Rational Pharmacotherapy in Cardiology

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Vol 14, No 6 (2018)
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804-815 151
Aim. To evaluate the availability and affordability of medicines used to treat of cardiovascular diseases (CVD) in several regions of the Russian Federation with different climatic, geographic, economic and demographic characteristics. Material and methods. The study was conducted in 6 regional capitals, chosen to differ in geographically, economically, and demographically. In each city, 5 pharmacies providing free medicines to certain categories of citizens (beneficiaries) and 5 private pharmacies serving anyone were selected at random. Medicine availability was assessed in all pharmacies, along with price only in the private pharmacies. Data were obtained for both original drug and appropriate generics. A list of 25 of the most frequently prescribed medicines for cardiovascular diseases was compiled. Results. Some general findings emerged. With the existence of a generic drug, the original drug was not available in the pharmacy supplying beneficiaries. Diuretics, as well as some ACE inhibitors, are not available in a number of pharmacies for beneficiaries. Enalapril in most licensed pharmacies is represented by generics, lisinopril in a number of cities is represented by both the original drug and generics. The presence of sartans was much lower than ACE inhibitors. Bisoprolol was most common beta-blocker. Calcium antagonists: if amlodipine was present in all licensed pharmacies, at list as generic, then nifedipine was not available in many licensed pharmacies. Among antiplatelet agents, aspirin was available in most pharmacies, and clopidogrel was mostly represented by generics. As for statins, only simvastatin could be found in almost all pharmacies. When analyzing the cost of drugs in licensed pharmacies, it was found that drugs containing furosemide are the cheapest among generics – about 17 rubles. The most expensive treatment with generics of rosuvastatin – about 4,374 rubles a month. The most expensive original medicine was also rosuvastatin – about 4,500 rubles for 30 tablets, the cheapest – the original drug of furosemide – about 35 rubles. On average, the cost of CVD treatment with major classes of drugs, including ACE inhibitor, beta-blocker, antiplatelet drug and statin, is 1,921.9 rubles per month. Conclusion. The basic cardiovascular medicines were characterized by a relatively high availability in 6 regions of the Russian Federation included in the analysis both by the criterion of the availability of drugs and by the criterion of the minimum price.
816-825 101
In hypertensive patients, blood pressure variability (BPV) and comorbidity are associated with prognosis. However, there have been no complex prospective studies of BPV in patients with hypertension and chronic lower airway diseases (CLAD). Aim. To investigate specific features of different BPV types and their prognostic value in hypertensive patients with and without CLAD in a prospective study. Material and methods. This prospective cohort study included hypertensive patients, approximately half of whom had asthma or chronic obstructive pulmonary disease (COPD). Clinic blood pressure (BP) measurements, ambulatory and home BP monitoring (ABPM, HBPM), spirometry, clinical blood analysis and blood chemistry, and a standard questionnaire and physical examination were performed at baseline and 12 months later. Clinical BP measurements and HBPM were also repeated 6 months after the baseline visit. At 12 months from the last study visit, we collected the information about cardiovascular complications and deaths. Statistical methods included ANOVA and survival analysis. The BPV indices were calculated as SD for different time periods, ARV (average real variability), and VIM (variation independent of mean). The inter-group comparisons were adjusted for age and sex. The assessment of intra-visit and long-term BPV was based on clinical BP measurement. The assessment of 24-hour BPV and mid-term BPV was based on ABPM and HBPM, respectively. Results. The BPV levels, assessed by ABPM and HBPM, were higher in patients with CLAD. There were no long-term BPV differences between two groups, in according to clinical BP data. Higher levels of daytime BPV were associated with orthostatic systolic BP, baseline forced expiratory volume in 1 second (FEV1), and glomerular filtration rate (GFR). An increase in nighttime BPV was associated with COPD, serum creatinine, FEV1 after β2-agonist inhalation, and GFR. In the CLAD group, the cumulative survival was lower, while the total risk was higher. The following endpoint predictors were identified: supraventricular arrhythmias, SD of nighttime diastolic BP, blood leukocyte count and nocturnal BP fall (Wald Chi-Square 14.780- 4.257; p<0.0001-0.026). Conclusion. The main BPV indices are higher in patients with asthma and COPD, in comparison with CLAD-free hypertensive patients. ABPM is the most reliable method of BPV assessment in hypertensive patients with CLAD, according to our data. The increase in BPV is associated with irreversible airway obstruction and renal function. Adverse outcomes were associated with both nighttime BPV and nocturnal BP fall, as well as with rhythm disorders and leukocyte count as a marker of systemic inflammation. BPV in patients with CLAD warrants further investigation.
826-830 103

