parameters were comparable in both groups. The rate of early postoperative complications was 61% (n=17) in Group 1 and 64% (n=18) in Group 2 (p>0.05). LV ejection fraction significantly decreased postoperatively in both groups (p<0.01) as well as LV longitudinal deformation as compared to the baseline. Patients receiving the standard therapy without trimetazidine reported a significant decrease in the longitudinal strain after CABG compared with the baseline (p=0.01). There were no statistically significant differences in most preoperative and postoperative indicators of longitudinal deformation among patients treated with trimetazidine. Postoperative values of GLPS-LAX and GLPS-Avg were significantly higher in the trimetazidine group than those in the control group (p=0.04). Group 1 patients reported longer distance covered in 6MWT than Group 2 patients while assessing exercise tolerance: 370.0 [260.0;415.0] vs 242.0 [202.0;350.0] m, respectively (p=0.0059).

Conclusion. The addition of trimetazidine in a dose of 80 mg daily in the prehabilitation program for patients undergoing elective CABG demonstrated better postoperative indicators of LV longitudinal deformation and an increase in exercise tolerance. Obtained findings allowed considering this approach to the preoperative management as an additional method of cardiac protection and optimization of the functional status of patients.

516-521 70
Abstract

Aim. To study changes in vascular wall stiffness in patients with obesity and paroxysmal atrial fibrillation (AF) during sinus rhythm retention.

Material and methods. The study included 86 obese patients aged 38 to 72 years. Patients were divided into 2 groups: 42 patients with paroxysmal AF and obesity (Group I) and 44 patients with obesity and without rhythm disturbance (Group II). All patients were evaluated for the main parameters of arterial wall stiffness: the heart-ankle vascular index (CAVI) and the ankle-brachial index (ABI) in the right and left main arteries.

Results. Body mass index (BMI) did not differ significantly between groups. The prevalence of visceral obesity in patients with paroxysmal AF was significantly higher than in patients without heart rhythm disorders. The study of vascular wall rigidity revealed a significant increase in the CAVI index in patients with paroxysmal AF compared with this in patients without cardiac arrhythmia. The average value of the CAVI index was 9.61±1.51 and 7.92±0.18, respectively (p=0.0003). In patients with obesity and paroxysmal AF, correlations were found between waist circumference to hip circumference (WC/HC) ratio and CAVI index (r=0.455, p=0.004); WC/height ratio and CAVI index (r=0.443, p=0.003); between WC and CAVI index (r=0.493, p=0.002). A positive direct relationship was found between CAVI index and the frequency of AF attacks during the year: r=0.782 (p=0.001).

Conclusion. A significant increase in the CAVI index, indicating a change in vascular wall stiffness, was found in patients with obesity and paroxysmal AF when compared with overweight patients without heart rhythm disorders. The increase in the CAVI index was correlated with the increase in WC, the WC/HC ratio, and WC/height ratio. There was a significant direct relationship between the CAVI index and the frequency of arrhythmia attacks in patients with obesity and paroxysmal AF.

522-527 70
Abstract

Coagulation status with vitamin K antagonists (VKAs) needs to be monitored carefully to ensure maximal efficacy with minimal complication rates.

Aim. To study the international normalized ratio (INR) values in patients on VKAs in selected area, find out which patient characteristics that is associated with good INR control and calculation of the time in the therapeutic range (TTR) according to the number of INR/Patient.

Material and methods. A total of 200 patients with non-valvular atrial fibrillation prescribed vitamin K antagonist as anticoagulant were evaluated. They were divided into two groups: group I with TTR≥65% (n=93) and group II with TTR<65% (n=107). Stroke and hemorrhagic risks were calculated by means of the CHA2DS2-VASc score and HAS-BLED score, respectively. Presence of comorbid diseases was assessed by the Charlson index. TTR was calculated using Rosendaal method.

