Rational Pharmacotherapy in Cardiology

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Vol 13, No 2 (2017)
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146-154 2159

Aim. To estimate the rate of oral anticoagulants (OAC) prescription, continuity of anticoagulant therapy in hospital and ambulatory stages along with treatment adherence in patients with atrial fibrillation (AF) associated with hypertension (HT), ischemic heart disease (IHD) and chronic heart failure (CHF) within the registry of cardiovascular diseases. Material and methods. The study included 285 patients with AF combined with HT, IHD and CHF from the hospital registry RECVASA-CLINIC (n=3696). The rate of OAC prescription was evaluated in ambulatory and in-hospital stages according to medical records. Out-patient treatment was estimated via phone contact in 250 participants that represented 96.2% of all survived patients during follow-up of 24.1Ѓ}5.9 months after discharge from hospital. Medical adherence was evaluated using Morisky-Green questionnaire. Results. Mean age of patients was 73.9Ѓ}10.0 years (male – 52.6), CHA2DS2-VASc and HAS-BLED score were estimated as 5.14Ѓ}1.50 и 1.59Ѓ}0.79, respectively. Contraindications to OAC treatment were registered in 34 (11.9%) patients. In pre-hospital stage patients with paroxysmal AF received OAK more rarely comparing to those with permanent and persistent AF (31.8%, 51.7 and 55%, respectively; р<0.05). The rate of OAC administration in pre-hospital stage, on discharge and after 24.1Ѓ}5.9 months follow-up period was 40.4%, 88.1% and 82%, respectively, whereas patients with previous stroke were prescribed OACs more frequently (in 49%, 92.5% and 83.7% of cases, respectively). Only 43% of study participants had good compliance to medical treatment (score of 4) according to Morisky-Green questionnaire. Conclusion. OACs were under prescribed in pre-hospital stage and after 2 years of follow-up in patients with AF combined with HT, IHD and CHF comparing with in-hospital period (40.4% and 82% vs 88.1%). Medical compliance according to Morisky-Green questionnaire was not enough (43%) in high-risk patients after discharge from hospital.

155-163 1229

Aim. To study the efficacy and safety of the use of combined antihypertensive therapy with perindopril (as monotherapy or as a fixed combination with amlodipine or indapamide) together with lipid-lowering therapy with rosuvastatin, and to assess the level of satisfaction of doctors with the efficacy and safety of these combinations. Material and methods. 24 008 patients with arterial hypertension (HT) and dyslipidemia were included into the multicentre observational study. Researchers were free to choose a group of drugs and a prescription schedule. Inclusion criteria: age ≥18 years; the confirmed HT; combined therapy, including perindopril (monotherapy or fixed combination with indapamide or amlodipine) and rosuvastatin. The total duration of the study was 8 months (2 visits). At each visit, all patients underwent an office blood pressure (BP) and heart rate (HR) measurement, electrocardiogram registration, and assessment of lipids, electrolytes, creatinine, uric acid blood concentrations, and hepatic transaminase activity. Results. 10 330 men (43%) and 13 678 women (57%) were included into the study. The mean age of the patients was 61.83Ѓ}11.20 years. Ischemic heart disease was found in 9 792 (41%) patients, the history of myocardial infarction – in 12%, the history of stroke – in 6%, atrial fibrillation – in 2 428 (10%), chronic heart failure – in 15 449 (64%), diabetes mellitus – in 6 037 (25%) patients. Previous antihypertensive therapy was not available in 2 504 patients. A significant decrease in systolic and diastolic BP, HR was detected at visit 2 in patients using perindopril containing drugs (monodrug, fixed combinations with indapamide or amlodipine). Target systolic BP levels were achieved in 95% of patients with perindopril monotherapy, in 91% – with a fixed combination of perindjpril/indapamide, and in 88.6% – with perindopril/amlodipine. Doctors noted high satisfaction with the therapy. According to safety assessment the average score for perindopril monotherapy was 9.64, for a fixed combination of perindopril/indapamide – 9.61, for a fixed combination of perindopril/amlodipine – 9.64. Conclusion. Some aspects of the efficacy and safety of antihypertensive therapy in the SYNERGY study are discussed in this article. The use of combination therapy is associated with high efficacy, greater patient adherence to treatment and a lower incidence of discontinuation. All these provisions were confirmed in the SYNERGY study.

