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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 6 (2020)
View or download the full issue PDF (Russian)

ORIGINAL STUDIES

868-875 464
Abstract

Aim. To study associations between calcification of the coronary arteries (CA), the state of the peripheral vascular wall and bone strength indices.
Material and methods. In a cross-sectional study were included 200 women at the age 45-69 y.o. who were observed on an outpatient basis and signed informed consent. A survey was conducted on the presence of cardiovascular risk factors and the risk of fractures. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. The presence of calcium deposits in coronary vessels was determined by multispiral computed tomography (MSCT) using the Agatston index. The bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. The marker of bone resorption C-terminal telopeptide of type-1 collagen (СТх) was determined in blood serum by the β-crosslaps method.
Results. There was a positive correlation between the parameters of vascular stiffness, subclinical atherosclerosis of peripheral vessels and CA calcification: AI and calcium index (r=0.25, p<0.05), IMT and calcium index (r=0.23, p<0.05), presence of AP and calcium index (r=0.26, p<0.05). The PWV increased as the calcium index increased, but the correlation remained at the trend level. Women with low bone mass had higher PWV (p<0.05), AI (p<0.01), IMT (p<0.02), CTx level (p<0.001) and a higher number of AP than those with normal BMD. CTx was inversely correlated with PWV and calcium index (p<0.05). Based on multivariate linear regression analysis (adjusted for age, menopause duration, low body weight, smoking factor and total cholesterol) the independent nature of the relationship between the Agatstone index and BMD in all the measured parts of the skeleton, between AI and BMD of HN, and between IMT and BMD of HN was confirmed. The relationship between the marker of bone resorption CTx and BMD of the spine and PH remained highly reliable.
Conclusion. The correlation of stiffness indices and subclinical atherosclerosis of peripheral arteries, which is a predictor of high risk of cardiovascular events, allows to suggest an important role of changes in the peripheral vascular wall in increasing cardiovascular risk. A decrease in BMD and an increase in the marker of bone resorption, associated with an increase in indices of vascular stiffness and subclinical atherosclerosis and, especially, CA calcification, allows us to think about the common mechanisms of development and progression of atherosclerosis and osteoporosis. Therefore, early examination of women with a high cardiovascular risk, assessed by the SCORE scale, after 45 years and before menopause to detect vascular rigidity and the presence of subclinical atherosclerosis, and performing x-ray densitometry for individuals with changes in these indices will allow stratify the risks of atherosclerosis and osteoporosis complications and recommend preventive use of drugs that reduce vascular rigidity and increase BMD.

876-880 287
Abstract

Background. Left ventricular (LV) remodeling is an adverse consequence after acute myocardial infarction.
Aim. To assess the role of speckle tracking in the evaluation of LV remodeling after streptokinase infusion in patients with acute anterior ST-segment elevation myocardial infarction (STEMI).
Material and methods. A total of 200 patients with first acute anterior STEMI received streptokinase as a reperfusion therapy were included. Conventional echocardiography and speckle tracking were performed within 3 days of admission and 3 months later. According to the development of LV remodeling, patients were classified into two groups. Group (I) patients with LV remodeling (60 patients) and group (II) patients without remodeling (140 patients).
Results. Patients with LV remodeling had lower global longitudinal (GLS) and circumferential (GCS) strain values (-13.19±4.57 vs. -18.90±4.23 % and -13.16±4.27 vs. -17.16±3.3 %, respectively, p<0.001). GLS cutoff value of >-13.5 was shown to have the best diagnostic accuracy (sensitivity =60.0% & specificity =87.1%) in predicting LV remodeling (AUC 0.816, 95% confidence interval [CI] 0.754-0.877, p<0.001). GCS cutoff value of >-16.21 was shown to have the best diagnostic accuracy (sensitivity =75.0% & specificity =71.4%) in predicting LV remodeling (AUC 0.785, 95%CI 0.719-0.85, p<0.001).
Conclusion. Speckle tracking echocardiography either longitudinal or circumferential strain has good sensitivity and specificity in predicting LV remodeling after acute myocardial infarction.