Results. Patients in group I (TTR≥65%) were younger (p<0.001), more often men (p<0.074) with a high level of education (p<0.001), had lower stroke and hemorrhagic risks (mean CHA2DS2-VASc score was 1.0 and HAS-BLED score – 0.0), and also had fewer comorbidities (mean Charlson index was 0.0; p<0.001) compared to patients in group II (TTR<65%). The rate of inadequate control with VKAs (TTR<65) was 52%. Multivariate logistic regression analysis was done to see the significant independent predictors for a good INR control i.e. TTR≥65%. It was found that high level of education compared to lower levels is the only significant independent predictor for obtaining good INR control (odds ratio=133, 95% confidence interval 34.24-514.44, p<0.001).

Conclusion. It was found that high level of education compared to lower levels is the only significant independent predictor for obtaining good INR control.

528-535 109
Abstract

The high prevalence of lipid metabolism disorders in the Russian population and their contribution to cardiovascular risk require an optimization of their pharmacotherapy in clinical practice.

Aim. To study the possible benefits of statin therapy in fixed doses for primary and secondary prevention of cardiovascular disease in outpatient practice.

Material and methods. Ambulatory patients (n=300) with a high or very high risk with hypercholesterolemia who had indications for statin treatment for primary or secondary prevention of cardiovascular diseases were included into a non-randomized trial. Patients were 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. Laboratory studies included determination of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c). Changes in lipid levels, the frequency of reaching target TC and LDL-c levels were evaluated.

Results. Titration-free statins treatment (Group 2) allowed reaching the target levels of TC and LDL-c after 12 months in 73.9% and 56.3% of patients, respectively. Significant changes were found after 3 months visit. In Group 1, these indicators were slightly lower (56.8% and 53.4%, respectively), while significant changes in the LDL-c level were found later than in Group 2. More than 50% of patients taking statins for secondary prevention, reached the target level of TC and LDL-c. At the same time, when using titration-free statin therapy, such results were recorded after 3 months. Patients taking statins for primary prevention achieved the TC target level in 95.7% of cases (subgroup 2A). The frequency of reaching the LDL-c target level in the subgroups of primary prevention was slightly lower.

Conclusion. The use of a titration-free statin treatment regimen allowed to more effectively control of TC and LDL-c levels in patients with high and very high cardiovascular risk compared to the traditional statin therapy regimen, and to achieve target lipid levels earlier.

536-541 55
Abstract

Supraventricular arrhythmias, including atrial fibrillation (AF), are a current problem for patients in the older age group due to the possibility of lifethreatening complications. Elderly patients have pre-conditions for the development of supraventricular rhythm disturbances (age-related structural and functional changes in the myocardium, concomitant diseases).

Aim. To study the features of structural and functional changes in the myocardium of the left heart in elderly patients, depending on the presence of supraventricular arrhythmias.

Material and methods. The cross-sectional study included 200 individuals aged 60 to 89 years. All participants underwent echocardiographic examination and 24-hour electrocardiogram (ECG) monitoring. The patients of the study cohort were divided into 3 groups: group 1 consisted of patients with coronary heart disease (CHD) without heart rhythm disturbances (n=80); group 2 consisted of patients with CHD and paroxysmal AF (n=40); group 3 consisted of patients with CHD and supraventricular extrasystoles (n=40). The control group consisted of patients of the older age group without CHD and rhythm disturbances (n=40).

Results. In patients with paroxysmal AF and frequent supraventricular extrasystoles, large sizes of the left atrium were revealed (anteroposterior dimension: 4.30±0.07 and 4.12±0.12 cm; upper-lower: 6.15±0.03 and 5.96±0.10 cm; medial-lateral: 4.15±0.11 and 3.87±0.09 cm, respectively). In patients with CHD and rhythm disturbances, the presence of a combined increase in the size of the left atrium and a decrease in myocardial contractility was revealed (ejection fraction of the left atrium in groups 2 and 3 – 27.2±0.1% and 27.9±0.1%, respectively, vs 36.3±0.1% and 38.20±0.02%, respectively in group 1 and control). The duration of ischemic changes during 24-hour ECG monitoring was also greater in group 3 compared with groups 1 and 2 (249.6 vs 27.1 and 66.4 min, respectively). In groups 2 and 3, a discordant effect of the sympathetic and parasympathetic nervous systems on heart rate variability was revealed.

