Rational Pharmacotherapy in Cardiology

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Vol 10, No 2 (2014)
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134-146 664

Aim. To estimate incidence rate of first myocardial infarction (MI) with different outcomes and factors, it is influenced by, depending on the intensity of preventive measures in a population of middle-aged men during 15-year follow-up; to evaluate economic efficiency of primary medical prevention.

Material and methods. Two populations of middle-aged men with a total of 6656 males (3488 men the group of active prevention and 3168 the group of comparison) were followed up over 15 years.

Results. The group of active prevention revealed 22.1% reduced MI incidence rate during 5-year follow-up as compared to the second group, fatal MI incidence rate was 42.4% lower, p<0.05. Mortality rate in new cases of MI was 35.8% in the group of active prevention and 48.5% at routine treatment (p<0.05). The group of active prevention continued to have 17.9% reduced MI incidence rate during the 10-year follow-up as compared to the group of routine management (p>0.05), while patients with clinical signs of ischemic heart disease (IHD) and no history of previous MI kept significant distinctions in first MI incidence rate (41% less in the first group, p<0.05). First MI incidence for the 10-year period was the least at risk factors (RF) absence and twice higher even at single RF presence. Combination of RF caused 4-5 fold increase in risk for MI. Life status of 81.3% of the enrolled men (5410 of 6656) followed over 15 years was received along with the monitoring of prognosis.

Such indices as “life years saved” (LYS) and “quality-adjusted life years saved” (QALYS) for 1000 persons in the active prevention group were 53 and 51 years, respectively during the 5-year follow-up, 147 and 143 years – during the 10-year follow-up. In the long-term actual expenses for 1 LYS were 3.4-fold less than annual gross domestic product (GDP) value, at that charges for primary prevention – 4-fold less, which has been for the first time demonstrated using factual data and not mathematic modeling usually used in scientific literature.

Conclusion. The long-term prospective follow-up has demonstrated that the risk of first MI can be reduced by means of active and systematic prevention. Cost-effectiveness of primary prevention, including the one of MI, has been conclusively showed. The results allowed to validate the reasonability of active multifactorial prevention in the settings of primary healthcare, which makes it possible to define scientific-based recommendations for real practice.

147-152 598

Aim. To assess the potential of ursodeoxycholic acid (UDCA) in the prevention of liver dysfunction in patients with cardiovascular diseases (CVD) and high risk of cardiovascular events (CVE) with indications for statins use.

Material and methods. Patients (n=262, age 60.1±8.9 years) took statins for secondary prevention of CVE in observational cohort study. The follow-up duration was 6 months. UDCA was recommended for all patients because of liver diseases and/or biliary tract. Some of the patients with high treatment compliance strictly followed recommendations to take UDCA, and another part of the patients with low treatment compliance did not take UDCA. Comparison of these groups allowed highlighting UDCA effects.

Results. Controlled lipid-lowering therapy in combination with UDCA resulted in a significant reduction in total cholesterol (TC) and low density lipoprotein cholesterol levels after 6 months of follow-up to 4.3 mmol/L and 2.3 mmol/L, respectively (p<0.001). Deterioration in the dynamics of alanine-aminotransferase (ALT), aspartate aminotransferase (AST), creatinphosphokinase (CPK) and gamma glutamine transferase (GGT), as well as increase in serum bilirubin was not found. Moreover, in general significant decrease in ALT, AST, GGT and alkaline phosphatase (p<0.001) was observed, the levels of total serum bilirubin and CPK did not change at the end of the study (p=0.65 and p=0.16, respectively). Taking UDCA simultaneously with statins led to additional reduction in TC and low density cholesterol compared with statin monotherapy (p=0.01).

Conclusion. One of the affordable and effective ways to deal with a wider statin use in patients with liver and biliary tract disorders is their co-administration with UDCA.

153-159 638

Aim. To study the prevalence of hyperuricemia in the Russian regions, depending on the climatic, geographical, socio-demographic characteristics and some cardiometabolic risk factors.

Material and methods. Data from the ESSE-RF study from 10 regions of theRussian Federationare presented. All study participants were examined according to a uniform protocol. Measurements were standardized, biochemical tests were carried out in three Federal centers using the same methodology. The study was approved by independent Ethics committees, and all participants signed informed consent.

