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Rational Pharmacotherapy in Cardiology

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Vol 14, No 4 (2018)
View or download the full issue PDF (Russian)
https://doi.org/10.20996/1819-6446-2018-14-4

ORIGINAL STUDIES

474-487 242
Abstract

Aim. To describe the characteristics of the patient with MI who is admitted to a hospital and to characterize the main diagnostic and treatment interventions in clinic.

Material and methods. This study is observational and the part of big international project. It includes a representative sample of patients with MI admitted to 16 clinics in 13 regions of Russian Federation (Arkhangelsk region, Belgorod region, Bryansk region, Tver region, Saratov region, Rostov region, Samara region, the Republic of Tatarstan, Perm region, Tyumen region, Khanty-Mansiysk Autonomous district, Kemerovo region, Altai region). Patients were selected at random from among those experiencing a MI that were alive on the next morning after hospitalization. Enrollment took place from June 2015 to August 2016.

Results. Of 1,128 patients included in the study, 872 were male (77.3%) and 256 females. 21.4% of patients had a previous MI, 8.3% had undergone PCI, and 2.2% CABG. Turning to cardiovascular risk factors, 46.2% of patients smoked prior to hospitalization, 34.6% were obese and 52.1% had a high cholesterol level. Only 40.0% of patients had no contact with the health care system within 12 months before the MI. Every fourth patient (25.1%) had undergone dispensarisation within 12 months before MI, women significantly often than men (33.5% and 22.6%, p<0.001). Initial revascularization was performed in 73.2% of patients, PCI was the initial revascularization attempt in 49.4% of patients, and PCI with stenting in 46.7%.

Conclusion. Patient with a MI in Russian clinics is likely to have had a history of cardiovascular disease, and to have regular contact with the health care system within 12 months before the development of cardiovascular event. We demonstrated the high rates of appropriate MI treatment, without significant gender and age difference (except for thrombolysis), however, there is a reserve for increasing the proportion of patients who are undergoing revascularization.

488-493 136
Abstract

Background. The search for genetic predictors of stroke development is actively studied in all developed countries due to the need to address the primary prevention of socially significant diseases. Gene CYP17A1 is one of the many genes that can participate in the formation of predisposition to the development of stroke.

Aim. To examine association of the single nucleotide polymorphisms rs1004467 CYP17A1 gene with the development of stroke.

Material and methods. The study included 184 patients with stroke (active group; 113 men and 71 women; mean age 55.06±9.40 years), 131 of them with ischemic stroke and 41 with hemorrhagic stroke. The comparison group included 251 people with hypertension without stroke (160 men and 91 women; mean age 59.21±6.62 years) and control group – 157 persons without cardiovascular diseases (106 men and 51 women; mean age 54.94±6.64 years). Study participants underwent clinical (collection of complaints, anamnesis, physical examination), laboratory (blood chemistry, lipid profile) and instrumental (computer tomography of the brain, ultrasound duplex scanning of extraand intracranial blood vessels, electrocardiography, echocardioscopy) examination to verify the diagnosis, molecular genetic study of gene polymorphism СУР17А.

Results. The study established the association of homozygous genotype AA rs1004467 CYP17A1 gene with the risk of stroke, which is confirmed bya statistically significant increase in the number of carriers of homozygous genotype AA in the common allele rs1004467 CYP17A1 gene in patients of the main group (73.4±3.3%) compared to the control group (61.8±3.9%; p=0.03). Statistically significant increase in the number of carriers of genotype AA rs1004467 of CYP17A1 gene in patients with hemorrhagic stroke (70.7±7.1%) compared with the control (61.8±3.9%; p=0.01) was revealed. There are no statistically significant associations between the rs1004467 genotypes of CYP17A1 gene and the risk factors of stroke (hypercholesterinemia, burdened hereditary, hypertension, increased intima-media thickness of brachiocephalic arteries).

Conclusions. The ability to consider the genetic determinants of brain stroke allows to identify proactively the risk factors of this complex cascade process. Studies of gene polymorphism as a factor of genetic predisposition to various human diseases allow to determine the individual possibilities of optimal therapy for each patient, considering the identified risk factors.

494-500 116
Abstract

Aim. To study data on prehospital thrombolytic therapy in ST elevation myocardial infarction (STEMI) in the Perm Krai, its efficacy and safety.