Conclusion. For elderly patients, morphological and functional changes are characteristic, which consist in the restructuring of the myocardium and changes in heart rate variability with a prevalence of the sympathetic part of the autonomic nervous system.

542-549 53
Abstract

Diagnosis of the blood pressure (BP) phenotype is the most important indication for its ambulatory measurement because BP phenotype is associated with cardiovascular complications and death. The study of BP phenotypes is important for patients with hypertension (HT) and comorbidity, including asthma and chronic obstructive pulmonary disease (COPD). The combination of HT with these lower airway diseases (LAD) leads to the mutual influence of pathologies creates difficulties in the drugs choice and may affect BP phenotype in HT patients.

Aim. To compare in the prospective investigation various characteristics of BP phenotype in HT patients considering LAD (asthma or COPD).

Material and methods. The prospective cohort study of ambulatory patients with HT (n=156) was carried out. The part of these patients had asthma or COPD (n=69). The clinical measurements and 24-hour BP monitoring, spirometry, clinical and biochemical blood tests, standard examination were performed, initially and after 12 months. BP phenotype were determined by the ratio of clinical BP and ambulatory BP considering their threshold values. Standard statistical methods and multivariate analysis were used.

Results. Patients with LAD had 2 times more often prognostically unfavorable phenotypes: ineffective antihypertensive therapy (AHT) 37.3% vs 15.7% and masked AHT inefficiency 7.5% vs 4.5%; white coat HT on treatment (WCH) and effective AHT were less common(29.9% vs 42.7%; 25.5% vs 37.1%, respectively, p 148 mm Hg (b=2.733, p=0.040), LAD (b=1.015, p=0.011), serum total cholesterol (b=0.350, p=0.043), degree of nighttime diastolic BP decrease (for 13.1-18.0% b=-2.130, p=0.004; for 18.1-24.0% b=-2.509, p=0.001). The factors associated with masked AHT inefficiency in comparison to effective AHT were heart rate in orthostasis >87 beats/min(b=3,512, p=0.006) and SBP in orthostasis 141-148 mm Hg (b=3.405, p=0.004).

Conclusion. The prevalence of prognostically unfavorable BP phenotypes (ineffective AHT and masked AHT inefficiency) is two times higher in HT patients with LAD. The first is associated with LAD presence, sex, and serum cholesterol; both phenotypes interrelated with hemodynamic parameters including degree of nighttime diastolic BP decrease. We found no association between AHT and LAD therapy with the BP phenotypes in this study. However, larger works in this area are required, including analysis of outcomes in long-term prospective studies.

NOTES FROM PRACTICE

550-556 64
Abstract

Patients with chronic myocarditis have a high risk of an unfavorable course of the novel coronavirus disease (COVID-19) due to the ability of the SARS-Cov-2 virus to independently cause acute myocarditis, to have a direct and cytokine-mediated cytopathic effect on the myocardium, as well as immunosuppressive therapy. At the same time, the features of the interaction of chronic myocarditis and COVID-19 have not been studied. The article describes a 31-year-old patient with a 10-year history of chronic recurrent infectious-immune myocarditis, who was on long-term immunosuppressive therapy (methylprednisolone and azathioprine in the past, then hydroxychloroquine). In May 2020, a serologically confirmed COVID-19 diagnosis was made. There were risk factors for the unfavorable course of coronavirus infection: heart failure and a history of persistent atrial fibrillation, male sex. Basic therapy with hydroxychloroquine (with an increase in its dose to 800-400 mg/day), ceftriaxone, and levofloxacin was carried out. The severity of pneumonia was moderate, despite febrile fever and severe intoxication. No relapses of arrhythmias, respiratory or heart failure were observed. Minimal laboratory (some increase in anticardial antibody titers) and echocardiographic signs of exacerbation of myocarditis without an increase in troponin T levels were revealed, which quickly regressed. It can be assumed that the maintenance immunosuppressive therapy of myocarditis with hydroxychloroquine had a positive effect on the course of coronavirus pneumonia and made it possible to avoid recurrence of myocarditis. Further study of the features of the course of the pre-existing myocarditis and pneumonia in COVID-19 is necessary.