Results. The prevalence of hyperuricemia was 16.8% (25.3% in men and 11.3% in women; p<0.0001). Hyperuricemia incidence increases with age, does not depend on education, significantly associates with place of residence, elevated blood pressure, obesity and abdominal obesity, alcohol consumption and diuretics taking. After adjustment for all factors included in the regression analysis, prevalence of hyperuricemia in the Ivanovo Region is 1.4 times higher than this in the reference region (Tyumen), while prevalence of hyperuricemia in the Samara Region and theRepublicofNorth Ossetia-Alaniais 30% and 40 % lower.

Conclusion. Prevalence of hyperuricemia inRussiais defined; regions with the highest and lowest prevalence are identified. Associations of hyperuricemia with some social and demographic characteristics as well as cardiovascular risk factors are revealed.

160-165 451

Aim. To study the change of local myocardial contractility in patients with ischemic heart disease (IHD) and paroxysmal atrial fibrillation (AF) during treatment with amiodarone 200 mg daily compared with bisoprolol therapy 5 mg daily.

Material and methods. A total of 47 IHD patients with persistent AF were enrolled in the study. Sinus rhythm (SR) was restored during the first 24 hours after admission in all the patients. After SR restoration patients were randomly allocated into two groups receiving either amiodarone 200 mg/day during 6 months for SR maintenance (group 1) or bisoprolol 5 mg daily for ventricular rate (VR) control (group 2). To estimate a local myocardial systolic function all the patients were undergone steady-state radionuclide ventriculography in the first 24 hours after SR restoration and 6 months later.

Results. Sinus rhythm saving at amiodarone therapy within 6 months led to an improvement of the local myocardial contractility of the left ventricle with a significant increase in normokinesis zones from 79 (58.1%)  to 92 (67.6%), hypokinesis and akinesia zones reduction from 46 (33.8%)  to 41 (30.2%)  and from 11 (8.1%) to 3 (2.2%) (p<0.05), respectively. Achieving the target values of ventricular rate during the remaining episodes of AF in patients of group II did not significantly affect the local left ventricle contractility.

Conclusion. 6-month SR maintenance with amiodarone intake in IHD patients with persistent AF resulted in significant reduction of akinesia zones and increase in the number of normokinesia segments.

166-169 496

Aim. To assess the effectiveness of educational programs in the treatment of patients with metabolic syndrome (MS).

Material and methods. Patients with MS (n=68) were randomized into two groups of 34 people. Patients of the first group received standard antihypertensive therapy, while patients of the second group antihypertensive therapy and educational programs additionally. Examinations of carbohydrate, lipid and purine metabolism, blood pressure (BP) monitoring, anthropometric tests were performed before and after 24 weeks of therapy.

Results. Stable target BP levels [24 (70%) patients in Group 1 and 29 (85%) patients in Group 2] and improvement in metabolic parameters were achieved in patients of both groups. Besides in patients of the second group received additional trainings improvement of anthropometric indicators (decrease in waist circumference from 106±6.5 to 94±2.4 cmand body weight from 99±3.5 to 79±6.3 kg) was found.

Conclusion. The complex treatment of patients with MS should include educational programs in addition to antihypertensive drugs.


170-173 470

Aim. To study the effect of atrial fibrillation (AF) that existed before the myocardial infarction (MI), on near and long-term mortality in patients with acute MI.

Material and methods. The data of LIS register (Lyubertsy study on mortality rate in patients after MI), that included all patients hospitalized for acute MI (n=1133) during the period from 1 January 2005 to 31 December 2007, were used to solve the aim of the study.

Results. AF was recorded in 88 patients (7.8%), and the frequency of AF significantly increased with age. 22 patients with a history of AF (25%) died in hospital, and mortality in this group of patients was significantly higher than this in the whole group of patients (15.2%; p=0.025). However, these differences were not statistically significant when adjusted for age and gender (OR=1.25; 95% CI 0.77-2.04; p=0.37). 66 people from 961 patients, who were discharged from the hospital, had the AF before acute MI. Relative risk of death in patients with AF in this group (adjusted for age and sex) was significantly higher than this in patients without AF (OR=1.91; 95% CI 1.18-3.11; p=0.005). Conclusion. AF diagnosed in patients with acute MI at admission did not influence significantly hospital mortality. However, pre-existing AF increases significantly the risk of death in patients survived acute period of MI.


174-178 569

Aim. To assess prescribing structure, efficacy and safety of antithrombotic therapy in in-patients with permanent atrial fibrillation (AF).