Material and methods. The retrospective analysis using the official statistics and medical records of the emergency medical service, primary vascular department and regional vascular center for 2014-2017 was performed. Patients with a history of myocardial infarction in the period from 2015 to the 1st quarter of 2017 were included into the study. Medical records of 65 people with STEMI were studied. Patients were divided into two groups: Group I (n=27) – STEMI with thrombolytic therapy with recombinant staphylokinase; Group II (n=38) – STEMI with thrombolytic therapy with tenecteplase. Indirect signs of the efficacy of thrombolytic therapy, the degree of restoration of blood flow in the infarct-related artery according to coronary angiography, and the development of complications were analyzed. Data on general clinical and echocardiographic studies were collected. A telephone survey of patients was conducted to assess the long-term outcomes at the second stage.

Results. Increase in the number of prehospital thrombolytic therapy for acute coronary syndrome with ST elevation for 2014-2017 was found according to medical reports. A change in the proportion of the shares of prehospital thrombolytic therapy and percutaneous coronary intervention was also found. Recombinant staphylokinase was comparable to tenecteplase in efficacy and safety in STEMI patients in the first 12 hours. Large bleeding occurred in 1 (3.7%) case with recombinant staphylokinase and in 2 (5.3%) cases with tenecteplase. The number of life-threatening reperfusion arrhythmias was also comparable: 1 patient per each Group. Telephone contact was established with 21 (77.8%) and 30 (78.9%) patients in Groups, respectively. Relapse of angina was found among the interviewed patients in 3 and 5 cases in Groups, and decompensation of heart failure in 2 patients from Group I, 1 patient in each Group underwent coronary bypass surgery.

Conclusion. The accumulation and processing of data on the efficacy and safety of thrombolytic therapy with recombinant staphylokinase and tenecteplase is clinically justified.

501-508 180
Abstract

Background. Anticoagulants (AC) are the high-risk drugs. Their safety closely depends on physician’s compliance with clinical practice guidelines (CPG) and summary of product characteristics (SmPC).

Aim. To analyze the physician’s compliance with CPG and SmPC for AC prescribing for patients with atrial fibrillation (AF) and deep vein thrombosis (DVT).

Material and methods. The study comprised a retrospective review of electronic medical records (EMR) for 50 patients with AF and 50 patients with DVT admitted to general hospital in Moscow during the 2016-2017 period. Via clinical decision support system (CDSS) actual AC prescriptions in EMR were compared with recommendations from relevant CPG and SmPC to analyze deviations in AC indications/contraindications and dosing.

Results. ACs were prescribed for 43 (86%) AF patients, including warfarin (39.5%), direct oral anticoagulants (DOAC) (46.5%) and low-molecular weight heparin (LMWH) (14%). The structure of AC in-hospital therapy for DVT patients (excluding initial therapy) was the following: 39.5% DOAC, 33.5% LMWH and 27% warfarin. The cumulative rate of physician’s compliance with AC prescribing recommendations for AF/DVT patients was 88%. The rate of adverse drug events (ADE) in «non-adherent» group was significantly higher than in «adherent» one (34% vs 11%, respectively, OR=3.9; 95%CI 0.9-15.3; p=0.045). Cumulative compliance with AC dosing recommendations was 63.5 %. In «non-adherent» group direct cost for inpatient AC therapy was significantly higher than in «adherent» group 4041 rubles (interquartile range, IQR=7501 rubles) vs 1134 rubles (IQR=5911 rubles), respectively; p=0.02.

Conclusion. Physician’s noncompliance with CPG and SmPC can increase the risk of ADE and direct costs of AC therapy. The CDSS can be a useful tool both for clinical audit and for improving physician’s adherence to recommended AC therapy.

509-514 116
Abstract

Background. The study of the incidence of risk factors (RF) of stroke for primary and secondary prevention of this disease remains relevant. There are modifiable and non-modifiable RF.

Aim. To study the frequency of the main RF in patients with ischemic and hemorrhagic stroke in the urban population of Krasnoyarsk (Eastern Siberia).

Material and methods. Examination of 124 patients with an ischemic stroke and 28 with hemorrhagic was performed. Patients received treatment in neurologic center of Krasnoyarsk in 2014 year. The main criterion of inclusion was the confirmed diagnosis of an ischemic or hemorrhagic stroke. All patient had the clinic-tool and neurovisualizing examination and collecting the individual and family anamnesis with examination of modifiable and non-modifiable RF. The research of the neurologic status at patients both with ischemic, and with a hemorrhagic stroke was conducted by the standard technique. Based on results of computer or magnetic resonance imaging of a brain the diagnosis of an ischemic or hemorrhagic stroke was established.