Aim. To compare safety of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF). Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no significant differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg). Results. There were no mortality, stroke, transient ischemic attack, ventricular arrhythmia, asystole longer than 3,0 sec (primary safety criteria) in both groups. Prolongation of QT interval longer than 500 ms observed in 1 of 30 patients (3,3%) in DCC group and in 7 of 30 patients (23,3%) in PCV group. 2 patients (one patient in each group; 3,3%) developed asymptomatic bradycardia after conversion to SR that resolved spontaneously within 30 minutes. 95% confidence interval (95%CI) for secondary safety criteria is [0,02-0,38] for QT prolongation and [-0,04-0,04] for bradycardia. Conclusion. Safety of PCV is noninferior to DCC in patients with persistent AF in terms of primary safety criteria and bradyarrhythmias. More frequent QT interval prolongation to values >500 ms observed in PCV group points to necessity of precautions with use of the drug.

831-839 149
Aim. To investigate the impact of valsartan/amlodipine single-pill combination (V/A SPC) on arterial stiffness parameters and 24-hours blood pressure (BP) level in the middle-aged patients with stage II grade 1-2 essential arterial hypertension (HT). Material and methods. A group of patients with stage II grade 1-2 HT who had not previously received regular antihypertensive therapy (n=38, age 49.7±7.0 years) was retrospectively formed. All the patients were treated with V/A SPC and all of them achieved target office BP (<140/90 mm Hg). 12 weeks after reaching the target BP the assessment of V/A SPC therapy effectiveness and vascular stiffness (general clinical data, ambulatory BP monitoring, volume sphygmography, echocardiography) were performed in all included HT patients. Sex- and age-matched healthy people with normal BP (n=86, age 48.8±5.8years) and in whom similar clinical and vascular stiffness data were available represented a control group. Results. According to the ambulatory BP monitoring data systolic, diastolic and pulse BP significantly (p<0.001) decreased after the treatment with V/A SPC. Volume sphygmography has showed significant decrease in right-CAVI value from 8.9±1.3 to 7.3±1.4 (p=0.021) as well as a reduction the number of patients with a right- and/or left-CAVI>9.0 from 31.6 to 10.5% (p=0,049). According to an assessment of arterial stiffness the augmentation index decreased significantly by 23.6±8.6% from -23.0±17.1 to -28.9±18.7 (p=0.034. Transthoracic echocardiography data has demonstrated decrease in effective arterial elastance from 1.73±0.35 to 1.60±0.32 mm Hg (p=0.016) and increase in the arterial compliance – from 1.30±0.38 to 1.43±0.34 mm Hg/ml (p=0.049). Conclusions. In naive patients 40-65 years old with stage II grade 1-2 HT antihypertensive therapy with V/A SPC provides effective 24 hours BP control and improves arterial stiffness parameters.
840-845 106
Aim. To evaluate the antihypertensive efficacy and tolerability of a fixed combination of amlodipine and ramipril in hypertensive patients with very high cardiovascular risk. Material and methods. A retrospective cohort study of real clinical practice of prescribing antihypertensive drugs according to 255 medical records of outpatient hypertensive patients with a history of acute coronary syndrome (ACS) and coronary artery stenting was performed in the first part. An open observational study was performed in the second part. 69 people older than 18 years with a history of ACS and coronary artery stenting, without reaching the target blood pressure (BP) level while using free combinations of antihypertensive drugs and with indications for a fixed combination of ramipril and amlodipine were included into the study. Analysis of self-monitoring of BP, office BP, daily