881-887 145
Abstract

Surgical care is associated with a high risk of complications. In 2014 the updated joint ESC/ESA guidelines on preoperative assessment and perioperative management of patients were published to improve patient safety in non-cardiac surgery. The increase in the adherence to clinical guidelines promotes the improving of the healthcare quality and safety improvement.
Aim. To study physicians' level of adherence to ESC/ESA clinical guidelines for preoperative assessment and perioperative management of patients.
Material and methods. A retrospective observational study included 102 patients admitted to Moscow general hospital from 01.03.2019 to 30.06.2018 for elective surgery. All of them underwent preoperative examination in outpatient department of the hospital and had at least one concomitant disease requiring drug therapy. The medical records data on the preoperative examination and perioperative treatment with beta-blockers, HMG CoA reductase inhibitors and angiotensin-converting-enzyme (ACE) inhibitors/ angiotensin receptor blockers (ARBs) were analyzed for compliance with the ESC/ESA guidelines.
Results. A standardized cardiac risks assessment was not documented in the results of preoperative examination. Electrocardiography (ECG), echocardiography and non-invasive stress tests were performed according to clinical guidelines in 100%, 77.8% and 25% of cases, respectively. Unnecessary ECG and echocardiography were prescribed in 50.5% and 72% of cases, respectively. Appropriate correction of ACE inhibitors/ARBs therapy was performed in 66.7% patients with congestive heart failure and only in 2.7% with arterial hypertension. In 19 patients with ischemic cardiac disease, 13 (84.2%) patients received HMG CoA reductase inhibitors and 16 (68.4%) ones received beta-blockers during hospitalization. Inappropriate omission of statins, beta-blockers and ACE inhibitors (ARBs) during hospitalization was registered in 22.2%, 11% and 4.9% patients, respectively.

Conclusion. The number of inappropriate ECGs and echocardiographies, as well as incorrect treatment with beta-blockers, HMG CoA reductase inhibitors and ACE inhibitors (ARBs) in perioperative period evidence that the adherence of physicians to the clinical guidelines on preoperative assessment and perioperative management of patients remains low.
It is reasonably to develop risk-based interdisciplinary protocols for preoperative examination, algorithms for interdisciplinary communication and interaction between specialists and the healthcare levels, as well as physicians' education for better adherence to clinical guidelines.

888-898 210
Abstract

Aim. To study comorbidity, drug therapy and outcomes in patients with atrial fibrillation (AF) included in the outpatient and hospital RECVASA registries.
Material and methods. Patients with AF (n=3169; age 70.9±10.7 years; 43.1% of men) in whom comorbidity, drug therapy, short-term and longterm outcomes (follow-up period from 2 to 6 years) were included in hospital registers RECVASA AF (Moscow, Kursk, Tula), as well as outpatient registers RECVASA (Ryazan) and RECVASA AF-Yaroslavl.
Results. Outpatient registries (n=934), as compared to hospital registries (n=2235), had a higher average age of patients (73.4±10.9 vs 69.9±10.5; p<0.05), the proportion of women ( 66.2% vs 53.0%; p<0.0001) and patients with combination of 3-4 cardiovascular diseases (CVD), including AF (98.0% vs 81.7%, p<0.0001), and also with chronic noncardiac diseases (81.5% vs 63.5%, p<0.0001), the risk of thromboembolic complications (CHA2DS2-VASc 4.65±1.58 vs 4.15±1.71; p<0.05) and hemorrhagic complications (HAS-BLED 1.69±0.75 vs 1.41±0.77; p<0.05), as well as a lower frequency of prescribing appropriate pharmacotherapy for CVD (55.6% vs 74.6%, p<0.0001). During the observation period, 633 (20.0%) patients died, and in 61.8% of cases - from cardiovascular causes. The mortality rate in one year in Moscow was 3.7%, in Yaroslavl - 9.7%, in Ryazan - 10.7%, in Kursk - 12.5% (on average for four registers - 10.3%). A higher risk of death (1.5-2.7 times) was significantly associated with age, male sex, persistent AF, history of myocardial infarction (MI) and acute cerebrovascular accident (ACVE), diabetes mellitus, chronic obstructive disease lungs (COPD), heart rate>80 bpm, systolic blood pressure <110 mm Hg, decreased hemoglobin level. A lower risk of death (1.2-2.4 times) was associated with the prescription of anticoagulants, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), betablockers, statins. The number of cases of stroke and MI was, respectively, 5.1 and 9.4 times less than the number of deaths from all causes. The higher risk of stroke in patients with AF during follow-up was significantly associated with female sex (risk ratio [RR]=1.61), permanent AF (RR=1.85), history of MI (RR=1.68) and ACVA (RR=2.69), HR>80 bpm (RR=1.50). Anticoagulant prescription in women was associated with a lower risk of ACVA (if adjusted for age: RR=0.54; p=0.04), in contrast to men (RR=1.11; p=0.79).
Conclusion. The majority of patients with AF registries in 5 regions of Russia had a combination of three or more cardiovascular diseases (73.9%), as well as chronic non-cardiac diseases (68.8%). The frequency of proper cardiovascular pharmacotherapy was insufficient (68.6%), especially at the outpatient stage (55.6%). Over the observation period (2-6 years), the average mortality per year was 10.3%, but at the same time it differed significantly in the regions (from 3.7% in Moscow to 9.7-12.5% in Yaroslavl, Ryazan and Kursk). Cardiovascular causes of deaths occurred in 62%. A higher risk of death (1.5-2.7 times) was associated with a history of stroke and MI, diabetes mellitus, COPD, heart rate>80 bpm, systolic blood pressure <110 mm Hg, decreased hemoglobin level. However, the risk of death decreased by 1.2-2.4 times in cases of prescription of anticoagulants, ACE inhibitors / ARBs, beta-blockers and statins. The risk of ACVA and MI was the highest in the presence of the history of this event (2.7 and 2.6 times, respectively). Anticoagulant prescription was significantly associated with a reduced risk of stroke in women.