Results. A distinctive feature of patients with hemorrhagic stroke was the occurrence of a vascular accident in younger age (6 years earlier) in comparison with ischemic stroke. Among patients with ischemic stroke elevated body mass index (BMI) was in 87 (70.2%) patients, burdened heredity was in 8.1% of cases, and 43.5% of patients were smokers. Among patients with hemorrhagic stroke 16 (57.1%) patients had elevated BMI. People with burdened heredity were not identified among them. Smoking was found in 22 (78.6%) patients in this group.

Conclusion. Improvement of treatment and prevention of an ischemic stroke are in many respects connected with clarification of RF and pathogenic mechanisms of its development. The rational pharmacotherapy directed to pointed impact on individual RF can reduce the risk of development of stroke not only at individual, but also at the population level.

NOTES FROM PRACTICE

515-523 174
Abstract

The growing population of elderly people is the main «antithrombotic drugs consumer» because there is higher prevalence of thromboembolic diseases (acute coronary syndrome, venous thromboembolism, atrial fibrillation) among them than among younger people. Elderly people have high risks of both thromboembolic and bleeding complications associated with antithrombotic drugs using. Antithrombotic drug choice is based on individual careful estimation of the «risk/benefit» ratio. Sometimes real clinical practice gives us problems and questions, having no answers in any guidelines. Such a difficult clinical case of elderly patient management is presented in this article.

524-528 148
Abstract

In recent years, there has been a clear trend towards an increase in the number of elderly patients suffering from several polymorbid diseases, which considerably complicates the forecast and tactics of management. A clinical case of an elderly patient, suffering for a long time from type 2 diabetes mellitus, receiving insulin and treated with programmed hemodialysis due to terminal chronic renal failure, and suffering from atrial fibrillation in permanent form, is presented. The patient was hospitalized in theCityClinicalHospital№1 named after N.I. Pirogov due to acute repeated myocardial infarction. An emergency percutaneous coronary intervention was performed, the infarct-dependent artery was stented with a drug-eluted stent. The postoperative period complicated by the development of acute blood loss associated with bleeding from the upper sections of the gastrointestinal tract, and severe anemia of the combined genesis (posthemorrhagic, renal). This situation required doctors to make non-standard decisions in the choice of antithrombotic therapy. This clinical case illustrates the difficulties in elderly polymorbid patient management in real clinical practice and the controversial issues arising in the prescribing the antithrombotic therapy, especially after bleeding had developed. The supporting guidelines cannot answer all the questions which the daily practice poses to the doctor. In each case, the resumption of antithrombotic therapy and its optimal choice for an elderly polymorbid patient with developed bleeding is the subject of discussion and presented a real challenge for the treating physician.

ASSOCIATED PROBLEMS OF CARDIOLOGY

529-536 166
Abstract

Statins are now widely used drugs for the treatment of dyslipidemia, effective drugs for lowering the level of low-density lipoprotein cholesterol, and also for reducing the risk of cardiovascular and cerebrovascular events. It is believed that statins are well tolerated. However, the potential relationship between statins and cognitive impairment in some people is assumed. This review paper was written in the light of the search for information on a specific problem of the potential adverse effects of statins on the cognitive function. The purpose of the article is to seek advice for health professionals on monitoring and reducing the risk of potential cognitive impairment during statin therapy. Rosuvastatin may be safer amongst statins in terms of influencing cognitive function. Evaluation of cognitive dysfunction in patients before starting therapy with statins is not necessary. Therapy with statins is not accompanied by a risk of developing cognitive dysfunction according to cohort and randomized studies. The presence of cognitive dysfunction and the exclusion of other possible causes of it, as well as the evaluation of the benefit/risk ratio for the abolition of statin therapy, are necessary in detecting cognitive dysfunction during statin therapy. A decrease in the dose of statin or the cessation of its use to assess the reversibility of symptoms is possible on the basis of the individual characteristics of the patient. Alternative replacement for another inhibitor of HMG-CoA reductase should occur if the statin is discontinued. A drug that less penetrates the blood-brain barrier, for example rosuvastatin, is more preferable.