BP monitoring (ABPM) and patients’ adherence to treatment (Morisky-Green test) initially, after 4 and after 12 weeks of taking the fixed combination of ramipril and amlodipine was performed to assess the clinical efficacy of the studied drug. Results. It was found that 42.0% of patients did not follow the recommendations for regular intake of antihypertensive drugs. So, hypertension of all patients regarded as false-refractory, which was the basis for the prescription of the fixed combination of ramipril and amlodipine in accordance with clinical guidelines for the diagnosis and treatment of hypertension. After 4 weeks of therapy, there was significant decrease in office BP with the achievement and preservation of the target level by the 12th week, normalization to the 12th week of day and night BP variability in 54.9% of patients. 78.0% of patients followed medical recommendations for regular administration of antihypertensive drugs, none of the patients had adverse events. Conclusion. The use of fixed combinations of drugs, in particular, amlodipine and ramipril as a part of multicomponent therapy in hypertensive patients with very high cardiovascular risk, led to the achievement of target BP by the 4th week of therapy and stable preservation of antihypertensive effect in 12 weeks of treatment as well as gradual normalization of day and night BP variability in more than half of patients. Fixed combination of ramipril and amlodipine allowed to improve adherence of patients to cardiovascular diseases.
846-851 73
Aim. To study the effect of two regimens of combined antihypertensive therapy during the day on daily monitoring of arterial pressure, central aortic pressure, and arterial stiffness, depending on the salt sensitivity of hypertensive patients with diabetes mellitus type 2. Material and methods. 130 hypertensive patients with type 2 diabetes mellitus were included into the study. They were divided into 2 subgroups: salt-sensitive (group 1) and salt-resistant (group 2), and then randomized to subgroups A and B of ongoing therapy: in the morning ramipril and indapamide retard, bedtime – amlodipine (subgroup 1A and 2A); or in the morning amlodipine and indapamide retard, bedtime – ramipril (subgroup 1B and 2B). Initially and after 24 weeks of antihypertensive therapy, 24-hour blood pressure monitoring was performed, the indices of central aortic pressure and arterial stiffness were determined. Results. After 24 weeks, in all subgroups, there was a significant positive dynamics of the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices. In the subgroup 1В, it was registered a significant improvement in the majority of parameters of 24-hour blood pressure monitoring (decrease in 24-hours systolic BP by 24.4%, 24-hours diastolic BP by 22.1%; p<0.05), central aortic pressure (decrease in aortal systolic BP by 15.9%, aortal diastolic BP by 20.8%; p<0.05) and vascular wall stiffness parameters (decrease in pulse wave velocity by 13.8%; p<0.05) in comparison with group 1A (decrease in 24-hours systolic BP by 17.5%, 24-hours diastolic BP by 14.6%, aortal systolic BP by 12.7%, aortal diastolic BP by 9.7%, pulse wave velocity by 9.2%; p<0.05 in comparison with the group 1B). In the case of salt-resistant patients, there were comparable positive changes in the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices against the background of both dosing regimens during the day. Conclusion. In the study, it was demonstrated the more pronounced antihypertensive and vasoprotective efficacy of the combination of thiazide-like diuretic with calcium channel blocker in the morning and ACE inhibitor in bedtime compared to the alternative regimen of prescribed pharmacotherapy in salt-sensitive patients, and comparable efficacy of both regimens in salt-resistant hypertensive patients with diabetes mellitus type 2.
852-857 69