557-563 57
Abstract

Primary hyperaldosteronism is an existence of a functional autonomous source with increased aldosterone production (full or partial) in relation to the renin-angiotensin system. Increased production of aldosterone by the adrenal cortex is the most common form of a secondary hypertension despite the low attention of internists to the problem. The success of a treatment and a prognosis of these patients depend on correct choice of screening (aldosterone/renin ratio) and clarifying diagnostic methods. There are clear algorithms for conducting these tests in accordance with Russian and International recommendations in the respective groups of patients. The purpose of this case report is to demonstrate the long way to diagnosis of primary hyperaldosteronism in a young patient with refractory hypertension, right adrenal adenoma, and clinical (convulsions, weakness) and laboratory signs of hypokalemia. It should not only have made the diagnosis easy, but it could have also absolutely justified the surgical tactics. Unfortunately, the final verification of the disease by carrying out a saline test was accomplished 13 years after the debut of hypertension and 10 years after the primary visualization of the adrenal adenoma.

ASSOCIATED PROBLEMS OF CARDIOLOGY

564-570 86
Abstract
Epidemiologic studies demonstrate that both prolonged and reduced sleep duration is associated with increased risk of excessive weight and obesity. The aim of the review was to analyze probable mechanisms of association of sleep duration and obesity elucidated in current scientific literature. Several proposed mechanisms of such an association exist: an imbalance of appetite regulating hormones resulting from decreased sleep duration; fatigue or decreased activity during the daytime, leading to sedentary behavior with decreased energy expenditure; changes in eating behavior with increased daily calorie intake. The article gives a comprehensive review of factors, mediating the association of sleep duration and obesity (age, gender, ethnic origin), studies of neurohormonal regulation of sleep in association with obesity (the influence of sleep duration on thermoregulation, appetite center – increased grelin-to-leptin ratio); the relationship of sleep with growth hormone and insulin-like growth factor-1, with hypothalamic-pituitary-adrenal axis, and non-hormonal factors, stimulating food intake. Data indicating that increased sleep duration is often associated with decreased sleep quality are presented. Besides traditional risk factors – unhealthy diet and decreased physical exercise, specific attention should be given to the problems, associated with sleep disorders to increase the efficacy of treatment and prevention of obesity.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

571-578 64
Abstract

Aim. To study the adherence of doctors to the guidelines for the treatment of chronic heart failure (СHF) and the adherence of patients with СHF to the therapy prescribed by doctors.

Material and methods. The COMPLIANCE study is an integral part of the PROFILE registry of the specialized cardiology division of the research center. The study includes patients with verified CHF who were previously observed in the PROFILE registry and patients with CHF who have been newly seeking medical care in the period from December 01, 2019 to December 31, 2020. At the first visit, the initial therapy was evaluated, treatment adherence was determined, and treatment was corrected in accordance with current guidelines. The second visit will also assess patient adherence to treatment, assess the factors of non-adherence and complications of diseases during the year of follow-up.

Results. The first 30 case-records of patients with CHF included into the study were analyzed. 90% of patients received angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB). Beta-blockers (BB) were prescribed to 96.7% of patients, and mineralocorticoid receptor antagonists (MRAs) – to 76.7% of patients, and some of them received MRAs at ejection fraction >35%. It was found that the overall adherence of patients according to the adherence scale of the Russian National Society of Evidence-Based Pharmacotherapy (NSEPh) was significantly lower than the adherence to specific drugs. The worst was adherence to ACEI (71%) and MRAs (77%), higher – to BB (86%). The most common factors of non-adherence to treatment, according to the first results, are a large number of medications and a complex medication regimen.