Material and methods. Simple non-comparative retrospective descriptive one stage pharmacoepidemiological study was performed on the basis of analysis of 263 case histories of patients with permanent AF admitted to cardiology department of a general hospital.

Results. All patients were stratified into three groups depending on the value of the index CHA2DS2-VASc. Antithrombotic therapy was evaluated in each group. 1% patients (n=3) had minimal stroke probability, so there was no need for antithrombotic therapy. 6% (n=15) patients with AF had 1 point according to CHA2DS2-VASc scale. Acetylsalicylic acid was prescribed to 0.7% of cases (n=2), warfarin – to 5% (n=12). High risk of thromboembolic complications (CHA2DS2-VASc≥2) was revealed in 93% patients (n=245), 65% (n=172) of them received warfarin.

Conclusions. Antithrombotic therapy was administered for the vast majority of patients with AF (97.7%). Antiplatelet drugs were used in 25.4% of cases, including for patients with high risk of thromboembolic complications. Warfarin was prescribed in 70.3%. However, target level of hypocoagulation has been achieved in 51% patients only.

179-183 442

Atrial fibrillation is one of the main risk factor of ischemic stroke. Current problems of the management of patients with stroke due to non-valvular atrial fibrillation and secondary stroke prevention in these patients are considered. Data of own author’s observation for patients of this type during 6 months after discharge from the hospital are presented. The problems which patients faced with are analyzed. Comparative assessment of warfarin and dabigatran therapies is given.


184-189 425

Aim. To study an interrelation of anxiety and depression with arterial hypertension (HT) of various degrees taking into account gender distinctions.

Material and methods. One-stage (cardiology and psychometric screening) epidemiology study was carried out in 1% sample of the Novgorod Region adult population. The program of screening included the standard epidemiological record of HT detection and psychometric testing in 1607 respondents with the Hospital anxiety and depression scale (HADS). Risk calculation was performed by logistical regress model using disagreement criterion (odds ratio).

Results. HT prevalence rate was 52.1% among men and 49.8% among women of Novgorod Region. The highest prevalence rate of HT was observed at the age ≥70 years: 88.9% among women and 83.6% among men. Relationship between subclinical and clinical types of the anxiety, depression and HT degrees 2-3 was revealed with some gender peculiar properties. Patients with isolated systolic HT had high association with anxiety and depression irrespective of gender.

Conclusion. Revealed relationship between anxiety, depression and HT, especially in patients with HT degree 3, required an interdisciplinary approach to the therapy of this group of patients.

190-194 581

Aim. To evaluate clinical features of hyperphagia reactions, their significance in attraction abnormities within eating disorders and treatment options for these conditions with escitalopram.

Material and methods. Mental state of 39 women (age 19-50 years) with psychogenic overeating and obesity (body mass index of 30 to 53 kg/m2) was studied. Patients were admitted to the Institute of Nutrition of the Russian Academy of Medical Sciences. Diagnostic criteria for International Classification of Diseases, 10th edition, as well as Eating Disorder Inventory (EDI), Hospital Anxiety and Depression Scale (HADS) and Ferreri Anxiety Rating Diagram (FARD) were used for syndrome qualifications. Patient Global Impression of Change was also studied using a 4-point scale of results (excellent, good, fair, and negative).

Results. Clinical features of hyperphagic reactions were found. Escitalopram treatment course was completed with excellent and good results in 80% of patients. 50%-reduction in HADS score for anxiety was found in 74% of patients, for depression – in 63%, and for Ferreri scale – in 68% of patients. Escitalopram promoted more intensive body weight loss: 11% vs 8% of baseline weight in active and control groups, respectively. Adverse events occurred only in 7 (36%) patients; they were transient and did not require therapy discontinuation.

Conclusion: Significant differences of premanifest disorders were often observed in patients history. Escitalopram in these patients showed efficacy in improvement of both mental and somatic symptoms of anxiety. It decreased dependence on food as a factor mitigating affect and stress, thus provided better results in body weight reduction.


195-202 474

Part I (Diagnostics), was published in the journal “Rational Pharmacotherapy in Cardiology” 2014;10(1):62-72

Aim. To develop a comprehensive clinical and morphological approach to the nosological diagnosis and treatment of "idiopathic" arrhythmias (IA) and the syndrome of dilated cardiomyopathy (DCM).