Aim. To study the prescribed drug therapy, as well as adherence to it in patients with acute coronary syndrome (ACS) in real clinical practice within a year after the index event. Material and methods. The study included 327 patients who were in hospital treatment with ACS: 199 patients (60.9%) with unstable angina (UA) and 128 (39.1%) – with acute myocardial infarction (AMI). The prescribed treatment and adherence to therapy were evaluated within 12 months after the coronary event. Therapy prescribed to patients was compared with current clinical guidelines for the treatment of patients with ACS. Results. 67% of patients completed the clinical study Adherence to prescribed medication within 12 months after ACS was maximal for ACE inhibitors/angiotensin receptor blockers (83.6%), dual antiplatelet therapy (79.9%) and β-blockers (78.1%), and minimal for lipid-lowering drugs (statins; 61.6%). A significant decrease in adherence was revealed in 6 and 12 months from the initiation of therapy. Significantly higher level of adherence to DAT was found in patients with AMI compared with patients with UA (p<0.05). When analyzing the frequency of occurrence of endpoints, it was found that patients who did not adhere to treatment significantly more often had hospitalizations due to UA (15.1% vs 7.4%; p<0.05), AMI (16.9% vs 8.1%; p<0.05), death from cardiovascular causes (13% vs 10.4%; p<0.05). Conclusion. Therapy prescribed at the outpatient stage in patients with ACS in the Rostov Region corresponds to the modern clinical recommendations. Six months after hospital discharge adherence to drug therapy in patients is reduced, which requires more careful outpatient monitoring during this period. In patients who are not adherent to treatment, cardiovascular complications are significantly more frequent.

858-863 146

Aim. To study the frequency of oral anticoagulants (ОАС) prescription for patients with atrial fibrillation (AF) after myocardial infarction (MI). Material and methods. The study includes 106 patients (60 men, 55.6%) with a previously established diagnosis of AF, who were on hospital treatment in the period 2016-2017 years in one of the university hospitals of the city and having at the time of discharge from the hospital the final diagnosis of МI. The median age was 70.0 (61.0;78.0) years. Patients with the first and only paroxysm of AF were excluded from the analysis and all further calculations were performed for 104 patients. In 64 (60.2%) of cases, AF was presented by paroxysmal form, while in 2 (1.9%) cases this paroxysm was the first and only, in 20 (18.9%) cases – persistent AF and in 20 (18.9%) – pernanent. Results. While assessing the risk of thromboembolic complications on the CHA2DS2-VASc scale, the median score for all patients was 5.0 (4.0;6.0) points. While assessing the risk of hemorrhagic complications on the HAS-BLED scale, the median score for all patients was 2.0 (2.0;3.0) points. HAS-BLED≤2 value had 71 (68.3%) patients, HAS-BLED≥3 – 33 (31.7%). Only one antiplatelet agent was prescribed to 4 (3.8%) patients. Aspirin was the only antiplatelet agent in 3 cases and clopidogrel – in one case. In 80 (76.9%) cases, patients were prescribed dual antiplatelet therapy, in 17 (16.3%) – ОАС therapy, among which 7 (6.7%) cases – a triple antithrombotic therapy (ATT), 9 (8.7%) cases – a double ATT (ОАС+ antiplatelet agent) and 1 (1.0%) case – a monotherapy. Among all cases of OAC prescription warfarin was prescribed in 11 (64.7%) cases and rivaroxaban – in 6 (35.3%). Conclusion. In real clinical practice, the prescription or refusal of ОАС occurs without taking into account the risk of thromboembolic and hemorrhagic complications according to appropriate scales.


864-869 142
A case of successful cardiopulmonary resuscitation lasting 120 min with a good neurological outcome in a patient with acute coronary syndrome is presented. The protocol of resuscitation with the use of thrombolysis (recombinant non-immunogenic staphylokinase) followed by stenting of the infarct-dependent artery in a patient with acute coronary syndrome is described on the example of this case.