899-907 228
Abstract

Aim. To study the association of smoking with indicators of the structure and function of blood vessels in a sample of middle-aged men.
Material and methods. This study is part of a 32-year prospective cohort observation of males starting in childhood (11-12 years). The study included 301 (30.0%) representatives of the original population sample aged 41-44 years. The examination included a survey on a standard questionnaire with an assessment of the status and intensity of smoking, of anthropometric indicators, blood pressure (BP), and determination of the blood lipid spectrum. The stiffness of the arterial wall and central pressure were measured by the method of applanation tonometry. The carotid intima-media thickness of the common carotid artery (C-IMT) was estimated by the method of ultrasonic duplex scanning of the main vessels of the neck.
Results. Of the 301 men examined, aged 41-44 years, 92 (30.6%) people never smoked, 73 (24.3%) smoked in the past and 136 (45.2%) people currently smoke. Former smokers were divided by the intensity of smoking in the past as follows: less than 20 cigarettes/day were smoked by 41 (56.0%) people, and ≥20 cigarettes/day - 32 (44.0%) people. Among current smokers, less than 20 cigarettes/day were smoked by 63 (46.0%) people, and ≥20 cigarettes - 73 (54.0%) people. Current smokers have a statistically significantly higher level of triglycerides and lower cholesterol of high density lipoproteins in the blood, augmentation index (AIx), augmentation blood pressure and C-IMT thicker than non-smokers. The thickness of the C-IMT and AIx was statistically significantly greater among current smokers who smoked 20 or more cigarettes daily. Men who smoked in the past had significantly greater body weight, waist circumference and pulse wave velocity. 12.4% of AIx variability was attributable to current smoking combined with variability in alcohol consumption, blood glucose, and heart rate. The body mass index (BMI) and ethanol consumption are independent determinants of peripheral and central systolic pressure, and account for 17.8% and 18.6% of their variance, respectively. The combined contribution of current smoking, age, BMI, low-density lipoprotein cholesterol and plasma glucose to the thickness variability of C-IMT was 13.7%. Among men with a smoking duration in the past >10 years, the levels of total cholesterol, triglycerides and arterial stiffness indicators - AIx, pulse pressure amplification were higher compared to peers with a shorter smoking duration.
Conclusion. Current smoking is associated with atherogenic changes in the blood lipid spectrum, impaired structure and function of the main arteries. Moreover, the severity of structural and functional disorders of the arteries is associated with the intensity of current smoking. If you give up smoking, there is a potential possibility of reversibility of these vascular disorders.

908-915 261
Abstract

Aim. To study the factors associated with contrast-induced acute kidney injury in elderly patients with acute coronary syndrome (ACS).
Material and Methods. A retrospective analysis of 514 electronic medical records of patients aged 75 years and over (38% men and 62% women) with confirmed acute coronary syndrome has been performed. The contrast-induced acute kidney injury was defined as an increase in serum creatinine ≥26.5 μmol/L in 48 h or as an increase in serum creatinine in 1.5 times within 7 days after the contrast media exposure. Patients were divided into contrast-induced acute kidney injury and non-contrast-induced acute kidney injury group. Clinical characteristics and in-hospital outcomes were extracted from patients' medical records. Procedural characteristics were obtained from laboratory database.
Results. Angiographic intervention was performed in 74% of patients, 32% of them (more often in women, p=0.033) were diagnosed with contrast-induced acute kidney injury. Patients with contrast-induced acute kidney injury are characterized by a higher death rate (17% и 3%, p<0.001) and were more likely to have heart failure with reduced ejection fraction (34% и 21%, p=0.008) and acute heart failure (Killip class II-IV) (24% и 16%, p=0.015). The risk of developing contrast-induced acute kidney injury was related the volume of contrast medium administered.
Conclusions. Prevention particular care should be taken to female patients older than 75 years with ACS, with a history of the chronic heart failure with reduced ejection fraction or acute heart failure (Killip class II-IV), and with a high volume of contrast media, highlighting that a perioperative comprehensive management strategy is needed to improve the prognosis.

