Rational Pharmacotherapy in Cardiology

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Vol 14, No 3 (2018)
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312-318 125

Heart rate (HR) acceleration is one of the risk factors of the number of prevalent chronic non-communicable diseases.

Aim. To evaluate changes in mean levels of HR in the Russian Federation (RF) and the United States of America (USA) in different age and sex groups from 1975 to 2014.

Material and methods. HR levels in men and women of different age groups were evaluated in the populations of the RF and the USA in 1975-1982 and in 2007-2014 by the secondary analysis of cross-sectional trials data. A total number of cases was 48974.

Results. In 80th years of XX century Russian men and women of all age groups had lower HR as compared to the USA, the distinctions were statistically significant in all age groups except for men aged 25-34 years (p<0.0001). During the next 3 decades HR significantly decreased in all groups of the USA population, while the RF population demonstrated variety of HR levels trends in different groups, absolute distinctions in mean values were relatively small and did not exceed 2 beats per minute. At the present time HR levels are less in the RF as compared to the USA in women aged 25-55 years and in men aged 25-34 years; in 55-64-year old men HR is somewhat higher in the RF than in the USA, other groups revealed statistically insignificant distinctions.

Conclusion. The USA evidently loosed out to the RF in mean levels of HR in all age groups 35 years earlier. During the next 3 decades situation has been worsened as applied to the RF and distinctions with the USA have been largely smoothed over. 

319-323 159

Aim. To study the changes in the stiffness of the arterial wall, vasomotor function of the endothelium, and appearance of new cases of atrial fibrillation (AF) in patients with arterial hypertension with long-term treatment with lisinopril.

Material and method. 66 hypertensive patients with cardiac sinus rhythm at the age of 48-64 years (mean age 58.4±4.2 years) were included into the study. They were randomized into 2 groups: patients of group 1 (n=35) were prescribed lisinopril or a combination of lisinopril with hydrochlorothiazide over the 5-year follow-up; patients of group 2 (control) did not receive angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. The follow-up duration was from September 2010 until June 2016. It included telephone calls once every 3 months and annual clinical, instrumental and laboratory examination. The new-onset AF was identified by the 24-hour Holter ECG monitoring results and by patient symptom diaries.

Results. New-onset AF was registered in 2 patients (6%) in the lisinopril group and in 4 patients (13%) from the control group (p=0.001) over the 5-year follow-up. Lisinopril significantly reduced AF incidence in hypertensive patients. The patients on lisinopril were found to have no significant changes in the left ventricular mass index and left atrial size according to echocardiography done after the 5-year follow-up whereas in the patients of control group both parameters increased significantly. Lisinopril contributed to the maintenance of endothelial vasodilator function and prevented increase in arterial wall stiffness.

Conclusion. Long term lisinopril treatment was found to significantly reduce the AF incidence in hypertensive patients over the 5-year follow-up. Lisinopril demonstrated organoprotective properties throughout the cardiovascular disease continuum and can be recommended for primary prevention of arrhythmia in hypertensive patients. 

324-329 125

The lethality of patients with acute myocardial infarction with ST-segment elevation (STEMI) depends on many factors. In conditions of timely transportation of the patient to the center of percutaneous coronary intervention one of these factors is the severity of the coronary bed lesion. In clinical practice, the most common method of assessing such lesions is the SYNTAX Score scale.

Aim. To study the impact of the assessment by angiographic SYNTAX Score scale on in-hospital complications and lethality in patients with STEMI.

Material and methods. The single-center observational retrospective study was performed. The medical data of 816 cases of treatment of patients with STEMI in the first 6 hours from the onset of symptoms were analyzed. All patients underwent reperfusion therapy (primary percutaneous coronary intervention or pharmacoinvasive strategy (FIS)) with assessment of the SYNTAX Score index prior to intervention. The main group (SYNTAX Score ≤22 points) and the comparison group (SYNTAX Score index >22 points) were comparable in terms of clinical characteristics and time delays.