870-878 94
Rheumatoid arthritis (RA) is characterized by a twofold increase in morbidity and mortality due to chronic heart failure (CHF). At the same time, the prevalence of CHF among RA patients is significantly underestimated. The aim of the review was to analyze the results of the main studies on the features of the clinical presentation of heart failure (HF) in RA patients, the role of visualization techniques and biomarkers in the diagnosis of HF and preclinical dysfunction of the myocardium. HF in patients with RA is characterized by a predominance of HF with a preserved left ventricular ejection fraction (LVEF). The use of clinical diagnostic criteria in RA patients can lead to both over- or underdiagnosis of CHF. Systolic dysfunction estimated by LVEF is rare in RA and does not reflect the real frequency of myocardial dysfunction. Echocardiography (ECHO-CG) with tissue Doppler echocardiography (TDE) and visualization of myocardial deformation, magnetic resonance imaging (MRI) of the heart in RA patients revealed a high frequency of HF with preserved ejection fraction, left ventricular remodeling and hypertrophy, pre-clinical systolic and diastolic dysfunction. Determination of natriuretic peptides is useful for verifying the diagnosis of HF and estimating the prognosis in this cohort, despite the possible decrease in the sensitivity and specificity of these indicators in RA patients. The review discusses the advantages of MRI of the heart, including quantitative T1 and T2 regimens, in the diagnosis of myocarditis, myocardial fibrosis, and myocardial perfusion disorders in RA patients. In order to verify the diagnosis of heart failure and detect pre-clinical myocardial dysfunction in RA patients, the determination of natriuretic peptides concentration should become part of the routine examination, beginning with the debut of the disease, along with the collection of a cardiological history, physical examination, ECHO-CT with TDE, and visualization of myocardial deformation. Evaluation of the quantitative characteristics of tissue according to MRI of the heart could improve the diagnosis of myocardial damage.


879-886 72

Aim. To evaluate the structure of combined cardiovascular diseases, drug treatment and observation of patients with a history of stroke in the framework of prospective outpatient registries. Material and methods. The study was conducted based on 3 outpatient clinics of Ryazan city. Patients with a history of acute cerebrovascular accident (ACVA) of any remoteness (AR) were included into ACVA-AR outpatient registry (n=511). Patients who had visited the outpatient clinics for the first time (FT) after cerebral stroke (n=475) were included into the ACVA-FT outpatient registry. The structure of the cardiovascular diseases (CVD), compliance with the clinical recommendations of the prescribed and received drug therapy were evaluated. The proportion of patients with dispensary observation for CVD, using preferential drug provision was determined. Results. A combination of 2 or more CVDs was found in 84.4% and 82.5% of cases, and severe cardiovascular multimorbidity (3-4 CVDs) – in 69% and 64% of cases, respectively, in ACVA-AR and ACVA-FT registers. Compliance with the clinical guidelines prescribed and received drug therapy was insufficient at the outpatient stage. Necessary prescription of drugs with a proven beneficial effect on the prognosis were observed significantly more frequent in the ACVA-FT registry, compared to the ACVA-AR registry at the enrolling stage of the study (p<0.05): statins for stroke – 50.1% vs 25.2%; statins for coronary heart disease (CHD) – 47.2% vs 27.9%; antiplatelet agents for CHD without atrial fibrillation – 65.6% vs 54.3%; anticoagulants for atrial fibrillation – 17.7% vs 9.3%; beta-blockers for heart failure 43.5% vs 33.1%, respectively. After 2-3 years of the follow-up frequency of prognostically significant prescriptions in patients of the compared registries were not significantly different, except prescriptions for statin therapy (47.6% vs 21.3%, respectively). The prognostically significant prescriptions during the enrolling stage in ACVA-AR and ACVA-FT registries occurred in 44.4% and 54% of the total number of proper prescriptions, and in the long-term follow-up period – in 55% and 57%, respectively; and the dispensary observation coverage was only 35.0% and 31.8%, respectively. According to patient contact only 21-24% of patients used the system of preferential drug provision at the stage of inclusion into the registers, and after 2-3 years of follow-up – 1.5-2 times less (12-14%). Conclusion The results of the study REGION found the presence of cardiovascular multimorbidity in 83% of patients with a history of stroke, insufficient quality of prescribed drug therapy in the out-patient clinic, especially in the ACVA-AR registry. The quality of medical treatment of patients improved within 2-3-year follow-up after the reference visit to out-patient clinic, but not sufficiently. Increase in dispensary observation coverage and optimization of the system of preferential drug provision are also important reserves for improving the quality of treatment of patients with a history of stroke, as well as prevention of cardiovascular complications.