916-924 291
Abstract

Aim. The aim of our study was to continue a comparative analysis of availability and access to cardiovascular medicines in 2017 and 2018 in the city of Kazan according to the original WHO/HAI methodology to assess the effectiveness of government interventions to ensure access to medicines.
Material and methods. We performed a comparative analysis of prices of cardiovascular medicines in 2017 and 2018 in Kazan using the World Health Organization and Health Action International (WHO/HAI) methodology, to assess medicines' availability and affordability to ensure their rational use. We studied availability and prices of 71 cardiovascular medicines in public and private pharmacies in the city of Kazan and analyzed procurement prices of these medicines in hospitals. Also we studied the affordability of medicines, as well as performed pharmacoeconomic cost-minimization analysis for arterial hypertension pharmacotherapy in 2018. For each name, we studied the prices for the original brand and its lowest-priced generic. We compared medicine prices with international reference, delivered by the Management Sciences for Health and by expressing them as median price ratio (MPR).
Results. In the public sector, prices of generic medicines were at the level of reference prices with the indicators of MPR 1.14 [0.41-1.84] and 1.17 [0.49-2.21], in 2017 and 2018 respectively. In the private sector, prices of generics reduced 2 times in 2018 compared to 2017, with the decrease in MPR from 2.22 [1.12-3.91] to 1.25 [0.44-2.32], (p<0.05). In the public sector, the affordability indicators of generics were the same in the studied years (Me=0.24 in 2017 and Me=0.26 in 2018). However, in the private sector there was a 2.5 times reduction in the affordability of generics (reduction Me from 0.66 to 0.24, p<0.05) in 2018 compared to 2017. From 2017 to 2018 the affordability of original brands changed from 1.9 to 1.3 in the public sector and from 2.3 to 1.5 in the private sector, but this change was not statistically significant (p>0.05). In 2018, depending on the choice of the medicine the annual course of therapy of hypertension varied from 149 to 28835 rubles.
Conclusions. In 2018, the prices of generic cardiovascular medicines, but not of originator brands, reached the level of reference prices in both the public and private sectors of Kazan. According to the WHO/HAI methodology, generic cardiovascular medicines became affordable. In the private sector, there was a reduction in the prices of generic medicines, but not of originator brands, with an improvement of affordability of generics in 2018 compared to 2017.

NOTES FROM PRACTICE

925-930 109
Abstract

Aim. To study indicators of epithelial dysfunction in the proximal renal tubules by determining the activity of organ-specific enzymes neutral α-glucosidase (NAG) and L-alanine aminopeptidase (LAAP), in patients with the initial stage of chronic heart failure in dyslipidemia, and the possibility of reducing with simvastatin.
Material and methods. The study involved 90 subjects, who were divided into control and main groups. The control group consisted of 30 practically healthy individuals, the main group was divided into 2 subgroups: patients with stage I chronic heart failure (CHF) without type 2 diabetes mellitus (DM2) and patients with CHF with DM2. Patients of each of the main subgroups received simvastatin 20-40 mg/day in addition to treatment of the main pathology. The main group included patients with a total serum cholesterol level of more than 6.0 mmol/l, a BMI level of more than 30 kg/m2, and who had not previously taken statins. The exclusion criterion was a violation of the filtration capacity of the kidneys and the presence of gross dysfunction of organs and systems of the body. The functional state of the proximal renal tubules was assessed by the concentration of NAG and LAAP in dialized urine.
Results. Initially, the level of activity of renal enzymes in representatives of both major subgroups is higher than the group of practically healthy individuals. Taking simvastatin in the CHF without DM2 subgroup does not cause an increase in enzyme activity throughout the entire observation period, either at a daily dosage of 20 mg (NAG - 12.36±2.65 ncat/1 14.1±5.23 ncat/1 and after 3 and 6 months, LAAP - 9.4±1.62 and 11.2±2.99 ncat/1 after 3 and 6 months), or at a dosage of 40 mg/day (NAG - 30.47±3.85 and 26.2±6.75 ncat/1 after 3 and 6 months; LAAP -17.3±3.56 and 19.58±3.83 ncat/1 after 3 and 6 months). Taking simvastatin 20 mg/day in patients with CHF with DM 2 causes an increase in the NAG activity: 26.68±6.03 and 34.57±9.73 ncat/1 after 3 and 6 months). Taking simvastatin 40 mg/day increase both enzyme activity: NAG -34.3±8.7 and 46.94±9.02 ncat/1 after 3 and 6 months, LAAP - 17.08±5.81 and 22.41±4.89 ncat/1 after 3 and 6 months).
Conclusion. The appointment of simvastatin in patients with dyslipidemia on the background of obesity is permissible in order to normalize lipid metabolism. Safe for the functional state of the proximal renal tubules, long-term administration of simvastatin, within the limits of medium-therapeutic dosages, is possible for patients without type 2 diabetes. Long-term use of simvastatin in patients with dyslipidemia on the background of type 2 diabetes mellitus has a negative effect on the epithelium of the proximal renal tubules, in the form of an increase in the activity of renal organ-specific enzymes, which indicates an increased dystrophy of the epithelium.