Results. An increase in the SYNTAX Score more than 22 points was an independent predictor of hospital complications and lethality (4.9% for SYNTAX Score ≤22 points and 21.9% – for >22 points). The group with a high SYNTAX index was older, had a higher proportion of smokers (46.8% vs 36.1%, p=0.015) and patients with myocardial infarction history (38.5% vs 20.6%, p<0.001), fewer patients to whom the FIS was applied (33.3% vs 45.7%; p=0.017). Nevertheless, in multivariate analysis, the initial clinical data of patients influenced the hospital prognosis, first of all in patients with SYNTAX Score ≤22 points. The group with a more severe lesion of the coronary bed was represented by patients with frequent development of pulmonary edema, cardiogenic shock and ventricular fibrillation. Cardiac complications in this group of patients were less dependent on the initial characteristics. Strong SYNTAX Score correlations were found with left ventricular ejection fraction (r=-0.156, p<0.001), the number of implanted stents (r=0.226, p<0.001), and with complications and lethality. The frequency of hemorrhagic complications did not depend on the severity of the coronary bed lesion.

Conclusion. The use of the SYNTAX Score scale in clinical practice is scientifically grounded and advisable. Stratification of high-risk patients with STEMI during primary angiography based on the SYNTAX Score scale has a high prognostic value. 

330-336 152

Background. Digoxin takes important place in the management of patients with paroxysmal or persistent atrial fibrillation (AF). Monitoring of serum digoxin concentration (SDC) seems to be perspective way to improve the safety and efficacy of treatment. At the same time, there are no generally accepted reference ranges for SDC, especially in terms of the onset of therapy.

Aim. To evaluate the potential contribution of SDC monitoring in the context of efficacy of AF treatment with the use of digoxin in elderly patients.

Material and methods. A retrospective analysis of treatment of patients with recent-onset (n=91) or permanent (n=58) AF was performed. In all cases, the strategy of heart rate (HR) control was realized, including treatment with digoxin in 104 cases. SDC was measured twice during the digitalization: 20 hours after the first digoxin dose, and at the endpoint (time of sinus rhythm spontaneous restoration or, if the rhythm not restored, on day 7 of AF persistence).

Results. The influence of digoxin on HR was dose-dependent since the 1st week of therapy, and the SDC dynamics was strictly associated with change in HR (r=-0.66, p<0.001). There was a negative correlation between the probability of the sinus rhythm restoration due to digoxin therapy and the SDC: its probability in high SDC was significantly lower compared to other approaches to the HR control (0% vs 76% in beta-blocker monotherapy; and vs 100% in therapy with beta-blocker + lower-SDC, p=0.036). In patients with persisted AF and low SDC, the digoxin was withdrawn more often due to lack of clinical efficiency.

Conclusions. The SDC monitoring at the 1st week of digitalization could be used to improve the efficacy of therapy and to minimize the risks of spontaneous rhythm restoration, if not desired, and to reveal the disproportion between its high dose and low efficacy. The role of this diagnostic tool seems to be limited to safety control and negative predictive value for efficacy (the lower concentration, the higher risk of inefficiency), whereas its positive predictive value in terms of efficacy seems contradictory. The obtained data could be used for decision-making for recommendation of longterm digoxin usage if its contribution into HR control is doubtful. 

337-343 106

Aim. To study the relation of various factors with adherence to long-term drug therapy in patients with cardiovascular diseases in district hospital of small town in Saratov Region and patients from clinical hospital of Saratov medical university.

Material and methods. The hospitalized patients with cardiovascular diseases were included into the prospective study of long-term adherence to treatment. Questioning of patients with the determination of the attitude of respondents to their health, the desire to receive information about the disease, the level of awareness of the therapy, the degree of participation in the treatment process, the nature of the relationship with the attending physician was performed. A year after discharge, control calls were made to patients to learn whether the patient was continuing treatment prescribed a year ago in the hospital. The data on patient adherence in both hospitals were analyzed.