887-890 86
The quality of the database analysis that led to the conclusion that angiotensin converting enzyme inhibitors contribute to the development of lung cancer is analyzed. The author notes that the analysis of the potential risk from taking these drugs is possible only if it is related to the proven positive effect of these drugs on the prognosis of life in certain categories of patients, primarily with chronic heart failure and a history of acute myocardial infarction. Attention is drawn to the methodological errors of the study, putting the main conclusion of the analysis into question.
891-900 77
Aim. To study adherence to treatment with generic statins prescribed to patients with high and very high cardiovascular risk in routine clinical practice, as well as the possible impact of educational training of doctors on compliance with clinical guidelines and changes in patient adherence to treatment. Material and methods. The study was prospective, with educational training for physicians on the main provisions of current clinical guidelines prior to the program. It included 3 visits over 12 weeks: inclusion visit (V0), and visits after 1 and 3 months of follow-up (V1 and V3). The use of generic atorvastatin or rosuvastatin was recommended for all patients. To assess adherence the following surveys were used: medical survey (all visits), the original questionnaire to assess the potential and the actual commitment to taking statins and the causes of non-adherence, and the Morisky-Green 8-question test (visits V0 and V3) to evaluate overall adherence to drug treatment. The patients who started the drug taking according to the medical recommendations and continued it during the study were considered as adherents. Patients who started but stopped taking the drug for 12 weeks were considered as partially non-adherent. Patients who refused to take the recommended statin were considered as non-adherents. The prescribed doses of statins and medical tactics in the titration of doses, as well as the achievement of the target level of low-density lipoprotein cholesterol (LDL cholesterol) were evaluated. Results. 112 (37.5%) of the 298 patients with baseline indications for taking statins did not take these drugs. According to the medical survey at V0 a total of 286 (96%) patients were potential adherents to medical recommendations; at V3 262 (88%) patients were adherent to statin treatment; 34 patients were partially non-adherent, 1 – was non-adherent, and 1 – dropped out of the study immediately after V0. According to the original questionnaire, potential adherence was assessed in 281 patients: 244 (86.8%) were potentially adherent, 37 (13.2%) – partially non-adherent. At V3, out of 294 patients who filled in the original questionnaire, 260 (88.5%) were adherent, 26 (8.8%) – partly non-adherent, 8 (2.7%) – nonadherent. The Morisky-Green questionnaire was filled in by 292 patients: at V0, 106 patients (36.3%) had treatment adherence, non-adherence – 186 patients (63.7%). By V3, an increase in total adherence was found: 159 patients (54.5%) were adherent, and 133 (45.5%) – non-adherent. The lipid profile was evaluated in 231 patients in V1 and in 285 ones – in V3. The target LDL cholesterol level was reached by V1 in 47 (20.3%) patients, and in 184 (79.7%) patients – was not. Dose titration occurred in 56 patients. By V3, 121 (42.4%) patients reached the target level of LDL cholesterol, and 164 – did not. The results of the lipid profile analysis were erroneously interpreted in 21 patients. Conclusion The results of the medical survey and the original questionnaire for assessing adherence predominantly coincided. The Morisky-Green test does not accurately reflect patients' commitment to taking a particular drug. Clinical inertness of doctors in the titration of statin doses and achievement of target LDL cholesterol levels were found as well as erroneous interpretation of the LDL cholesterol level. Educational trainings for doctors had a positive effect on the implementation of clinical guidelines, and also contributed to increasing patient adherence to medical recommendations.