164-170 1592

Aim. Assessment of compliance the management of elderly patients (≥75 years) with acute coronary syndrome (ACS) with existing guidelines and evaluation of ACS features during the last two years of working period of the Regional vascular center and compare the results with the data from Russian and foreign registries, randomized clinical studies (RCS) and recommendations. Material and methods. Analysis of diagnostic and treatment data of 999 patients, aged 75 years and over, who were taken by ambulance or made their own way to N. I. Pirogov City Clinical Hospital №1 (CCH №1) in Moscow and were hospitalized during the period between the 1st January 2014 and the 31st of December 2015 in the intensive care unit for patients with myocardial infarction with the initial diagnoses of ACS, myocardial infarction and unstable angina. Results. The elderly patients with ACS admitted to the CCH №1 in 2014 and 2015 were 41% and 54% of all patients with ACS, respectively; women prevailed in all age subgroups. There was no age difference between the subgroups of ACS in patients with elevation ST-segment and ACS in patients without ST-segment elevation. A high frequency of comorbidity in the elderly patients with ACS was observed; hypertension was the most common disease with an incidence rate of 95% without significant difference between the genders. The incidence of percutaneous coronary intervention (PCI) and coronary angiography (CAG) significantly increased in 2015 compared with 2014 (p<0.0001, risk ratio 0.56, 95% confidence interval 0.420.76). A reduction in hospital deaths was also found (p<0.0001, risk ratio 1.51, 95% confidence interval 0.94-2.43). Dual antiplatelet therapy (DAT) was prescribed to elderly patients in clinical practice approximately in 70% of cases; DAT was performed significantly more often in 2015 than in 2014. Conclusion. There are a high percentage of the elderly patients with ACS admitted to the CCH №1. This proportion is dramatically higher than this in the Russian and foreign registries and RCS, that could influence on the outcome of patient care. The widespread use of interventional diagnostic and treatment methods (CAG and PCI) allows to improve substantially the clinical outcomes of ACS. A possibility of unconditional following the guidelines regarding the prescription of DAT to the elderly patients with ACS in real clinical practice may be limited by the high incidence of concomitant pathology.

171-177 934

Aim. To assess 5 years trend in level of doctor’s adherence to actual guidelines on secondary prevention of cardiovascular diseases in patients with a history of myocardial infarction in ambulatory specialized healthcare institution in Moscow. Material and methods. There were 752 patients firstly visited healthcare institution in 2006 and 825 patients – in 2011. Their data was included in two-stage retrospective pharmacoepidemiology study. Results. Prescription rate significantly increased for three of four prophylactic groups recommended for patients with a history of myocardial infarction (antiplatelets – 91.76%, beta-blockers – 83.39%, statins – 69.45%). When assessing prescribed doses of drugs, an increase in a number of their higher doses prescriptions was revealed (at the second stage of the study acetylsalicylic acid 100 mg/day received 75.32% of patients, enalapril 20 mg/day – 30.45%, simvastatin and atorvastatin 20 mg/day – 64.52% and 47.89% of patients, respectively). Conclusion. Results showed growing level of doctor’s adherence to actual recommendations on therapy and secondary prevention of cardiovascular diseases. Nevertheless, the level of adherence remains unsatisfactory and requires additional work with doctors.