Results. 108 patients in the district hospital (58% of selected patients) and 70 in the Saratov hospital (33% of selected patients) responded to all questions in the questionnaire during hospitalization. Successful reaching by phone 12 months after discharge from the hospital took place in 74 patients of the small town and 40 patients of the regional center. The continuation of treatment was found in 28 (38%) and 24 (50%) patients, respectively. Patients who continued treatment significantly differed from those, who stopped therapy, by presence of myocardial infarction in anamnesis [14 (78%) patients in the university hospital and 6 (60%) patients in the district hospital; p<0.01] as well as acute cerebrovascular accident [6 (78%) patients in the university hospital and 4 (75%) patients in the district hospital; p<0.05] and stable angina class I-III [22 (61%) patients in Saratov and 28 (44%) patients in the small town; p<0.01]. Adherence to recommendations after 12 months was found in patients who considered that doctor or relatives were responsible for their health (6 patients in Saratov and 12 – in the small town; p<0.05) and believed that attending physician determines the portion of information provided to the patient [20 (60%) patients of the district hospital and 11 (63%) patients in the university clinic; p<0.05 for university clinic].

Conclusion. The adherence to long-term treatment after discharge remained low and did not exceed 50% among patients in both groups. The paternalistic model continued to dominate in the doctor-patient interconnection system.

344-349 97

Aim. To study the erythrocyte electric charge (EEC) in patients with metabolic syndrome (MS).

Material and methods. 112 patients (mean age 61.4±7.2 years) with MS (average duration of MS 8.7±5.2 years) were examined. Control group consisted of healthy volunteers (n=25) of similar age. The level of EEC was detected by the method of adsorption of a positive cationic dye (cationic blue O) on the surface of the erythrocyte plasma membrane up to the complete neutralization of their negative charge, followed by photometry of the solution and calculation of the number of charges on the erythrocyte cell surface. The results of the study were processed by Statistica 10.0 software.

Results. Hypertension was found in 73% of patients with MS, hyperglycemia – in 39%, diabetes – in 36%, dyslipidemia – in 80% of patients. The EEC in MS patients (1.59±0.05×107) was lower than this in the control group (1.65±0.03×107; p<0.05). With MS duration more than 5 years, the EEC was significantly lower in comparison with control group (p<0.05). In patients with obesity II-III degrees as well as dyslipidemia the EEC values were significantly lower vs control group (p<0.05). In patients with MS, a significant negative correlation of EEC with total cholesterol (r=-0.51, p<0.05) and triglycerides (r=-0.51, p<0.05) levels were revealed.

Conclusion. In patients with MS with increase in the MS duration, degree of obesity and lipid metabolism disorders, significantly lower values of EEC were observed. 