901-907 51
The key to successful treatment in patients with acute coronary syndrome is maximally early revascularization of the coronary arteries. Treatment of multifocal atherosclerosis with lesions of the coronary and peripheral arteries requires coordinated work of the multidisciplinary team of doctors. Critical ischemia of the lower limbs requires urgent revascularization in order to prevent limb amputation. However, it is not always possible to perform revascularization using specialists of the same profile – endovascular or surgical. The use of hybrid methods of treatment (surgical and endovascular) allows to significantly improve the prognosis in saving the limb. The article presents a clinical observation of successful multistep treatment of a patient with acute coronary syndrome in combination with critical ischemia of the lower limb. The first stage was performed by multiple stenting of the coronary arteries with bioabsorptive scaffolds; the second stage was the hybrid treatment – femoral-tibial bypass with simultaneous recanalization and angioplasty of the lower leg arteries with good postoperative and long-term outcome.


908-916 98

The review focuses on the use of oral anticoagulants in fragile elderly patients. The issues of prevalence and diagnosis of senile asthenia syndrome or “fragility”, as well as its effects on the risks of thrombosis, bleeding and death, are discussed. The evidence base, which is quite limited, for the participation of fragile elderly patients in randomized controlled trials and real clinical practice trials with direct oral anticoagulants is presented. Nevertheless, one of the studies of real clinical practice showed that only therapy with rivaroxaban (out of three direct oral anticoagulants) compared with warfarin reduced the risk of stroke/systemic embolism and ischemic stroke alone in fragile elderly patients with atrial fibrillation after 2 years of observation.

917-921 81

The article discusses the current prevalence of hypercholesterolemia in everyday clinical practice in patients of different risk categories and approaches to its correction in the most frequently used clinical guidelines. High prevalence of hypercholesterolemia in practical health care with little change over time is shown. The existing problems of the practical implementation of the principles of a healthy lifestyle as the basis for reducing cardiovascular risk and possible solutions are described. Attention is focused on a low number of patients taking statins, and even less – reaching recommended target cholesterol levels. It is emphasized the validity of lower, compared to previous, target cholesterol levels in National recommendations on the correction of dyslipidemia in patients with proven atherosclerosis-related cardiovascular diseases as well as the feasibility in some cases of combined lipidlowering therapy (statins in combination with intestinal cholesterol absorption blockers, PCSK9 inhibitors, high doses of ethyl eicosopentaenoic acid). It is commented the need to prescribe statins in persons older than 75 years, but with a careful approach. Particular attention is paid to the use of statins in the primary prevention of cardiovascular complications. The validity of prescribing fixed moderate doses of statins for this purpose is discussed, which is both scientifically based and more realistic in practical terms.

922-934 170

The aim of this review was to present the recently published results of ODYSSEY OUTCOMES trial and discuss the clinical perspective of these data. Patients with acute coronary syndrome are at very high risk of recurrent ischemic cardiovascular complications, especially during the first year after the event. The use of high-intensity statin therapy in this group of patients does not always lead to the achievement of target levels of atherogenic lipoproteins. PCSK9 inhibitors, administered in addition to statins, can provide additional reduction of low-density lipoprotein cholesterol, which leads to further improvements of outcomes in patients with atherosclerotic cardiovascular disease. According to the latest results from ODYSSEY OUTCOMES trial, among patients with recent acute coronary syndrome, who were receiving high-intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who were treated with alirocumab then among those who received placebo. The treatment with alirocumab in patients with recent acute coronary syndrome was associated with reduction in death from any causes. The absolute risk reduction with alirocumab was the most prominent in the subpopulation of patients with low-density lipoprotein cholesterol ≥2,6 mmol/l at baseline. These results have implication for clinical practice and may play an important role for the improvement of outcomes in patients at highest cardiovascular risk after acute cardiovascular syndrome.