537-542 73
Abstract

Material and methods. 55 patients with VLC class А, B, C according to Сhild-Pugh were examined. The average age of patients 42 years, disease duration – 3,8 years. Depending on the presence of ascites, patients were divided into 2 groups: 28 patients had no ascites (group 1), 27 patients had ascites (group 2), and a control group of 22 healthy people. Echocardiography was performed by the "VIVID E 95" device. All patients were evaluated diastolic function of the LV in accordance with the АSЕ/ЕAЕ-2009 and ASE/EACVI-2016 recommendations. Holter monitoring of ECG was performed. Statistical data processing was carried out using Statistica 6.0 statistical software package and Mann-Whitney nonparametric test. The correlation analysis was performed using the Spearman coefficient.

Results. In all patients there was an increase in the index of myocardial mass and relative wall thickness of LV in comparison with the control group, more severe disorders were identified in patients with VLC with ascites, p<0.001. In the study of LV remodeling, concentric hypertrophy was most common in patients with VLC – in 11 (43%) patients of the 1st group and in 19 (70%) patients of the 2nd group. Holter monitoring of ECG revealed supraventricular extrasystoles in 9 (32%) patients of the 1st group and 11 (40%) – 2nd group; paroxysmal form of atrial fibrillation – in 2 (7%) patients and in 5 (18%), respectively. It was found that the maximum index of the left atrial volume was higher in patients with VLC compared to control, and in patients with ascites this disorder was more pronounced (p<0.001). In accordance with the ASE/EACVI-2016 algorithm, normal diastolic LV function was registered almost twice as often as when using the ASE/EAE-2009 algorithm. Undefined result was recorded in 8% of cases due to tricuspid regurgitation.

Conclusion. Thus, patients with VLC develop an increase in the LV myocardial mass with the formation of concentric hypertrophy, remodeling of the left atrium with the occurrence of cardiac arrhythmias, diastolic LV dysfunction, and these changes are more pronounced in patients with ascites. In accordance with the new algorithm ASE/EACVI-2016 for detection of diastolic LV dysfunction, normal LV diastolic function was almost 2 times more common in patients with VLC than in accordance with the old ASE/EAE-2009 algorithm.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

543-551 139
Abstract

Aim. To study the effect of obesity in childhood and adulthood on the indices of arterial stiffness, central aortic pressure in the population sample of men 42 to 43 years.

Methods. The study is part of a 32-year prospective cohort monitoring of males, beginning with childhood (11-12 years). 303 (30.1%) of the representatives of the initial population sample (n=1005) were examined after 32 years. 290 people are included into the analysis. The average age of men at the time of the examination was 42.9 years. The study included a survey on a standard questionnaire, measurement of anthropometric indicators, blood pressure (BP), pulse counting. The stiffness of the arterial wall and central pressure was measured by the applanation tonometry.

Results. Normal body weight was found in 95 of 290 men (32.8%) at the age of 43 years, weight gain – in 111 (38.3%) and obesity – in 84 (28.9%). Men with obesity and overweight in adulthood had a statistically significant increase in body weight as early as in childhood. Central aortic BP (CBP), as a surrogate vascular rigidity index, was statistically significantly higher in obesity and overweight groups. A statistically significant positive relationship between the indicators characterizing childhood obesity (the Quetelet index, the thickness of skin folds), and the level of blood pressure in childhood was found in the correlation analysis. A positive correlation between the thickness of skin folds in childhood with CBP in adulthood, as well as a weak positive relationship between peripheral systolic BP (pSBP) in childhood and central systolic BP (cSBP) in adulthood have been found. From potential predictors evaluated at the age of 12 years and included in the regression model only the thickness of the skin fold under the scapula

affected cSBP at the age of 43. The increase in the thickness of skin fold under the scapula in childhood at1 mmis associated with an increase in сSBP by0.4 mmHg in the adult state. Among the predictors evaluated in adulthood, pSBP, peripheral diastolic BP (pDBP), and the Quetelet index have a statistically significant effect on the level of cSBP. The thickness of the skin fold on the abdomen at the age of 12 influenced central diastolic BP (cDBP) level at the age of43. Astatistically significant effect on the cDBP level was provided by pDBP, obesity rates among potential predictors evaluated in adulthood.

Conclusion. Central aortic pressure in adulthood is maximally dependent on increased peripheral blood pressure and obesity. Only obesity was important among children's predictors (12 years of age).