Conclusion. The first part of the COMPLIANCE study showed a relatively good adherence of doctors to current guidelines. However, the choice of the drug and its doses did not always correspond to evidence-based medicine data, existing guidelines and summary of product characteristics (SmPC) of specific drugs. The patients adherence to the prescribed therapy was not bad (this can be explained by long-term follow-up in specialized centers), but it was different for different drugs. The worst adherence was registered to the ACEI/ARB. This is warning factor, since these drugs make a significant contribution to improving the long-term outcome of CHF.

INNOVATIVE CARDIOLOGY

579-584 103
Abstract

Enhanced external counterpulsation (EECP) is one of the most effective and safe non-invasive methods of treatment for patients with coronary artery disease (CAD), including complicated chronic heart failure (CHF). This method of therapeutic neoangiogenesis, used in conjunction with traditional drug therapy and myocardial revascularization, can significantly improve the quality of management of these patients.

Aim. To study the effect of the EECP course on exercise tolerance, quality of life, structural and functional parameters of blood vessels in patients with verified stable CAD complicated by CHF.

Material and methods. Patients (n=70) with verified stable CAD (angina pectoris class II-III) complicated by CHF class II-III (NYHA) were included in non-randomized uncontrolled study. Data from 67 patients (48 to 74 years old; 47 men and 20 women) were included in the final analysis. All patients had a course of EECP (35 one-hour procedures with a compression pressure of 220-280 mm Hg). All patients initially and 1.5 months after the EECP course had a 6-minute walk test (6MWT), an assessment of the clinical status, quality of life of patients (MLHFQ; Minnesota Living with Heart Failure Questionnaire). Computer nailfold video capillaroscopy, photoplethysmography with pulse wave recording and contour analysis, applanation tonometry to assess central aortic systolic pressure and radial augmentation index (RAI) were performed to assess the structural and functional state of large and microcirculatory vessels.

Results. A statistically significant improvement in exercise tolerance (increase in distance in 6MWT from 212 [189; 273] to 308 [251; 336] m), improvement in the clinical status of patients (decrease in points on the rating scale of clinical state from 6.5±1.8 to 4.4±1,2), improvement in the quality of life according to the MLHFQ questionnaire (from 51.9±6.2 to 38.6±7.1), increase in the left ventricle ejection fraction (from 41.6 [36.6;47.1] to 44.8 [39.5;50.7]%) were found. A statistically significant improvement in endothelial function indices of both large vessels (phase shift: from 5.6 [2.4;7.2] to 6.8 [3.3;8] m/s) and microcirculatory vessels (occlusion index: from 1.5 [1.2;1.7] to 1.66 [1.3;1.9]), as well as a decrease in functional disorders of nailfold capillaries (percent of perfused capillaries, capillary network density in the reactive hyperemia test) also were found. But no statistically significant changes in the structural remodeling indices of both large and microcirculatory vessels were found.

Conclusion. A positive effect of the EECP course both on the functional status with an increase in exercise tolerance and improvement in the quality of life, and on the functional state of large vessels and microvasculature was found in patients with stable CAD complicated by CHF.

585-589 217
Abstract

There is evidence of a correlation between epicardial adipose tissue and the presence and severity of coronary heart disease, the development of hypertrophy, impaired diastolic and systolic function of the left ventricle, enlargement, fibrosis and electrophysiological remodeling of the atria, the occurrence and severity of supraventricular arrhythmias. There is also a lot of evidence of the influence of both non-drug methods and drugs on the severity and functional activity of epicardial adipose tissue, which can be considered as a potentially modifiable factor of cardiovascular risk, the various therapeutic interventions target and a criterion for their effectiveness. Its unique characteristics suggest the advisability of pharmacological strategies aimed at regulating the expression of genes encoding the secretion of adipocytokines and adipocyte function, and a dynamic assessment of the severity of epicardial fat during therapy can be a tool to evaluate its effectiveness in various cardiovascular diseases.