935-943 76

The possibilities of P2Y12 receptor inhibitors application in the treatment of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) are discussed in the article. The results of 4 registries in which a comparative analysis of the efficacy and safety of prasugrel with clopidogrel or ticagrelor was performed, as well as of all 3 P2Y12-receptor inhibitors among themselves, are considered in detail. The feasibility of replacing clopidogrel to prasugrel during the inpatient treatment of patients with ACS and PCI was evaluated additionally in the MULTIPRAC registry. The results of the registries demonstrate that the use of prasugrel in patients with ACS and PCI is associated with a significant reduction in the risk of ischemic complications and mortality with an acceptable risk of bleeding. At the same time, prasugrel was more effective and safer than clopidogrel and at least was non-inferior to ticagrelor, and according to some registries, even surpasses it in a number of indicators.



944-950 83

Review presents data on medicines from the new group of cardiovascular drugs, direct oral anticoagulants (DOACs) inhibitors, as antidotes for DOAC when stopping life-threatening bleeding. DOAC therapy is accorded by hemorrhages with lower frequency than therapy by indirect anticoagulants, but really exist. New antidotes for DOACs are idarucizumab, andexanet, ciraparantag. The need in antidotes for DOAC may suddenly appear in spontaneous bleeding, during surgical operation, invasive procedure, due to trauma, in patients with stroke, kidney or liver failure. Data is given on the frequency of the main types of bleeding while taking new oral anticoagulants. Information concerning use of antidotes for DOACs in bleedings as well as use of non-specific therapy are reviewed.


951-957 86
Aim. Investigation of comparative dissolution kinetics of generic medicinal products containing moxonidine versus reference drug. Material and methods. Objects of the research were film-coated tablets containing moxonidine (INN) in a dose 0.4 mg: a reference drug Physiotens® and 4 generic drugs. In vitro dissolution test of moxonidine from the study drugs was performed using comparative dissolution kinetics test (CDKT). The CDKT was performed in the media with the following pH: 1.2 (1:9 mixture of 0.1 M hydrochloric acid and water), 4.5 (acetate buffer solution, prepared as per State Pharmacopoeia, XIII), and 6.8 (phosphate buffer solution, prepared as per State Pharmacopoeia, XIII). The sampling for dissolved moxonidine was performed 5, 10, 15, 20, and 30 min after the test was started. An high performance liquid chromatography method with ultraviolet detection at 220 nm was used to assay. Results. Within 15 min more that 85% of moxonidine dissolved from the reference drug and all study drugs at pH 1.2; dissolution profiles were similar without calculation of similarity factor f2. Similarly, at pH 4.5 dissolution profiles of study drugs #2 and #3 were similar to that of the reference drug, and the similarity factor f2 was not calculated. However, in case of study drugs #1 and #4 significant differences were observed at a single time point (15 min), which suggests that their dissolution profiles are non-similar to that of the reference drug. Similarity factors f2 were calculated 17.52 and 35.30, respectively (less than 50). At pH 6.8 similarity factors f2 for all study generic drugs were also less than 50 (23.8, 49.8, 38.6, and 35.9), so their dissolution curves were non-similar to that of reference drug. Conclusion. In our study we observed difference in release in vitro of medicinal products containing moxonidines: none of the study drugs was fully similar to the reference drug in all media. The differences observed at pH 6.8 were noteworthy, where the samples had or faster kinetics (study drugs #2 and #3), or slower dissolution kinetics (test drugs #1 and #4). Observed differences in moxonidine release rate may impact absorption of active pharmaceutical ingredient into the blood following drug administration.



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