178-183 1615

Ultrasound non-invasive coronary artery imaging contributes to the diagnosis of ischemic heart disease (IHD) in clinical practice. However, data of the prognostic value obtained from a complex analysis of contractility disorders and coronary blood flow parameters during exercise tests in the world literature are still not available. Aim. To develop risk models for adverse outcomes in patients with probable or definite IHD based on the results of a stress test with a noninvasive coronary blood flow study. Material and methods. Medical data of 689 patients with probable or definite IHD who underwent stress echocardiography with satisfactory visualization of the anterior interventricular artery (AIVA) were included in the analysis. All patients had stress echocardiography on a horizontal bicycle ergometer. Registration of coronary blood flow in the middle third of the AIVA was performed at rest and at the peak of the load with calculation of the coronary reserve value. Further patient follow-up lasted 3 years. Models of further negative outcomes were developed on the basis of the stress echocardiography results and of coronary blood flow parameters. Results. Three models that take into account the factors associated with further mortality, mortality/myocardial infarction and sum of negative outcomes were developed in the study. These models divide a cohort of patients with probable or definite IHD into groups of low, medium and very high risks. Factors associated with the risk of death include: age >56 years, load power <100 W, breach of contractility in the blood supply zone of the circumflex artery initially and during exercise, the difference in blood flow velocities in the AIVA<10 cm/s, coronary reserve of AIVA<2. The risk model of death, taking into account these factors, suggests dividing patients into low-risk group if there are ≤2 factors (mortality 0.6% for 3 years), medium risk – from 2 to 4 factors (mortality 1.8%), high risk – ≥5 factors (mortality 10.3% for 3 years). Conclusion. The study of coronary blood flow during stress echocardiography in addition to the analysis of left ventricular contractility in patients with probable or definite IHD contributes to determine the prognosis of further negative outcomes.

184-190 795

Aim. To study the efficacy of ivabradine in the prevention of cardiotoxic effects due to chemotherapeutic drugs in patients with breast cancer. Material and methods. The open randomized uncontrolled study included 55 patients with breast cancer who had to undergo chemotherapy by anthracyclines. The inclusion criterion was a heart rate >70 beats/min. Collection of complaints and anamnesis, ECG, echocardiography, routine laboratory tests were performed in all patients initially and after 1, 3, 6 and 12 months. All patients were treated with polychemotherapy with anthracyclines in combination with cyclophosphamide and fluorouracil. The patients included into the study were randomized into two groups. Patients of the main group (n=23) were additionally prescribed ivabradine in a daily dose of 10 mg followed by a dose titration. Patients of the control group (n=32) received only polychemotherapy. Results. In the main group a decrease in heart rate was observed already by the first month (from 83.6±9.5 to 67.1±7.5 beats/min, p<0.001) and persisted until the 6th month (74.2±14.9 beats/min, p<0.001). In the main group, the frequency of complaints of palpitation significantly decreased by the 1st month of treatment (from 60.9% to 30%, p=0.05) with a slight increase in further observation. A significant increase in the left atrium diameter (from 35.0±4.0 to 35.9±3.9 cm; p=0.009), the left atrium volume (from 42.0±12.8 to 43.7±11.6 ml; p=0.02), the end diastolic left ventricle (LV) volume (from 81.5±16.5 to 88.8±16.5 ml, p=0.007) and the end systolic LV volume (from 30.7±8.1 to 32.3±6.2 ml; p=0.01) were found in the main group in a month after polychemotherapy. Dynamics of the main echocardiographic indices was similar in the control group. By 6 months of observation the indexed mass of LV myocardium significantly increased in the control group (from 66.9±14.6 to 74.3±19.0 g/m2; p=0.024) in the absence of that in the main group (from 65.4±15.2 to 70.7±11.3 g/m2; p>0.05). A significant change in the LV ejection fraction was not found in both groups. Significant differences in LV global longitudinal strain were found between groups in 1, 3 and 6 months of observation (p<0.05), but after 12 months the groups were comparable in longitudinal strain values. Conclusion. Ivabradine therapy in patients with breast cancer and heart rate >70 beats/min was safe and did not cause bradycardia. Ivabradine use was accompanied by a significant reduction in a number of patients with complaints of palpitation, contributed to the preservation of normalLV global longitudinal deformation in chemotherapy, while the control group had negative changes with a maximum by the 6th month of follow-up.