931-937 211
Abstract

Aim. To evaluate the single pill combination with lisinopril, amlodipine and indapamide ability in additional angioprotection achievement in patients with arterial hypertension and high pulse wave velocity (PWV) regardless on previous antihypertensive therapy (AHT).
Material and methods. To the open non-randomized study duration 12 weeks 40 patients were included taking triple AHT during 6 months. All participants underwent ambulatory 24 hour blood pressure (BP) monitoring, applanation tonometry (augmentation index and central BP), pulse wave velocity assessment, laboratory tests (HbA1c, serum uric acid, high sensitive C-reactive protein [hsCRP], serum uric acid).
Results. We observed additional systolic BP (SBP) and diastolic BP (DBP) reduction by 16.9% and 22.11% on lisinopril, amlodipine and indapamide single pill combination. Lisinopril, amlodipine and indapamide single pill combination decreased 24 h mean SBP by 16.77%, and 24 h mean DBP -23.5% (ABPM data), PWV by 19.7%, augmentation index by 14.81%, central SBP by 11.9% (p<0,05). There were positive changes in hsCRP level (-13.0%, p<0.05) and serum uric acid (-9.0%, p<0.05).
Conclusion. Lisinopril, amlodipine and indapamide single pill combination provided control BP, arterial elastic properties improving (augmentation index, PWV, central BP) and favorable influence on inflammation and serum uric acid level.

ASSOCIATED PROBLEMS OF CARDIOLOGY

938-947 287
Abstract
Chronic kidney disease (CKD) is characterized by increasing prevalence, catalyzing properties in relation to cardiovascular and general mortality, and, in most cases, is asymptomatic, which means late diagnostic verifiability. The global average prevalence of CKD is 13.4%, and CKD C3-5 is 10.6%. The main causes of CKD C5 are diabetes mellitus (DM, 46.9%), hypertension (28.8%) and to a lesser extent, glomerulonephritis (7.1%) and polycystic diseases (2.8%), while other causes account for a total of 14.4%. Despite the simple diagnosis of CKD, one of the key problems of modern therapeutic and pediatric clinics is its low detection rate at the early stages, which, according to some data, reaches 96.6%. This review provides data on the criteria for the diagnosis of CKD, as well as more detailed consideration of the course of CKD in patients with DM, hypertension, and heart failure. Attention is paid to the medicinal origin of CKD, as well as to the development of anxiety and depressive disorders in CKD. General issues of treatment of patients with CKD are considered in detail. Lifestyle changes are an important part of the fight against the development and progression of CKD. Currently, Smoking, alcohol, and physical inactivity have been shown to have a harmful effect on the risk of developing and progressing CKD. Diet plays a certain preventive role. The main drugs with nephroprotective properties are angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists. Both classes of drugs are effective in proteinuric forms of nephropathies and in combination/association of CKD with diabetes or hypertension. The review also provides data on the nephroprotective properties of mineralocorticoid receptor antagonists, endothelin receptor antagonists, and sodium-glucose co-transporter-2 inhibitors. Given the high importance of identifying and effectively treating patients with CKD, it is necessary to focus on early detection of CKD, especially in high-risk groups. It is necessary to raise public awareness by creating and implementing programs for primary prevention of CKD, as well as awareness of patients, motivating them to follow the doctor's recommendations for a long time, including as part of the implementation of a non-drug strategy to combat CKD. It is important to use the full range of methods of drug therapy for CKD, including measures of universal nephroprotection. It should be remembered that the cost of late diagnosis of CKD is a reduction in life expectancy, primarily due to high rates of cardiovascular mortality, disability, and high-cost medication and kidney replacement therapy.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

948-957 317
Abstract

Aim. To analyze hospital admission and ambulatory care of the patients with arterial hypertension (AH) in federal districts and regions from the perspective of the WHO concept of diseases, which can be treated in ambulatory settings (ambulatory care sensitive conditions, ACSC).
Material and methods. For analysis we used data from annual forms of federal statistical monitoring (12 and 14), which includes data on hospital admissions with hypertension in federal districts and separate regions in 2017. Hypertension included diseases characterized by raised blood pressure, ICD10: I10-I13.
Results. We performed the analysis of 12 and 14 forms per districts and regions of the Russian Federation. Regions with increased hospitalization rates and an increased ratio of the hospitalizations to number to outpatients visits were identified. High variability of these indicators was observed both among both between regions and federal districts. The values of the ratio indicator vary from 0.0131 in the Nizhny Novgorod Region to 0.0234 in the Chechen Republic. The average value of the ratio in the federal district varies from 0.032 in the Volga Federal District to 0.119 in the North Caucasus Federal District. In the North Caucasus and Far East Federal District the value of the indicator is significantly higher than in other districts.