350-355 170
The article presents a clinical observation of the left atrial appendage thrombosis in a 51-year-old female patient with a paroxysmal form of nonvalvular atrial fibrillation which occurred despite long-term anticoagulant therapy with apixaban in a full dose (5 mg b.i.d.), and the patient’s management. The patient was admitted with recurrent symptomatic paroxysm for more than 48 hours, because of which, in accordance with the recommendations, transesophageal echocardiography was performed before an emergency rhythm restoration. Thrombus in the left atrial appendage 0.5×1.03 cm in size was detected. It was decided to refrain from the immediate restoration of the rhythm due to the very high risk of thromboembolic complications. In connection with the categorical refusal of the patient from warfarin, it was decided to replace apixaban with another direct oral anticoagulant – dabigatran 150 mg bid for a period of 4 weeks followed by performing a control transesophageal echocardiographic study. As a result, no thrombus was found on control echocardiography. The particularity of this observation is concomitant hypertrophic cardiomyopathy and diabetes mellitus type 1 in this patient.
356-360 119
Syndrome of hemodynamic depression is a frequent complication of the carotid artery endovascular intervention and, as a rule, is transient in nature. This article presents a clinical case of carotid artery stenting in a 63-year-old patient. The specific feature of this patient was the initial sinoatrial node dysfunction as a permanent sinus bradycardia. The examination verified multisite atherosclerosis, including coronary artery stenosis, manifested by the presence of stable angina, without history of myocardial infarction. Therefore, coronary endovascular treatment was firstly performed. Reexamination after coronary blood flow restoration revealed stable sinus bradycardia persistence without any positive or negative changes. According to anamnesis, examination and instrumental diagnostic results, indications for permanent cardiac pacing were not identified. Carotid artery stenting after the necessary preventive measures was successful. The article also considers possible risk factors of significant perioperative bradycardia during carotid angioplasty with stenting and measures preventing cardiac conduction perioperative worsening.
361-369 149
Acute myocardial infarction (AMI) is one of the main causes of morbidity and mortality, both in the Russian Federation and around the world. Approximately, in up to 10% of patients with clinical diagnostic features of AMI, early angiography does not reveal an occluded vessel or possibly any evidence of coronary artery disease. These patients constitute an intriguing subgroup referred to as “Myocardial Infarction with Non-Obstructive Coronary Arteries” (MINOCA). MINOCA is a collective concept that unites many different pathologies, which determines the essential heterogeneity of the etiological factors. Coronary artery embolism is recognized as an important non-atherosclerotic cause of AMI. In turn, the most common underlying disease in those with coronary embolism is the atrial fibrillation. The advantages of reperfusion strategy and cardioprotective therapy in the treatment of obstructive arteriosclerosis are well studied, widely presented in the literature and supported by a strong evidence base, while the issues of diagnosis and treatment of patients with MINOCA are currently widely discussed We present two clinical cases of embolic myocardial infarction in patients with atrial fibrillation, diagnosed in our clinic in 2017.
370-378 145
Hypertensive heart disease with biventricular cardiac failure is not common in clinical practice. This diagnosis requires an extensive diagnostic search. We present the clinical case of the male patient of 38 aged. He was admitted to the clinic with heart failure 3-4 NYHA class. EchoCG revealed symmetric hypertrophy of the left ventricle up to 18 mm without its dilatation, a decrease in ejection fraction up to 42%, restrictive hemodynamics, overload of the right chambers, severe pulmonary hypertension (60 mm Hg). The clinical status included persistent arterial hypertension (180-220 and 120-150 mm Hg), effusion in both pleural cavities and pericardium, ascites, renal failure. During examination (multispiral computed tomography, magnetic resonance imaging, scintigraphy with 131I-MIBG), bladder paraganglioma was diagnosed (normatenafrin 1468 μg/day). The resection of the tumor was performed, according to immunohistochemical research – neuroendocrine carcinoma, G1. After 3 months a partial regression of hypertension and cardiac failure was observed with the preservation of a high level of creatinine. The criteria and differential diagnosis of the hypertensive heart disease and the syndrome of primary myocardial hypertrophy, diagnostics of the urinary bladder paraganglioma, complex mechanisms of myocardial damage within the pheochromocytoma and its prognosis are discussed.


379-386 122
The paper aimed to present evidence of the effect of some pathophysiological features of chronic obstructive pulmonary disease (COPD) on cardiac remodeling in patients free of overt cardiovascular diseases, traditional cardiovascular risk factors and pulmonary hypertension. Contrary to traditional beliefs that cardiac abnormalities in COPD have been mainly associated with the right ventricle, several recent studies have shown an independent effect of pulmonary hyperinflation and emphysema on left ventricular (LV) diastolic filling and LV hypertrophy. Pulmonary hyperinflation and emphysema cause intrathoracic hypovolemia, low preload, small end-diastolic dimension and mechanical compression of LV chamber which could worsen end-diastolic stiffness. Interestingly, that the presence of LV hypertrophy in COPD patients is important but currently poorly understood area of investigation. Pulmonary hyperinflation, increased arterial stiffness and sympathetic activation may be associated with LV hypertrophy. Two-dimensional ultrasound speckle tracking studies have shown the presence of sub-clinical LV systolic dysfunction in patients even with moderate COPD and free of overt cardiovascular diseases. Sarcopenia related to the inflammatory-catabolic state in COPD and hypoxia could play an important role regarding LV systolic dysfunction. Recent data reported the effects of long-acting bronchodilators on reducing lung hyperinflation (inducing lung deflation). Further studies are required to evaluate the effects of pharmacological lung deflation therapy on cardiac volume and function.
387-392 113

Aim. To study the structural and functional parameters of the heart, as well as the effect of antiviral therapy on certain cardiohemodynamic parameters in patients with viral liver cirrhosis (VLC).

Material and methods. 96 patients with VLC (median age 42.1 [36;44] years, median duration of the disease – 3.5 [2.8;6.7] years) were examined. Patients without ascites (n=59) were included into the 1st group, and patients with ascites (n=37) – into the 2nd group. The control group included 21 healthy volunteers. Standard and tissue echocardiography, Holter monitoring of electrocardiogram were performed in all participants.