191-196 582

Aim. To evaluate the nature of the dysfunction of the endothelium in postmenopausal women with climacteric syndrome, peculiarities of its changes during long-term use of a fixed low-dose combination of 17β-estradiol 1 mg/drosperidone 2 mg daily (Е2 1 mg/DRSP 2 mg). Material and methods. A non-randomized, uncontrolled study included 162 women in early postmenopausal period with climacteric syndrome. Patients were divided into 2 groups. Patients of the main group (n=84) received menopausal hormone therapy (MHT) with the fixed combination of Е2 1 mg/DRSP 2 mg. Patients of the control group (n=78) did not receive MHT. The duration of the follow-up was 5.2 years. The endothelium dependent vasodilation (EDVD) of brachial artery was assessed by reactive hyperemia. Endothelial dysfunction (ED) markers - plasma levels of endothelin-1 (ET-1), NO metabolites, asymmetric dimethylarginine (ADMA) and von Willebrand factor antigen (vWF:Ag) - were studied by a highly sensitive quantitative enzyme-linked immunosorbent assay. Results. The examined postmenopausal women with climacteric syndrome had significant increase in the concentration of ET-1 up to 1.0 (0.7-1.3) fmol/ml, increased levels of vWF:Ag up to 0.835 (0.760-0.990) U/ml and reduction in the level of the total content of stable metabolites of nitric oxide (NOx) to 39.2 (35.4-43.7) μmol/l. Disorders of EDVD of the brachial artery were observed in 50 (59.5%) women of the main group and in 45 (57.6%) women of the control group (p=0.7). The relationships between EDVD parameters and levels of ADMA (r=-0.31, p=0.029) and NOx (r=0.31, p=0.002) were revealed. In patients with impaired EDVD, a significant decrease in the level of stable NO metabolites and an increase in ADMA and ET-1 levels were detected. A significant increase in the EDVD of the brachial artery was observed throughout the follow-up period. Besides an increase in NO metabolites level, and decrease in the ET-1 and ADMA levels were found by the 12th month of MHT. Conclusions. Disorders of endothelial function were found in the majority of women in early postmenopausal period, the most marked changes were in patients with impaired vasoreactivity of brachial artery. Favorable changes in vascular endothelium function were observed during long-term MHT with the fixed combination of Е2 1 mg/DRSP 2 mg.

197-202 2898

Aim. To analyze the factors of medical choice in the prescription of medicinal drug (MD) for the treatment of cardiovascular diseases. Material and methods. A questionnaire survey of 212 doctors (138 physicians and 42 general practitioners) was performed in Irkutsk region and Republic of Buryatia. Questions were related to the physicians’ choice of the original or generic MD and the factors that influence this choice. Results. The majority of respondents prefer the foreign MD, while they prescribed both original and generic drugs (60.4%). The determining factor in the prescription of MD is its efficacy (91.5-95.3%). The main source of information of MD for physicians is the medical literature (78.3%). Only 23.6% of doctors choose the MD based on the results of clinical trials and information about it in specialized medical literature. A half of the respondents believe that their knowledge of cardiovascular MD is insufficient. Doctors need and are interested in information on the pharmacokinetics and pharmacodynamics of MD, side effects, drug interactions and results of clinical studies. Conclusion. It is necessary to focus on the clinical pharmacology of cardiovascular MD during the training of doctors in specialized courses of continuous medical education.


203-206 871

The article presents a case report of 86 years old patient S. (woman), hospitalized in the ophthalmology department of the hospital with a diagnosis of “complicated immature cataract of the left eye, open-angle glaucoma, age-related macular degeneration”. The patient experienced an episode of a fall with a short-term loss of consciousness, severe hypotension (blood pressure – 40/10 mmHg), and bradycardia (heart rate – 32 beats/min) while receiving a local form of beta-blocker in combination with diuretics. In this clinical case, the development of serious adverse reaction is significantly associated with adverse drug interaction (according to Horn-Hansten scale).