Conclusion. Assessing diseases which can be treated in ambulatory setting scan be one of the tools for evaluating the quality of medical care in primary care facilities. However, before including ACSC as an indicator of the quality of health care delivery, a deeper understanding of the reasons that can impact its rates is required.

958-965 172
Abstract

Nutrition is one of the most significant factors influencing the state of health, the development of diseases and the generally the human longevity. The nature of nutrition, which has a protective effect, is the basis of the healthy diet. Among healthy nutritious rations, there are those that have developed naturally, formed from the cultural food heritage and later were made in scientific nutritional recommendations. These are such diets as the Mediterranean type of food, the Scandinavian diet, the Tibetan style of food, etc. At the same time, there are diets specially developed by specialists for specific purposes. All of them correspond to the basic principles of the healthy diet: balance, usefulness and energy balance. This article offers an overview of the use of individual diets that have been developed by nutritionists, such as the intermittent fasting diet, the Paleo diet, and the DASH (Dietary Approaches to Stop Hypertension) diet. The article discusses the differences and advantages of these dietary approaches, presents the results of effectiveness, considers the limitations and features of their use.

966-976 160
Abstract

High salt intake is an important risk factor for cardiovascular diseases (CVD), closely related to the level of blood pressure in the population. The purpose of the review: to study population-based interventions for CVD prevention, aimed at reducing salt intake; to assess the potential for their implementation in the Russian Federation. We presented population-based strategies for dietary salt intake reduction used in different countries. The main components of strategies aimed to correct this risk factor in the Russian Federation were identified. The main components of the population-based approach to reducing salt intake are: determining population salt consumption, identifying sources of salt in the diet, monitoring of salt content in products, engaging with the food industry, consumer awareness campaigns, changes in product labeling, tax measures. An integrated approach to the problem is the most successful. Measures which were highly effective have not yet been fully implemented in the Russian Federation. At the moment, taxation of high-salt foods and tax subsidies for healthy food are not applied. Food manufacturers are not sufficiently involved - there are no legislatively introduced measures to reduce salt through food reformulation. Firstly it has to be applied to diet-forming products that are consumed daily, such as bakery and dairy products, and meat products.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

977-983 140
Abstract

Aim. Based on the data of the TRUST study (Influence of Participation in Randomized Controlled Trials on adheRence to Medicines' Intake and regUlar viSits to the docTor) to assess the quality of drug therapy and patients' awareness of achieving target blood counts and blood pressure (BP) among patients with coronary artery disease (CAD), diabetes mellitus (DM), hypertension.
Material and methods. 102 patients are enrolled in the study group of the TRUST study who participated in one or more randomized clinical trials (RCT) in the period from 2011 to 2018. A control group (n=109) included patients who had never participated in an RCT was selected. From January to April 2020, face-to-face or telephone contact was established with patients from both groups. In the study group, the response was 86.3%, in the control group - 81.7%. The adherence to drug therapy accordingly to current clinical guidelines was analyzed in patients with coronary artery disease in both groups.
Results. Patients with CAD who previously participated in RCTs take drugs with proven efficacy significantly more often than patients who did not participate in clinical trials. All groups of drugs intake was significantly more frequent in the study group than in the control group: angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (odds ratio [OR] 7.66, 95% confidence interval [CI] 2.5-22.6; p=0.006), statins (OR 5.12, 95%CI 1.8-14.5; p=0.002), beta-blockers (OR 2.96, 95%CI 1.03-8.5; p=0.038), antiplatelet agents (OR 2.94, 95%CI 1.1-7.7; p=0.026). In the main group, 54.3% of patients with CAD knew about their level of low-density lipoprotein cholesterol (LDL-c), and 68% of them had an LDL level of ≤ 1.8 mmol/l. Patients with DM in 92.9% of cases were aware of their glucose level, and in 76.9% of them had the fasting glucose level <7 mmol/L. Hypertensive patients in 92.8% of cases controlled their blood pressure twice a day and 89.2% of them had a target blood pressure level (<140/90 mm Hg).
Conclusion. Patients who participated in RCTs showed better adherence to treatment and health awareness compared to the control group. Partly, the approach to patient management, as it takes place in the RCTs model, can be implemented in real clinical practice to improve the quality of therapy in patients with cardiovascular disease.

POINT OF VIEW

984-993 160
Abstract

The administration of oral anticoagulants in elderly patients with geriatric syndromes such as senile asthenia syndrome, falls and high risk of falls, dementia, polymorbidity, polypharmacy are discussed in the article. The evidence base for the anticoagulants taking in patients with atrial fibrillation aged ≥75, ≥80, ≥85 and ≥90 years, in patients with atrial fibrillation and various geriatric syndromes, as well as in elderly patients with venous thromboembolic complications and frailty syndrome is presented. Most studies indicate significant advantages of direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) over the vitamin K antagonist warfarin in elderly patients with geriatric syndromes. An updated version of the FORTA consensus document, which aims to optimize the prescription of medicines for the elderly, is also presented. Apixaban has a FORTA-A safety class and is the safest oral anticoagulant in elderly patients.