Results. Ventricular extrasystoles (class I to IVB) were found in 8 (13%) patients of the 1st group and in 12 (33%) patients in the 2nd group. The corrected interval of QT in the patients of the 1st group was 457.9 [442;468] msec, in the second group – 478 [433;502] msec, in control – 427.9 [406;438] msec (p<0.001). Supraventricular arrhythmias were represented by supraventricular extrasystoles in 15 (25%) patients of the 1st group and 18 (50%) – of the 2nd group; paroxysmal atrial fibrillation in 2 (3%) and 7 (19%) patients, respectively. The systolic velocity Sm of the lateral wall (3, 9 segments) in patients with ascites was lower by 23% and 25%, respectively, compared with the patients of the 1st group; Tei index increased in patients with ascites compared with the control group and the 1st group, p<0.001. In patients with VLC without ascites, the parameters characterizing the mass of the myocardium of the left ventricle increased, the left atrium and pulmonary artery widened. These disorders increased in patients with ascites; besides the systolic pressure in the pulmonary artery increased, and segmental and global systolic function of the left ventricle decreased. Antiviral therapy was accompanied by a decrease in the mass of the left ventricular myocardium, the index of left atrial volume and systolic pressure in the pulmonary artery.

Сonclusion. The increase in the myocardium mass of left ventricle, left atrium, pulmonary artery diameter, as well as cardiac arrhythmia and prolongation of the corrected QT interval were found in patients with VLC without ascites. These changes were more pronounced in patients with ascites, and additionally they increased pressure in the pulmonary artery and decreased systolic function of the ventricles of the heart. The antiviral therapy had a positive effect on some cardiohemodynamic parameters. 


393-401 234

Background. The prevalence of hypercholesterolemia (HCE) is quite high in the Russian Federation (RF), and it is associated with clinical consequences and with potential economic impact. Impact includes not only cost of its correction, but also the cost of treatment of diseases and complications, as well as the deficiency of the gross domestic product (GDP).

Aim. Evaluation of economic impact due to HCE in the Russian population, including direct expenditures of the Health Care System as well as nondirect impact in common economy.

Material and methods. Prevalence of HCE in the RF was identified based on local published studies. Local statistical data (2016) on cardio-vascular diseases (CVDs), including Ischemic Heart Disease (IHD), Myocardial Infarction and cerebral-vascular disease were included in the analysis. Population Attributive Risk (PAR) of HCE in CVDs has been extrapolated on all Russian population. Official statistics, parameters of Govern Guarantees Program of Free Medical Aid were used for modelling of direct and non-direct components of economic impact. Total amount of premature deaths with calculation of years of potential life lost until life expectation at 72 years was calculated. Economic impact due to premature CVDs mortality in economic activity age with consideration on ratio of employment have included GDP lost. Calculation of GDP lost also included monetary impact based on number of disability CVDs patients multiplied on GDP per capita in disability group.

Results. Visits to policlinics of patients with CVDs and HCE had a first place among all calls for medical aid. In the same time, hospitalization required in higher expenditures (outpatients cost treatment expenditures were 2.43 billion RUR, in-patients treatment – 18.21 billion RUR). IHD with HCE was most expensive for direct expenditures in comparison with other CVD groups: more than 28.9 billion RUR per year, and with direct non-medical expenditures of 29.3 billion RUR in total. Years of potential life lost in economic active age were one million in total, 1.29 trillion RUR per year mostly due to indirect expenditures due to premature deaths in economy activity age (99% of impact). Total Economic impact due to HCE in the Russian population for all HCE are estimated as 1.295 trillion RUR.

Conclusion. Total economic impact due to HCE in the RF is 1.5% of GDP (2016), 1.295 trillion RUR. Direct expenditures included Health Care System expenses; disability covering had 2.3% only. Main part of impact is economic lost due to premature mortality and decrease of labor productivity. HCE patients control at target levels with help of healthy lifestyle and adequate pharmaceutical therapy can decrease economic impact. 

402-407 108

Aim. To study the structure of medical prescriptions of antihypertensive agents for patients with arterial hypertension (HT) in the outpatient practice of Kursk (Russia) and Chisinau (Republic of Moldova).