207-212 920

Aim. To assess the clinical and anamnestic characteristics, the prescription rate of angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) and β-blockers in the outpatient practice, adherence to drug therapy in patients with a combination of chronic heart failure (CHF), hypertension (HT) and history of myocardial infarction (MI) in the frame of Cardiovascular Disease Registry (RECVASA). Material and methods. Data analysis in groups of patients with a combination of CHF, HT and the history of MI (n=406) and patients with a combination of CHF, HT and ischemic heart disease (IHD) without history of MI (n=1897) was performed in the frame of RECVASA registry. The structure of the associated cardiovascular and concomitant non-cardiac diseases, the severity of the clinical manifestations of CHF, IHD and HT, the prescription rate of the ACEI/ARB and β-blockers, the adherence to drug therapy (according to the Morisky-Green test) were studied in groups. Results. Patients with a combination of CHF, HT and IHD with or without MI history significantly differed in the proportion of men (47.8% vs 24.9%, respectively), prevalence of atrial fibrillation (25.9% vs 20.5%, respectively), diabetes mellitus (27.3% vs 15.7%, respectively) and the stroke history (17.2% vs 10.7%, respectively). The mean age (69.9±11.0 vs 70.3±11.0 years, respectively), as well as the prevalence of the history of respiratory diseases, chronic kidney disease, digestive diseases, obesity and anemia, did not differ significantly. Patients with a combination of CHF, HT and post-infarction cardiosclerosis (PICS) compared with patients without PICS significantly more often had CHF class 3-4 NYHA (62% vs 47.9%, respectively), HT of degree 3 (92.5% vs 84.2%, respectively), stable angina class 3-4 (84.4% vs 66.4%, respectively). Patients with PICS significantly (p<0.05) more often received β-blockers (56.7% vs 42.2%, respectively), a combination of ACEI/ARB plus β-blockers (44.6% vs 35.1%, respectively), but less often – monotherapy with ACEI/ARB (73.7% vs 77.6%, respectively). The proportion of patients with adherence to treatment (4 points on the Morisky-Green scale) was greater in patients with PICS (37.2% vs 30.6%, respectively; p<0.05). Conclusion. Patients with CHF in combination with HT and PICS compared with patients without PICS had more prevalence of atrial fibrillation, diabetes mellitus and stroke history, more severe course of CHF, HT and IHD, greater prescription rate of β-blockers, combinations of ACEI/ARB plus β-blockers, but less prescription rate only ACEI/ARB, higher adherence to treatment. The prescription rate of prognostically significant ACEI/ARB and β-blockers in these patients is inadequate, and only one third of patients are adherent to treatment.


213-220 2040

Aim. To study the relationship of psychological factors (perfectionism and mechanisms of psychological defense), with the presence and qualitative characteristics of the "burnout syndrome" in patients with "workplace hypertension" (WPH), in comparison with other patients with essential hypertension (HT) and healthy individuals. Material and methods. 170 untreated patients with stage II HT (mean age 46.7±4.1 years) were examined. 85 patients with WPH were included into group 1 (46 men; mean age 44.7±4.3 years) and 85 patients without WPH – into group 2 (42 men; mean age 47.4±4.5 years). The control group consisted of 82 healthy individuals (45 men; mean age 44.9±3.1 years). The Russian version of Maslach Burnout Inventory (MBI), the Multidimensional scale of perfectionism by Hewitt and Flett (MPS), The Life Style Index (LSI) were used for “burnout syndrome” diagnose. Results. The relationship between perfectionism and "burnout" was found in all studied groups. The factor "socially prescribed perfectionism" was most associated with the "burnout" parameters in both groups of HT patients. In the WPH-group this relationship was more pronounced. The structure of perfectionism in WPH-patients is the most disharmonious in comparison with patients of the group 2 and healthy persons. The "socially prescribed perfectionism" was significantly more prevalent (76.6±3.9) compared with other indicators (62.1±4.3 and 61.5±3.6 for perfectionism oriented to others and to themselves, respectively). In the structure of the protective processes in HT patients of both groups with the maximal degree of excess of the values of healthy individuals two most archaic mechanisms [projection (69.1% and 40.8%) and negation (51.8% and 40.9%) in groups I and II, respectively] as well as one of the most mature protective processes (intellectualization - 53% and 47.9%, respectively) were revealed. Taken together, this shows a general "tension" of the system of protective processes. Statistically significant correlations between the high representation of the protective processes "negation" and "projection" with high values of the score according to MBI scales were found. Conclusion. Perfectionism and the "tension" of the mechanisms of psychological defense can be considered as the most important personal characteristics predisposing to the development of "burnout syndrome" in WPH-patients.