994-1001 224
Abstract

In the current clinical guidelines for arterial hypertension, diuretics are considered one of the first line antihypertensive drugs, which are equivalent in their effectiveness to other main pharmacological classes used in the treatment of this disease. To date, much attention is paid to both the antihypertensive potential of diuretics and their safety profile and ability to influence prognosis. In this regard, a rational approach to the consideration of the clinical and pharmacological properties of these drugs is the isolation of thiazide and thiazide-like drugs among them, which is reflected in international clinical guidelines. Among thiazide-like diuretics, indapamide occupies a special place, favorably distinguished by its antihypertensive properties, metabolic neutrality, as well as the ability to improve the prognosis and favorably influence hard endpoints in the form of mortality rates in patients with hypertension. A unique feature of indapamide is also the presence, in addition to the direct diuretic effect, pleiotropic properties, including, in particular, some antagonism towards calcium and beneficial effects on arteries. This drug has been studied in a large number of studies, including such "difficult" categories of patients as the elderly and patients with diabetes mellitus, where indapamide has proven its powerful target-organ protective potential and metabolic neutrality, distinguishing it among both thiazide-like and thiazide diuretics. Indapamide provides a comprehensive target-organ protection at the level of the heart, blood vessels, kidneys and brain. Based on this, it can be expected that the widespread use of this drug as part of a first-line combination antihypertensive therapy will not only achieve target blood pressure levet in most patients with hypertension, but also provide an improved prognosis and improve the quality and duration of their life.

1002-1008 240
Abstract

After suffering pulmonary embolism (PE), doctors are confronted with various consequences of the disease, from asymptomatic residual pulmonary thrombosis to the formation of chronic thromboembolic pulmonary hypertension (CTEPH). There is also a subgroup of patients who have undergone pulmonary embolism, who experience shortness of breath during physical exertion, absent before pulmonary embolism, or shortened dyspnea preceding PE, combined with residual thrombosis of pulmonary artery (PA) and normal average pressure in PA at rest during catheterization of the right heart (CRH). This condition is defined as chronic thromboembolic pulmonary disease or post thromboembolic syndrome. Pathogenetic aspects of this condition are not fully investigated. It is important to predict the development of postembolic syndrome and to develop algorithms for the diagnosis, treatment and rehabilitation of patients with symptoms and residual pulmonary thrombosis. In case of the development of pulmonary vasculopathy in some patients who have undergone pulmonary embolism, a severe life-threatening condition forms - CTEPH, characterized by an increase in pressure in the pulmonary artery, right heart failure due to the presence of organized blood clots that have entered the pulmonary vascular bed during PE. The volume of thrombotic masses does not always correlate with clinical symptoms, which indicates the importance of microvascular remodeling. If CTEPH is suspected, a diagnostic algorithm is required, including ventilation-perfusion scintigraphy, CT angiopulmonography and catheterization of the right heart. Treating a patient with CTEPH is a difficult task fora doctor. The timely referral of the patient to the center where they are involved in treatment, including surgery and CTEPH is extremely important. Timely performed thrombendarterectomy in some cases allows to completely cure the patient. In the case of inoperable CTEPH or residual pulmonary hypertension after thrombendarterectomy, balloon angioplasty of the PA is used as well as drug treatment with specific drugs that reduce the pressure in the PA (riociguat), endothelin receptor antagonists (bosentan, macitentan), prostanoids (inhalant illoprost) phosphodiesterase-5 inhibitor and combined therapy. In this article we considered some consequences directly related to PE: asymptomatic residual pulmonary thrombosis, chronic thromboembolic pulmonary disease, chronic thromboembolic pulmonary hypertension.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

1009-1016 201
Abstract

The article is devoted to topical issues of management of patients with pulmonary arterial hypertension and strategies for switching to riociguat therapy in patients with insufficient clinical response against the background of phosphodiesterase type 5 (PDE-5) inhibitors. The role of the NO metabolic pathway in the development of pulmonary arterial hypertension (PAH) was shown. From the standpoint of pathogenesis, the importance of the effect of medication on this pathway through soluble guanylate cyclase (sGC) has been assessed. The effects of the drug riociguat, the only member of the sGC stimulant class approved for the treatment of PAH, are associated with a dual mechanism of action: riociguat sensitizes the sGC enzyme to endogenous NO by stabilizing the NO-sGC bond, and also directly stimulates the latter through another site of the bond, regardless of NO. The favorable efficacy and safety profile of riociguat has been demonstrated in the PATENT-1,2 studies. During therapy, patients showed an improvement in exercise tolerance, functional class, and a number of other indicators. Studies that indicate the feasibility of using a change in therapy in clinical practice are reviewed. In particular, the article provides a detailed analysis of the REPLACE study. It demonstrated a significantly greater likelihood of achieving clinical improvement and a significant decrease in the rate of development of clinical deterioration when switching patients with PAH from PDE-5 inhibitors to riociguat. This therapy was well tolerated and can be considered as a strategy for managing patients at intermediate risk with insufficient patient response to PDE-5 inhibitors. In conclusion, the need to plan the need for specific therapy for pulmonary arterial hypertension in the region is noted in order to rapidly escalate therapy to achieve a low risk of mortality in these patients.