Material and methods. Patients (n=320) with IA (n=190; 117 women, age 45.3±14.8 years) and DCM (n=130, 41 women, age 46.9±12.5 years) were included in the main group. 51 people (patients with ischemic heart disease; heart valve disease, hypertrophic cardiomyopathy, who underwent open-heart surgery; healthy volunteers) were included in the control group. Along with the standard tests evaluation of the level of anti-heart antibodies (185 patients with IA and 122 with DCM), viral serology (166 and 122), multispiral computed tomography (42 and 88), cardiac magnetic resonance imaging (41 and 22), coronary angiography (19 and 54), myocardial biopsy/autopsy (19/0 and 33/9) were performed.

Results. According to morphological study infectious-immune myocarditis was found in 78.9% patients with IA and 66.7% patients with DCM, arrhythmogenic right ventricular dysplasia in 5.3% and 4.8% of patients, respectively. Other genetic cardiomyopathies, including combination with myocarditis were revealed in other patients. The frequency of the viral genome detection in the myocardium in IA, DCM and the control group was 17.6%, 66.7% and 77.1%, respectively. However in the control group the incidence of myocarditis and anti-heart antibodies titers were significantly lower than in the main group, where a strong correlation between myocarditis and anti-heart antibodies titers was found. The algorithm of noninvasive nosological diagnostics was developed; it allowed to verify diagnosis in 95% of IA patients and 89% DCM patients

The basic therapy (antiviral drugs, corticosteroids, hydroxychloroquine, azathioprine) was performed in some patients with myocarditis. Improving of the antiarrhythmic effect of treatment in patients with IA, a significant increase in ejection fraction, a reducing of the size of the heart chambers and of pulmonary artery pressure in patients with DCM, a reducing of the need in surgical treatment (including in the virus-positive patients) occurred as results of treatment.

Conclusion. Nosological cause of IA and DCM syndrome can be diagnosed in most patients by using an integrated clinical and morphological approach. This allows managing effective etiotropic and pathogenetic treatment.

203-211 420

Aim. To study content of resident progenitor cardiomyocytes in endomyocardial biopsy samples of patients with dilated cardiomyopathy (DCM) and heart failure (HF) at different disease stages and relate it to patient clinical characteristics.

Material and methods. Resident progenitor cardiomyocytes were studied in endomyocardial biopsy samples from 14 patients (age from 26 to 52 years old) with DCM and HF by immunofluorescence method. Results were analyzed individually for each patient.

Results. Resident progenitor cardiomyocytes expressing simultaneously stem cell markers c-kit, MDR-1 and early cardiomyocyte differentiation markers GATA-4 and Nkx2.5 were found in endomyocardial biopsy samples from patients with DCM and HF. Resident progenitor cardiomyocytes detected by these cell markers were found in all patients at all disease stages.

Conclusion. Results show that the myocardial regenerative processes exist at all stages of the disease progression.


212-219 621

Arterial hypertension (HT) in patients with metabolic syndrome has features (early damage of target organ, a predisposition to thrombosis, refractory to standard antihypertensive therapy, high cardiovascular risk). The aim of HT treatment in patients with metabolic syndrome includes not only the achievement of target blood pressure, but also a reduction of target organ damage, correction of modifiable risk factors and associated clinical conditions. Results of multicenter studies on assessment of clinical efficacy of groups of antihypertensive drugs, their effects on metabolic parameters, the ability to prevent the development of cardiovascular events, diabetes mellitus, and renal dysfunction are presented.

220-230 453

Review of scientific evidences on contemporary concepts of the pathogenesis of mechanical dyssynchrony and its significance in patients with chronic heart failure is presented.

231-237 668

Chronic heart failure (CHF) is a major health problem in many countries now, and the cost of hospitalization is high. Early detection of atrial dysfunction, relationships between onset of symptoms and dysfunction of the atria, as well as their role in the development of systolic and diastolic heart failure is important. Interest in the assessment of left atrial transthoracic echocardiography with calculation of left atrial function index (LAFI) fraction and assessment of myocardial fibrosis with special software packages takes place lately. The search for ways to develop non-invasive methods for determining the fraction of atrial fibrosis and dysfunction is now underway. Detection of the most sensitive and specific methods will help to diagnose the initial manifestation of CHF and find an individualized approach to the treatment of each patient.


238-244 581

Up-to-date data on combination therapy of arterial hypertension in patients with chronic kidney disease are presented. Special attention is paid to the fixed combination of calcium antagonist lercanidipine and angiotensin-converting enzyme inhibitor enalapril.

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