221-228 929

The main results of psychosomatic studies are summarized. A high incidence of mental health disorders is shown in patients with somatic diseases. They worsen the prognosis, increase the severity of the condition, make diagnosis and treatment more difficult, reduce the quality of life and work capacity, increase healthcare costs. Antidepressants decrease severity of anxiety and depression, as well as diminish frequency of somatic events and hospitalizations in patients with depression. It is important to take into account the influence of psychotropic drugs on somatic diseases and their treatment. It is important to improve the training of doctors and develop national guidelines for improving the diagnosis and treatment of patients with comorbid somatic and mental diseases.


229-237 891

Working group of the “GRANAT-2” study: Tula - Trubitsyn G.I., Ivanov Yu.V., Mirenkova O.K., Eskova R.A., Simonova R.P., Milon M.E., Telegina E.V., Kuznetsov A.M., Zhukova N.A., Zainullina I.K.; Rostov-on-Don - Budanov O.V., London E.M., Minosyan L.V., Nedashkovskaya N.G., Ter-Ananyants Ye.A.; Tomsk - Proskokova I.Yu., Permyakova O.V., Politova L.V., Maneeva I.D., Ivanova S.Yu.; Nizhny Novgorod - Larina O.V., Pokrovskaya I.N., Patselt E.A.; Moscow - Sladkova T.A., Zelenova Т.V. 

Aim. To study the tolerability and adherence to antihypertensive therapy in patients with hypertension and chronic obstructive pulmonary disease (COPD) using the fixed combination of ramipril and amlodipine in the observational program for patients with arterial hypertension and COPD (GRANAT-2). Material and methods. Patients with hypertension and COPD (n=52) with all inclusion criteria and without exclusion criteria who signed informed consent to participate in the GRANAT-2 program were included into the study. The use of a fixed combination of ramipril and amlodipine was recommended in all patients. The doses were determined by the treating physicians in accordance with the official drug instruction. The patients had 4 visits, and the duration of the study was 5 months. The Morisky-Green test was used to assess an adherence of patients to treatment. Assessments of blood pressure, adverse events were performed at all visits. Results. 50 of 52 patients completed the study: 45 patients used the studied fixed combination in the recommended doses, and 5 patients used other antihypertensive drugs, 2 patients withdrew from the study. Systolic blood pressure after 1 month of treatment decreased by an average of 20 mm Hg from the baseline, and diastolic blood pressure – by 10 mmHg. These rates after 5 months of therapy were 29 mm Hg and 15 mm Hg, respectively. Target blood pressure level was achieved in all patients. Increase in adherence of patients to treatment (according to the Morisky-Green test from 21.1% to 65.1%) was found. 2 cases of adverse events (dry cough) were registered. The discrepancy in adherence assessment was revealed between the results from the Morisky-Green test and the data from program case report forms. Conclusion. Regular patient visits to the doctor and the rapid achievement of an antihypertensive effect with good tolerability of a fixed combination of ramipril and amlodipine contributed to the increase in adherence of patients to treatment. Undesirable effects of the drug therapy are significant, but not leading factors that have a negative impact on the patient adherence to treatment.


238-247 1806

Possibilities and prospects for the clinical use of enhanced external counterpulsation (EECP), which has long established itself throughout the world, are discussed in the article. Historical background, as well as the development stages of EECP for the treatment of patients with coronary heart disease (CHD) and chronic heart failure (CHF) are considered. The mechanism of action of the EECP and the main hemodynamic, neurohumoral and tissue effects that justify its use are presented. The effect of EECP on endothelial function and coronary reserve, disorders of which occurs in the majority of cardiovascular diseases, is considered separately. Treatment of patients with CHD, including complicated by CHF, are the most studied indications for EECP using in medical practice. The evidence base for treatment of patients with these disorders by EECP is presented in the article. Prospects for the EECP application in other areas of medicine are also presented.