590-594 65
Abstract

The emergence of new research methods makes it possible to study the tissue, structural, cellular, and molecular causes of atrial fibrillation (AF). Recently, the role of interstitial telocyte cells in the pathogenesis of AF has been actively discussed. Telocytes are a special type of interstitial cells identified in many organs and tissues, including the heart. The roles of telocytes in the myocardium are diverse: they have pacemaker activity, and carry out structural and coordination communication between cells. The ability of these cells to change the speed of the electrical pulse in the atrial and ventricular myocardium has been proven. Telocytes form "atypical" connections with almost all types of cells in the human heart, which collects them in an integrated network. Using electron microscopy, it was found that interstitial cells have different types of connections in the network and can integrate "information" from the vascular and nervous systems, interstitial, immune system, stem cells, progenitor cells, and contractile cardiomyocytes. Currently, the results of studies have been obtained that prove both positive and negative effects of telocytes on the occurrence of various diseases of the cardiovascular system. The role of telocytes in AF arrhythmogenesis remains a subject of discussion. The unique properties of telocytes in providing intercellular contacts, transmitting genetic information, and their ability to regenerate heart tissue are undoubtedly the most promising areas of modern cardiology. There is evidence of both direct and indirect effects of telocytes on the electrophysiological properties of the myocardium. There is no doubt that the development of this area opens up new therapeutic targets for the prevention and treatment of AF.

POINT OF VIEW

595-600 94
Abstract

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

601-606 63
Abstract

Modern tactics of treatment of arterial hypertension (AH) involves the use of both monotherapy and combination therapy. Monotherapy is recommended primarily for low-risk patients with systolic blood pressure (BP)< 150 mm Hg. Monotherapy should also be preferred in very high risk patients with high normal BP and frail elderly patients. However, combination therapy is recommended for most hypertensive patients as initial therapy. Starting combination therapy is more effective in lowering BP than monotherapy. Even at low doses, it is usually more effective than maximum dose monotherapy. The most commonly prescribed combinations today contain a renin-angiotensin system blocker (angiotensin converting enzyme inhibitors or angiotensin II receptor blocker) with a calcium antagonist or diuretic. The combination of lisinopril with amlodipine not only proved its high efficiency in various international and Russian studies, but also turned out to be pharmacoeconomically more profitable. Fixed combinations of lisinopril and amlodipine are the optimal choice in the treatment of hypertensive patients, due to all the advantages of both components: higher efficacy and safety rates compared to monotherapy and better patient adherence to treatment.

607-613 48
Abstract

Modern data on comorbidity in coronary artery disease (CAD) are presented in the article, as well as its frequency, dependence on the age, clinical and prognostic significance, and increasing relevance for practical health care. The positions of one of the components of cardiovascular comorbidity – multifocal atherosclerosis – are presented. The existing approaches to the detection and clinical assessment of multifocal atherosclerosis, as well as to the management of the high risk of ischemic events in such patients, are outlined. The main positions on the prevention of the risk of cardiovascular complications in patients with CAD and atherosclerosis of the peripheral arteries using a combination of the anticoagulant – rivaroxaban and the antiplatelet agent – acetylsalicylic acid, are highlighted on the basis of the results of clinical studies. Promising possibilities of using such a therapeutic approach to the management of comorbid patients in routine clinical practice are presented.

614-622 45
Abstract

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

623-634 49
Abstract

Arterial hypertension (AH) is powerful and modifying factor of developing macrovascular and microvascular complications of diabetes. Patients with AH and diabetes belong to group with high and very high levels risk of developing cardiovascular complications and chronic kidney disease. The combination of type 2 diabetes mellitus and AH dramatically increases the risk of developing terminal stages of microvascular and macrovascular diabetic complications: blindness, end-stage chronic kidney disease, amputation of the lower extremities, myocardial infarction, cerebral stroke, worsens the patients prognosis and quality of life. There is ample evidence that blood pressure control in diabetic patients may be critical for improving long-term prognosis. This observation does not lose its relevance even with the emergence of new antidiabetic drugs with proven cardio- and nephroprotective effects. Modern clinical researchers and meta-analysis show the priority of combined antihypertensive therapy, which increases the efficacy of blood pressure correction and prophylaxis of long-term complications in patients with type 2 diabetes. In this article we want to pay attention to features of AH in patients with diabetes, to bi-directional pathogenic mechanisms, to discuss the new algorithms of the treatment and therapeutic needs of these patients. It is important to accent the understanding of the integrity and unity of pathogenic mechanisms which are needed in correction. Innovative antihyperglycemic therapy demonstrates the ability of blood pressure decrease. The synergy of effects let us successfully realize the strategy of multi-factor control and reduce a risk of micro- and macrovascular complications.