552-557 129
Abstract

Material and methods. In the cross-sectional population-based study of general unorganized population of Tomsk aged 25-64 years ultrasound screening examination of the carotid arteries was done for detection of atherosclerotic plaques (plaque). As potential plaque determinants the following factors were studied: age, gender, smoking, low and high density lipoproteins (LDL-C and HDL-C), triglycerides, arterial hypertension, body mass index (BMI), low educational status (LES), high-sensitive C-reactive protein, glucose, diabetes mellitus, antihypertensive and hypolipidemic therapy. Study of relationships was carried out with logistic regression analysis. The error probability of less than 5% was considered statistically significant.

Results. In the crude analysis most of the determinants under study showed statistically significant relationship with plaque presence. After adjustment for age and sex, LDL-C, smoking and LES were associated with CAS prevalence. In multivariable regression analysis 9 risk factors appeared to be independently associated with plaque presence, wherein age, male sex, LDL-C, BMI and HDL-C were the most significant. In the participants of 50 years and older the smoking effect was the next in significance after LDL-C.

Conclusion. The results obtained focus attention on the comparative value of the major atherogenic risk factors and suggest that currently effective and timely control of LDL-C is of primary importance for prevention of carotid atherosclerosis in the general working-age population. As well the findings of the study evidence that at the population level smoking is still one of the leading atherogenic risk factors.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

558-566 122
Abstract

A competent choice of drug therapy in a specific clinical situation is a difficult and important task that a practical doctor must regularly solve in everyday practice, and the consequences of errors in this decision can be quite serious. Therefore, evaluation of the quality of the prescribed therapy is extremely important.

In the treatment of cardiovascular diseases, medicines that have a proven effect on the outcomes of the disease, primarily on mortality rates (so-called "life-saving drugs") acquire special significance. There are several classes of such drugs, and in different situations, their positive impact on the prognosis of the disease may be different. On the other hand, one should remember the so-called "drug-related problems" (DRP), which include contraindications to the prescription of certain drugs in a particular patient, the possibility of developing side effects of drug therapy, aggravated by polypharmacy, inter-drug interaction, improper dosage of drugs, etc.

In this publication, an attempt is made to identify the main components by which the quality of the prescribed therapy can be evaluated in the treatment of cardiovascular diseases: compliance of prescriptions with official instructions for preparations, modern clinical guidelines, adequate selection of a specific drug within the class, drug formulation, salt of the drug, evaluation of important safety parameters and efficacy of the prescribed drug. In addition, a review of the methods and scales of the composite evaluation of the quality of drug therapy developed to date has been conducted, as well as attempts to improve them and create new ones that continue to the present day. Nevertheless, none of the currently known methods for assessing the quality of therapy is not universal or devoid of shortcomings.

Most likely, a universal method of assessing the quality of the prescribed treatment may not exist. In its most general form, it can be said that treatment should be based on modern evidence-based medicine, which is usually reflected in the clinical guidelines, without contradicting the official instruction on the use of the drug, considering the presence of concomitant diseases, that are often the reasons of contraindications to prescribing those or other medicines.

INNOVATIVE CARDIOLOGY

567-574 198
Abstract

The role of gut microbiota in the pathogenesis of cardiovascular diseases (CVD) and metabolic syndrome has attracted massive attention in the past decade. Accumulating evidence has revealed that the metabolic potential of gut microbiota can be identified as a contributing factor in the development of atherosclerosis, hypertension, heart failure, obesity, diabetes mellitus. The gut-host interaction occurs through many pathways including trimethylamine-N-oxide pathway (TMAO), short-chain fatty acids and second bile acids pathways. TMAO (the hepatic oxidation product of the microbial metabolite of trimethylamine) enhances platelet hyperreactivity and thrombosis risk and predicts major adverse cardiovascular events. Short-chain fatty acids and second bile acids, which are produced with the help of microbiota, can modulate host lipid metabolism as well as carbohydrate metabolism through several receptors such as G-protein-coupled receptors 41,43, farnesoid X-receptor, Takeda-G-protein-receptor-5. This way microbiota can impact host lipid levels, processes of weight gain, insulin sensitivity. Besides these metabolism-dependent pathways, there are some other pathways, which link microbiota and the pathogenesis of CVD. For example, lipopolysaccharide, the major component of the outer bacterial membrane, causes metabolic endotoxemia and low-grade systemic inflammation and contribute this way to obesity and progression of heart failure and atherosclerosis. This review aims to illustrate the complex interplay between microbiota, their metabolites, and the development and progression of CVD and metabolic syndrome. It is also discussed how modulating of gut microbiota composition and function through diet, prebiotics, probiotics and fecal microbiota transplantation can become a novel therapeutic and preventative target for CVD and metabolic syndrome. Many questions remain unresolved in this field and undoubtedly further studies are needed.