1017-1023 159
Abstract

Dual antiplatelet therapy is the most important step in acute coronary syndrome (ACS) treatment. The new generation of inhibitors of P2Y12 platelet receptors (prasugrel and ticagrelor) provide more pronounced platelet inhibition than clopidogrel. The drugs differ in pharmacodynamics and platelet reactivity tests due to different mechanisms of binding to P2Y12 receptors. The antiplatelet effect of prasugrel and ticagrelor provides clinical benefit and better prognosis in patients with various forms of ACS. In patients with ST-segment elevation ACS prasugrel and ticagrelor are preferred over clopi-dogrel due to their higher efficacy and better clinical outcomes, and currently have preferential positions in guidelines compared to clopidogrel. The comparison of prasugrel versus ticagrelor (ISAR-REACT 5 trial) demonstrated superiority of prasugrel over ticagrelor in patients with ST-segment elevation ACS, for whom an invasive evaluation is planned and in early invasive treatment non-ST-segment elevation ACS. The choice of a drug for dual antiplatelet therapy in various clinical situations remains controversial. The latest ESC guidelines on non-ST elevation ACS (2020) [1] demonstrate the possible preference for prasugrel in patients with ACS without ST-segment elevation undergoing percutaneous coronary intervention. Current article demonstrates the results of recent clinical studies and the real clinical data regarding antiplatelet therapy in patients with coronary interventions. The indications for the use of P2Y12 platelet inhibitors in certain groups of patients are outlined. Treatment selection of the most effective and safe drugs in patients with ACS is highlighted according to the updated European guidelines.

1024-1030 134
Abstract

Today, optimal duration of double antiplatelet (DAPT) and triple antithrombotic therapy (TATT) in patients with acute coronary syndrome (ACS) remains the subject of scientific and practical discussion on possibilities of ischemic and hemorrhagic risks assessment. Good clinical risk metrics is based on validated risk scales. However, actual clinical guidelines do not provide a universal and generally accepted scale for assessing the balance of risks of ischemic events and bleeding. Is very necessary to determine the optimal content and DAPT or TATT duration is the existence of validated risk assessment scales would allow to optimize the accuracy of risk assessment of ischemic and hemorrhagic events in patients after ACS. One of the probable reasons is absence of validation of existing scales for each specific population of patients with ACS. In this regard, the use of «new» risk assessment systems: PRECISE DAPT and DAPT, in addition to the routine risk assessment scales (GRACE, CRUSADE), could become optimal in all ACS patient categories. In order to identify the initial risk of community-acquired hemorrhagic events during the first 12 months all patients with ACS at the inpatient stage of treatment is used the PRECISE DAPT score. In order to determine the need for prolongation of the standard DAPT. It should be used after 12 months of receiving DAPT in survivors of ACS patients without ischemic events, must be used the DAPT score.

1031-1038 191
Abstract

Anticoagulant therapy in elderly patients with atrial fibrillation and concomitant diseases is often the challenge for clinicians. The high risk of stroke is inherent in atrial fibrillation, and it increases when combined with coronary heart disease and chronic kidney disease. On the other hand, the comorbidity increases the risk of bleeding. Older age is also the risk factor of thrombotic and hemorrhagic complications. As a consequence, the choice of specific anticoagulant should be based on a solid evidences, obtained both from randomized clinical trials and from daily clinical practice. In the ROCKET AF trail the direct oral anticoagulant rivaroxaban showed a tendency to reduce the risk of thromboembolism by 20% compared with warfarin in the patients aged 75 years and older. The safety of rivaroxaban has been evaluated in the XANTUS POOLED program. According to the follow-up results for 12 months, more than 96% of patients didn't have any adverse event, and the number of patients with major bleeding was 1.5%. Several meta-analyzes reported a reduction of cardiovascular complications in patients treated by rivaroxaban. In the ROCKET AF trail, a “renal” dose of rivaroxaban (15 mg OD) was studied in patients with chronic kidney disease. The efficacy and safety of rivaroxaban were validated in this patients, and a simple algorithm for selecting the dose of this drug in patients with chronic kidney disease was provided.

 

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