635-637 54
Abstract

The data from the observational study of M. Fralick et al. were analyzed in the article. The authors analyzed a large database of patients with atrial fibrillation and concluded that rivaroxaban is inferior to apixaban in its ability to prevent ischemic stroke and systemic embolism and is more likely to cause bleeding. Serious methodological defects of the analysis take place. No statistical methods are capable of correcting the absence of such important information in the database as the doctor's motives for prescribing a particular drug, as well as the patient's adherence to taking it. It is also noted that the patients included in the study, according to clinical characteristics, did not correspond to the typical population of patients with atrial fibrillation. The author considers the conclusions made in the mentioned work to be unauthorized.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

638-643 53
Abstract

The article presents the evolutionary development of combination therapy from the creation of a multicomponent tablet for the treatment of arterial hypertension (AH) to modern multi-target fixed combinations as the most effective approach to the fight against cardiovascular diseases (CVD). The priority of domestic scientists, in particular academician A.L. Myasnikov, in the development and creation of a combined drug for AH treatment is shown. The development of pharmacology and pharmaceutical technologies has allowed to expand the range of possible drug combinations for AH therapy, and the discovery of new pathophysiological mechanisms involved in the cardiovascular continuum has led to the understanding of the close links between AH and atherosclerosis. This fact prompted the scientific community to search for and implement in practice drug combinations that would allow multi-target therapy, that is, to influence several pathological processes and achieve a number of therapeutic goals. The presented review testifies to the transformation of the concept of fixed combinations for patients with AH into the concept of a multi-target drug. Multi-targeting is achieved not only by the pleotropic of components known as hypotensive agents, but also by combination with statins. Taking into account the wide AH prevalence in the population, its high medical and social significance, the critical importance as a risk factor for CVD, the authors consider a justified clinical and epidemiological approach to primary prevention of CVD with the widespread use of multi-targeted therapy in all high-risk patients with AH. It is expedient to develop new domestic medicines that implement the concept of a multi-targeted drug, to include them in the list of vital medicines, to increase the availability of these drugs to the population on the basis of preferential programs.

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Abstract

Current guidelines for the management of patients with dyslipidemia define low-density lipoprotein cholesterol (LDL-C) as the primary target in addressing lipid-lowering therapy. The target level of LDL-C in real clinical practice is achieved in no more than a third of patients who have undergone a coronary event and receive high-intensity lipid-lowering therapy. Achieving the goals of lipid-lowering therapy in a significant proportion of patients with atherosclerotic cardiovascular diseases (ACVD) is impossible with the use of even high doses of statins, which requires its enhancement by other drugs. The article considers the place of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the prevention of cardiovascular diseases in patients with ACVD in accordance with the latest Russian and international guidelines. A modern decision-making algorithm for the initiation of PCSK9 inhibitors therapy in patients with ACVD is presented. The authors provide a clear understanding about the patient populations that will benefit most from the taking of PCSK9 inhibitors. Particular attention is paid to Guidelines for the management of dyslipidemias developed by European Society of Cardiology and European Atherosclerosis Society in 2019. The issues of patients provision with PCSK9 inhibitors with reference to Russian conditions are described in details in accordance with the requirements for territorial programs of state guarantees. Further improvement in the provision of PCSK9 inhibitors to patients with indications for this therapy is necessary, considering the potential of these drugs in reducing cardiovascular morbidity and mortality in patients with ACVD.

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Abstract

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

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2020-08-11

Dear colleagues!

We invite you to take part in the work of the 
Annual All-Russian Scientific and Practical Conference "Cardiology on the March!" and the 60th Session dedicated to the 75th Anniversary of the National Medical Research Center of Cardiology” of the Russian Ministry of Health 
September 9-11, 2020
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