Material and methods. The questioning of doctors of medical organizations in Kursk and Chisinau was carried out as a one-stage descriptive study from October 2015 to February 2016. The questionnaires included questions on the pharmacoepidemiological aspects of prescribing antihypertensive drugs. Total number of respondents was 218, of them – 106 (26 cardiologists and 80 therapists) in Kursk and 112 (28 cardiologists and 84 therapists) in Chisinau.

Results. In the real practice for HT treatment doctors in Kursk used more often beta-adrenoblockers (BAB), somewhat less often – angiotensinconverting enzyme (ACE) inhibitors, then diuretics. The shares of calcium channels blockers (CCB) and angiotensin II receptors blockers (ARB) were small – 8.8 and 5.2%, respectively. In Chisinau doctors gave preference to ACE inhibitors, then diuretics and BAB. Frequency of CCB prescriptions was almost identical to that of ARA – 13.7 and 13.6%, respectively. The additional antihypertensives, including central action drugs and alpha-adrenoblockers, were used rarely in both Chisinau and Kursk (1.3 and 1.6%, respectively). Doctors of Chisinau, when carrying out combined pharmacotherapy, gave priority to free combinations of antihypertensive drugs (64.4%), fixed combinations were used in 26.7% of cases. In Kursk, the ratio of these specified tactics of combined therapy was 53.5 and 34.1%, respectively. Among the pharmaceutical companies whose medicines were preferred by doctors in Kursk and in Chisinau, the leading positions were taken by KRKA (38.0 and 25.4%, respectively), Gideon Richter (13.5 and 28.7%, respectively) and Berlin-Chemie (26.7 and 15.6%, respectively).

Conclusion. ACE inhibitors, diuretics, BAB were priority classes in the prescribing antihypertensive drugs according to survey of doctors in Kursk and Chisinau. In the conditions of the existing pharmaceutical market of Chisinau doctors used ARB and CCB more often than doctors from Kursk. The main share of doctor’s prescriptions in Kursk and Chisinau, considered both for group of antihypertensive drugs, and for certain representatives of each group of drugs, corresponds to the current recommendations on the pharmacotherapy of patients with HT. 


408-417 177

Aim. To assess quality of life (QoL) and its dynamics during nicorandil treatment in patients with stable ischemic heart disease, to study the relationship of treatment adherence and QoL indicators when treated with nicorandil.

Material and methods. Observational program NIKEA included 590 patients with angina pectoris. Seattle Angina Questionnaire (SAQ) was used to assess QoL. Patients completed SAQ at the visit of inclusion (V0) and at the visit after 3 months of observation (V3). Potential and actual adherence to therapy was assessed by medical interviews at visits V0, V1 (1 month of observation) and V3. During the visit V0 417 people (from 590 ones enrolled into the study) completed SAQ (71% response); after 3 months (V3) SAQ was filled in by 454 of 552 people who came to this visit (82% response). According to the results of medical interviews, potential adherence (visit V0) was determined in all 590 patients, actual adherence to nicorandil (visits V1 and V3) was assessed in 552 patients who came to these visits. In accordance with the degree of adherence, all patients were divided into 3 groups: (1) adherent to treatment (taking nicorandil for the first three months), (2) non-adherent (who refused to take nicorandil), and (3) partially non-adherent (who started nicorandil, but for various reasons stopped taking the drug).

Results. In all patients, regardless of their adherence to the recommended drug, there was an increase in QoL according to all five scales of the SAQ after 3 months of follow-up. Statistically significant positive dynamics of all SAQ indicators was found only in adherent patients (p<0.0001 for all aspects). Patients, who showed good adherence to nicorandil at V1, had more severe angina at the beginning of treatment (according to “Angina Stability” and “Angina Frequency” indicators). These patients also had lower QoL “Disease Perception” score and more confidence in the doctor (“Treatment Satisfaction” score) than non-adherent patients (p<0.05). In non-adherent patients a mild degree of angina was determined 2 times more often according to “Angina Frequency” indicator (p=0.03).