248-255 3915

Speckle-tracking echocardiography is promising modern technique for evaluation of structural and functional changes in the myocardium. It evaluates the indicator of global longitudinal myocardial deformation, which is more sensitive than ejection fraction to early changes of left ventricular contractility. The diagnostic capabilities of speckle tracking echocardiography are reflected in clinical recommendations and consensus statements of European Society of Cardiology (ESC), European Association of Cardiovascular Imaging (EACVI) and American Society of Echocardiography (ASE). The aim of this paper is describe basic principles of speckle tracking echocardiography and clinical applications of this new technology. Attention is paid to the use of speckle tracking echocardiography in such heart pathologies as heart failure, coronary heart disease and myocardial infarction, left ventricular hypertrophy in arterial hypertension, hypertrophic cardiomyopathy and amyloidosis of the heart, valvular heart disease, constrictive pericarditis and cancer therapy-induced cardiotoxicity.


256-262 1638

Aim. To study the location of pravastatin, simvastatin, fluvastatin and cerivastatin in molecular complexes with model cell membranes based on dodecylphosphocholine, and also to calculate the average interatomic distances between the atoms of statins and micelles. Material and methods. Nuclear magnetic resonance (NMR) spectroscopy was chosen as a method of study. NMR spectroscopy of the Overhauser nuclear effect (NOESY) is one of the most effective methods in the study of intermolecular interactions, in particular, in studies of drugs. Information on the spatial structure of the molecular complex, as well as on the fragments of molecules responsible for the effective interaction leading to complex formation, was obtained by NOESY spectroscopy. All NMR experiments were performed on a Bruker Avance II 500 spectrometer with a 5 mm zgradient inverse sensor with the TOPSPIN software. The calculation of the interatomic distances was made with an accuracy of 0.1 A. Results. The location of pravastatin, simvastatin, fluvastatin and cerivastatin in molecular complexes with model cell membranes based on dodecylphosphocholine was determined based on NMR NOESY experiments. The average interatomic distances between the atoms of statins and micelles were also calculated. Pravastatin weakly binds to the polar surface of the model membrane, while simvastatin penetrates into the space between the hydrocarbon chains of the micelle. Fluvastatin interacts mainly with model membranes by penetration of its aromatic fragments into the surface of the micelle. Cerivastatin has a unique arrangement in the model membrane. It is located deep in the hydrophobic nucleus of the micelle close to the terminal methylene group. Conclusion: Even minor differences in the chemical structure of statins lead to different patterns of interaction with model membranes. These differences can explain the characteristics of the pharmacological properties of these substances.


263-269 5806

The importance of renin-angiotensin-aldosterone system in pathogenesis of different clinical conditions is studied well. The key role of aldosterone receptor blockers, particularly spironolactone, in treatment of such conditions as primary hyperaldosteronism, resistant hypertension, edematous syndrome in congestive heart failure, nephrotic syndrome, and portal cirrhosis is considered in the article. Development of ideas about cardio-, vaso- and nephroprotective effects of these drugs is highlighted as well as their influence on patient prognosis.

270-274 599

The role of randomized controlled trials (RCTs) and observational studies in evaluation of the efficacy and safety of drugs in cardiology is discussed. The possibility of using the results of non-interventional studies in accepting the decision to choose the most effective and safe drug is presented in more detail.


275-283 702

Advanced age is the most important and independent risk factor for the development of atrial fibrillation (AF). The proportion of patients with AF at the age of 65-85 years reaches 70%, and average age of patients with AF is 75 years. Antithrombotic therapy of AF in the elderly is challenging for several reasons. On the one hand, elderly patients are at an increased risk of systemic embolism and stroke and fatal outcomes of stroke are higher in the elderly compared with these in the younger patients. On the other hand, elderlies are at an increased risk of bleeding. In addition, they have important comorbidities and are treated with drugs that can interact with antithrombotic agents. The article discusses tools used to assess risks of thromboembolic and hemorrhagic complications and general approaches to antithrombotic treatment of elderly patients.


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