POINT OF VIEW

575-582 120
Abstract

The possibility of rivaroxaban using in elderly patients with non-valvular atrial fibrillation is discussed in the review. The results of ROCKET-AF randomized trial, including subgroup analysis in patients older than 75 years, are presented. The problem of unreasonable prescription of low doses of anticoagulants in real clinical practice and questions of adherence of patients to anticoagulant therapy are discussed. The results of two recent studies of actual clinical practice performed in patients over the age of 80 and 85 years, respectively, are presented as well as favorable profile of the efficacy and safety of rivaroxaban in these age groups. Rivaroxaban reduced the risk of stroke/systemic embolism by 38% and ischemic stroke by 41% with a comparable risk of major bleeding in patients older than 80 years. In another study, in patients older than 85 years in the rivaroxaban group, a 11% reduction in the risk of death from all causes, a reduction in the risk of major bleeding by 10% and an acute coronary syndrome by 14%, with similar risk of stroke/systemic embolism, clinically significant minor bleeding and a combined endpoint (stroke/systemic embolism, large bleeding, death from all causes) have been found.

583-590 100
Abstract

The issues of prevention of thromboembolic complications (TE) in the management of patients with atrial fibrillation (AF) are of leading importance. Recently, non-vitamin K antagonist oral anticoagulants (NOACs), previously known as new oral anticoagulants are used in the treatment and prevention of TE in patients with AF. A lot of data has been accumulated, in which the NOACs indications have been revised. As a result, the updating has been done in the Recommendations of European Society of Cardiology (2016), the project of Russian Society of Cardiology Guidelines (2017), as well as in the new Recommendations of the European Heart Rhythm Association (2018). At the same time, the issues of prevention ща hemorrhagic complications, especially gastrointestinal bleeding, remain unresolved. Currently, there are no clinical guidelines on the use of NOACs from the standpoint of prevention of gastrointestinal bleeding, as well as definition of the risk of gastrointestinal bleeding in the treatment of NOACs. The authors analyze the recommended algorithms for the evaluation of the risk of gastrointestinal bleeding in NOACs using.

591-597 123
Abstract

The metabolic syndrome is a highly prevalent condition associated with increased cardiovascular risk in the population. Microvasculature is the terminal part of the cardiovascular system which primarily reacts to the increased secretion of the pro inflammatory adipokines typical for the metabolic syndrome. Microcirculation and blood cell abnormalities are the leading mechanisms of cardiovascular events development in this condition. Prevalence of microcirculation abnormalities and red blood cell dysfunction in metabolic syndrome and their role in the increased blood viscosity and cardiovascular events development are covered by the paper. The microcirculation abnormalities with a special focus on red blood cell dysfunction (impaired aggregation, stiffness) seen in metabolic syndrome and associated conditions are discussed in detail. The impact of abnormal red blood cell deformability (secondary to cholesterol accumulation in the cellular membranes) on the hemorheological abnormalities is revealed. Abnormal red blood cell surface charge due to proinflammatory changes associated with insulin resistance in diabetes mellitus is highlighted. These abnormalities lead to increased red blood cell aggregation and plasma viscosity that are the essential components of cardiovascular events pathogenesis. Their timely diagnosis is crucial for effective cardiovascular prevention.

598-604 117
Abstract

Takotsubo syndrome (TTS) is a reversible left ventricular dysfunction characterized by local apical hypokinesia usually triggered by a physical or emotional stress. According to the last available data TTS may represent 2% of all admissions for acute coronary syndromes. Despite the reliable prevalence, diagnosis of TTS remains difficult. The initial presentation, both clinically and electrocardiographically, is similar to an acute myocardial infarction (AMI). The biomarker profile is also similar, although the peaks of troponin and creatinine kinase levels are lower, and brain natriuretic peptide levels are higher in patients with TTS compared with ST-segment elevation AMI. Modified Mayo diagnostic criteria are the most common for the diagnosis. Pathogenesis of TTS currently is not well understood. Catecholamines appear to play a central role in the pathophysiology of TTS. However, it is conceivable that some people have a genetic predisposition to stress-induced TTS. A genetic predisposition has been suggested based on the few familial TTS cases described. Despite reversible myocardial dysfunction, acute heart failure is the most common complication in the acute phase of TTS. In-hospital mortality rate is comparable to that of ST-segment elevation AMI. There are no randomized clinical trials to support specific treatment recommendations in TTS. It is believed that the tactics of managing patients with TTS hospitalized with suspicion of acute coronary syndrome should comply with the protocol of management of patients with AMI while acute coronary pathology is not excluded.