Conclusion. The results of the study confirm the interrelation and mutual influence of the QoL indicators and treatment adherence to nicorandil. Effective treatment with nicorandil in patients with lower health-related QoL indicators could increase treatment adherence. On the other hand, the mild degree of angina, the low level of confidence in the treating doctor, the side effects of the new drug reduce medication adherence of patients, which, as a result, negatively affects the QoL of these patients


418-424 131
Approaches to personalized therapy based on practical work of physicians are discussed. Personalized treatment considers patient’s interests and position, mechanisms of symptoms, somatic and mental comorbidities, chrono medicine, environment, genetics, and prognosis. Personalized treatment may be more effective, safe and inexpensive in compare with of traditional standardized care based on randomized controlled trials and clinical practice guidelines. Limitations and weaknesses of medical guidelines of authoritative professional societies are also discussed. Recommendations of clinical guidelines are based on randomized controlled trials with strict selection of patients without severe comorbid diseases. Accordingly, trials and guidelines conclusions cannot be applied for patients with heavy comorbidity. This justifies the need for organizational solutions and computer programs for support personalized treatment of patients. It is important to develop institute of primary care physicians and to train specialists in field of comorbid somatic diseases and mental disorders.


425-433 154
The review focuses on the impairment of the carotid, coronary arteries and lower-extremity arterial disease. Systemic involvement of various vascular beds in atherogenesis is emphasized. Epidemiological characteristics of morbidity and mortality from the main clinical manifestations of atherosclerosis - ischemic stroke, ischemic heart disease and lower-extremity arterial disease are given. The current principles of drug therapy are considered from the point of view of improving the prognosis and eliminating ischemia. The basic positions of International and Russian clinical recommendations on the management of patients with the presence of certain clinical manifestations of atherosclerosis are discussed. Detailed administration schemes and the preferred doses of statins and antiplatelet agents depending on the localization of atherosclerotic lesion and the severity of stenosis are described. The target blood lipids levels in the treatment with statins are given. The advantages of statins as drugs that reduce the risk of cardiovascular complications are presented. Current data on the pattern of antiplatelet use, including acetylsalicylic acid, in individuals with clinical manifestations of atherosclerosis are given. The principal tactic of dual antiplatelet therapy and schemes of its use in patients undergoing percutaneous coronary intervention, coronary artery bypass surgery and in individuals with a history of acute coronary disorders are considered.
434-440 181
Cardiovascular diseases occupy a leading position in morbidity, mortality and disability in most countries. Ischemic heart disease and stroke lead in the structure of mortality from cardiovascular diseases. The issues of lipid-lowering therapy with statins in the aspect of stroke prevention are discussed in the article. The main risk factors of atherosclerosis and their prevalence are presented. Topical standards for statin use, evidence-based medicine data obtained in randomized clinical trials, and evidence from actual clinical practice are covered. Possible promising areas of statin use for the prevention of acute cerebrovascular accident are also considered. Combination therapy together with other lipid-lowering drugs, as well as drugs of other pharmacological groups, the use of statins from earlier ages, the practical implementation of pleiotropic effects of statins can be attributed to the latter. The authors clearly demonstrate that the actual practice of using statins lags significantly behind the ideal, reflected in the recommendations and randomized clinical trials. Adherence to medical recommendations is one of the key factors in this. The main factors that can influence the increase of adherence of patients to taking statins and increase the effectiveness of their application in real clinical practice are presented.
441-450 233
The choice of anticoagulant therapy in patients with atrial fibrillation (AF) and concomitant diseases – coronary heart disease (CHD), including acute coronary syndrome (ACS) in history, peripheral arterial disease (PAD), is discussed in the article. The overall mortality and incidence of myocardial infarction in patients with CHD and AF is higher than in patients with AF without CHD. Patients with AF and PAD compared to patients with AF without PAD have higher risks both stroke and systemic embolism. The prescription of triple antithrombotic therapy is necessary for patients with a combination of AF and CHD who underwent percutaneous coronary interventions (in ACS or elective surgery). The possibility of prescription and duration, the choice of specific drugs and their doses should be determined individually, based on the risks of ischemic events associated with stenting, the risk of ischemic stroke and bleeding. Use of new oral anticoagulants (NOAC) instead of vitamin K antagonists (eg, warfarin), low doses of NOAC, studied in trials and proven efficacy in the prevention of stroke/systemic embolism, the use of clopidogrel as a drug of choice from the P2Y12 inhibitor group, the use of low doses of acetylsalicylic acid (ASA), the routine administration of drugs from the proton pump inhibitor group is recommended to minimize the risk of bleeding. The data of subanalysis of the ARISTOTEL randomized clinical trial, indicating a high profile of efficacy and safety of apixaban in patients with AF, depending on the presence of CHD, PAD, concomitant use of ASA, are also presented in the article. The benefits of apixaban over warfarin for reducing the risk of stroke/systemic embolism, total mortality and the risk of bleeding in a subgroup of CHD patients are just as obvious as in the general population of the ARISTOTLE study, and in the subgroup of patients without CHD. Treatment with apixaban, both in the subgroup of patients taking ASA, and a subgroup of patients without ASA, is accompanied by a lower risk of strokes and systemic embolism and a lower incidence of major bleeding. The risk of stroke or systemic embolism was similar in patients with AF and PAD randomized to the apixaban group or to the warfarin group, as well as in patients with AF without PAD. Patients with AF and PAD who received apixaban or warfarin had a similar incidence of major bleeding or clinically significant minor bleeding.
451-457 175
The present review is focuses on new onset atrial fibrillation (AF) in conditions of acute coronary syndrome (ACS). Literature sources from PubMed and Scopus was used. AF is common in the general population and in the ACS population, at that new onset AF, and AF, which was by the time of ACS development are determined. Appearance of AF is more likely amongst the elderly patients with congestive heart failure, with signs of the hemodynamic instability and with the left atrium dilatation. It is well-known about the predictors of adverse outcome in ACS. According to some literature data new onset AF leads to worsening of prognosis, and in line with other sources a reason of its association with high level of mortality is due to the severity of ACS and appearance of AF is not independent predictor of death. The absence of subjective symptoms at the time of paroxysm of new onset AF does not allow estimating its duration and distinguishing between the new onset AF, persistent and constant AF. It is possible to trace the relationship between the myocardial ischemia and AF appearance. Inefficient reperfusion during percutaneous coronary intervention or thrombolytic therapy is accompanied by the onset of AF, on the contrary, when effective patency of coronary artery is achieved, AF appears significantly less often. New onset AF in ACS, in particular, accompanied by cardiogenic shock, requires emergency pharmacological or electrical cardioversion. In some cases, active cardioversion is not necessary, because of spontaneous cardiac rhythm conversion. In conclusions, it is necessary to point out, that ambiguity and multifactority of this problem demands investigation of arrhythmogenesis mechanisms and development of special risk stratification instruments for the new onset AF in ACS.