605-611 122
Abstract

Atrial fibrillation (AF) is the most common tachyarrhythmia complicating ST segment elevation myocardial infarction (STEMI), while ventricular arrhythmias (VA) can, not only be accompanied by a hemodynamic disorder, but in some cases, worsen its prognosis. The article presents a modern view on risk factors for development of AF (elderly age, left ventricle systolic dysfunction, heart failure, etc.), strategy and tactics of AF treatment in patients with STEMI, the indications for its pharmacological cardioversion and electro-impulse therapy. It is shown that I.V. administration of betablockers and in some cases amiodarone for reducing the frequency of ventricular contractions is advisable. Features and argumentative issues of triple antithrombotic therapy in patients with AF with STEMI, the possibilities and indications for the use of double antithrombotic therapy instead of triple one are described. Clinical significance and peculiarities of treatment of various types of VA have been determined, the role of myocardial revascularization, radiofrequency catheter ablation, normalization of electrolyte imbalance, use of beta-blockers and amiodarone in the prevention and therapy of lifethreatening ventricular arrhythmias has been emphasized. The irrationality, and sometimes the risk of carrying out prophylactic antiarrhythmic therapy for AF and VA in the acute stage of STEMI, as well as the role of the implantable cardioverter-defibrillator in primary prevention of death in certain groups of patients with low left ventricle ejection fraction after myocardial infarction was noted. The value of various antiarrhythmic drugs in their effect on the improvement of prognosis in patients after STEMI is estimated. The material is presented based on modern recommendations for the treatment of patients with STEMI, therapy of AF and VA, prevention of sudden cardiac death, as well as data from several controlled studies and own clinical experience of pharmacotherapy of arrhythmias.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

612-620 80
Abstract

The problem of the discrepancy between convincing evidences of the effectiveness of the use of mineralocorticoid receptor antagonists in patients with heart failure with reduced left ventricular ejection fraction and insufficiently frequent their use in clinical practice for the treatment of these patients is considered in the article. Experts opinions on the reasons for this discrepancy are also presented. New data on the effectiveness of the use of the mineralocorticoid receptor antagonist, eplerenone, in some clinical situations identified in the analysis of subgroups of participants in a large randomized clinical trial EMPHASIS-HF are discussed. The main goal of this study was to evaluate the efficacy of eplerenone compared with placebo in patients with heart failure and reduced left ventricular function. In addition, experimental animal studies, which may indicate the pleiotropic effects of eplerenone in patients with vascular diseases, are presented. The new data on the effectiveness of eplerenone in subgroups of patients with heart failure and certain characteristics may be an additional reason to draw the attention of physicians to the benefits of its use and, accordingly, its more frequent application in clinical practice for the treatment of patients with clear indications for this therapy.

621-628 164
Abstract

Aim. To summarize and systematize the information published in open sources on the development of various manifestations of liver damage in the use of the new oral anticoagulants (NOAC) for the registered indications and to analyze the published clinical cases of drug induced liver injury (DILI) development.

Material and methods. Search queries for keywords were made in the PubMed (MEDLINE), Scopus, Elibrary and Kiberleninka databases. The search query was composed of the name of the medicinal product (international non-proprietary and commercial name) or the common name of the group and words describing the different variants of the liver damage.

Results. As a result of the search 1497 articles were found. Duplicate articles, articles that do not match the review topic, and articles whose full-text version is not available were removed from the search results. Articles that do not describe specific clinical cases have also been excluded. The review includes 14 articles, published from 2007 to March 2018 in Russian and English and one article in French describing clinical cases of different types of hepatotoxicity in the application of NOAC.

Conclusions. Published clinical cases suggest that NOAC cause undesirable phenomena such as hepatotoxicity, the mechanism and frequency of which remain unclear.

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ISSN 1819-6446 (Print)
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