458-468 188
In the article, with regard to current clinical recommendations, the place of combined antihypertensive therapy, especially triple drugs regimens, is considered in the treatment of patients with arterial hypertension. Special focus is given to the body of evidence for the efficacy of valsartan and amlodipine, as the reference drug of angiotensin II receptor blockers and calcium channel blockers, respectively. Not only their high antihypertensive properties are demonstrated, but also a favorable effect on target-organ protection and prognosis is described. In particular, the possibilities of valsartan in reducing the severity of left ventricular hypertrophy and microalbuminuria are described, and its unique properties in the class of sartans that allow the use of this drug in patients with ischemic heart disease and chronic heart failure are emphasized. Data on the antiatherosclerotic effects of amlodipine and its proven ability to reduce cardiovascular risk are presented. Current data are presented about their use in a fixed-dose combination with hydrochlorothiazide, including real clinical practice settings. The evidence base of high clinical efficacy, safety and metabolic neutrality of the triple combination of antihypertensive drugs valsartan, amlodipine and hydrochorothiazide is presented. The issues of increasing adherence of patients to treatment when prescribing fixed-dose combinations are considered. An algorithm for the selection of antihypertensive drugs in the form of monotherapy and combination therapy of two or three drugs depending on the clinical situation (the presence of certain target-organs damages and associated clinical conditions, primarily ischemic heart disease, atherosclerosis of carotid arteries and chronic heart failure) and the severity of the additional risk of cardiovascular complications.

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)