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Rational Pharmacotherapy in Cardiology

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Vol 14, No 2 (2018)
View or download the full issue PDF (Russian)
https://doi.org/10.20996/1819-6446-2018-14-2

ORIGINAL STUDIES

156-166 420
Abstract

Aim. To evaluate the economic burden of cardiovascular diseases (CVD) in the Russian Federation (RF) in 2016, including the direct costs and the economic losses caused by reduced productivity.

Material and methods. Main data sources: data of the Federal state statistics service, data of state statistical reporting (forms №14, №141, №12 and №16-VN), and data of State Guarantee Program of Free Medical Care to the Citizens of the RF, statistical data of CVD, ischemic heart disease (IHD), myocardial infarction, cerebrovascular diseases, stroke. The direct medical costs were calculated based on the number of hospitalizations, including daycare center, emergency calls and outpatient visits due to CVD using the costs of the State Guarantee Program. The amount of disability benefits payments was calculated based on the number of disabled persons from each group and by the amount of the disability allowance. Indirect costs (economic losses) included a shortage of gross domestic product (GDP) due to premature mortality and disability in economically active age and loss of earnings due to temporary incapacity for work. The potential years of life lost (PYLL) were calculated using the number of life years not reached in economically active age due to premature death. Losses associated with premature mortality in the economically active age included unproduced GDP due to lost life years in the corresponding age group due to deaths from CVD, meaning the population’ employment rate. Statistical analysis was performed by Microsoft Excel 10.0.

Results. PYLL due to premature death from CVD – 4.5 million years of potential life in economically active age, mostly men (3.3 million PYLL). Among almost 50% of men PYLL were due to ischemic heart disease. Economic burden because of CVD in 2016 in the RF reached 2.7 trillion ₽, which is equivalent of 3.2% of GDP for this year. In the structure of burden among all blood circulatory system diseases, IHD was in the first place (over 1 trillion ₽). In the burden structure, direct costs were only 8.1%, losses in the economics – 91.9% of the total burden. In the cumulative burden of CVD, IHD determined as 39.8% (over a trillion ₽), cerebrovascular diseases – fifth part (560 billion ₽), strokes and heart attacks – 424 billion ₽ and 213.1 billion ₽, respectively.

Conclusion. The economic burden because of CVD in the RF in 2016 was 2.7 trillion ₽ (3.2% of GDP). Economic losses caused by premature mortality of people in economically active age prevailed in the structure of the burden (over 90%). Such the significant economic burden is a weighty argument for increasing investments in the prevention and treatment of CVD.

167-175 242
Abstract

Aim. To perform pharmacoeconomic analysis of CHF therapy with supramolecular sacubitril/valsartan complex compared to routine therapy in patients with diabetes type 2 and ACE inhibitor intolerance within context of Russian healthcare system.

Material and methods. A Markov model based on Russian Standards of treatment and clinical practice results was built. Cost-effectiveness analysis was done by comparing two patient groups of 1000 people each. Budget impact analysis required 27,451 simulated patients. Randomized controlled clinical trials results of sacubitril/valsartan vs. routine practice were used as source of efficacy and safety data. Time horizon was set at 3 years. Quality Adjusted Life Years (QALY) were used as effectiveness. Single-factor sensitivity analysis (SA) was used to ensure the results are robust to changes in market situation.

Results. Cost-effectiveness ratio for sacubitril/valsartan is 301,145.7 rub. per QALY while cost-effectiveness ratio for routine practice is 510,621 rub. Budget impact analysis results indicate that during three years, in case of sacubitril/valsartan usage budgetary burden can be reduced by more than 220,000 rubles per patient and leads to savings of more than six billion rubles in terms of the whole population. Sensitivity analysis has confirmed the robustness of results.

Conclusion. These results indicate benefits of sacubitril/valsartan using for CHF patients with type 2 diabetes and ACE inhibitor intolerance and justify inclusion of this drug into reimbursement lists that allow to reduce risk of hospitalization, lethal outcomes and budget of healthcare system.

176-183 209
Abstract

Background. Levosimendan infusion can be used in the treatment of patients with acute decompensated heart failure (ADHF) with a reduction in cardiac output and signs of severe congestion/pulmonary edema.

Aim. To study impact of levosimendan on renal function in patients with ADHF with reduced systolic function.

Material and methods. The study was a prospective, randomized trial. We enrolled 30 men (age 62.5 [55.8-69.3] years) hospitalized with ADHF with reduced systolic function (left ventricular ejection fraction <40%), increased level of brain natriuretic peptide (BNP>500 pg/mL) and systolic blood pressure >125 mmHg. All patients were randomized into 2 groups of 15 people each. In the first group, the patients received an intravenous infusion of levosimendan 0.1 μg/kg/min for 24 hour added to standard therapy. The second group received standard therapy.

Results. 24-hour levosimendan infusion significantly increased the glomerular filtration rate levels from 65.4 [45.2-99.2] mL/min/1.73m2 at baseline to 79.0 [66.3-93.1] mL/min/1.73m2 at discharge (p= 0.011), greatly decreased serum creatinine from 1.17 [0.90-1.55] mg/dL at baseline to 1.01 [0.89-1.14] mg/dL at discharge (p = 0.009) and blood urea nitrogen and at the same time improved renal blood flow in patients with ADHF while there were no clinically significant changes in the studied parameters in the standard therapy group.

Conclusion. Levosimendan had a positive effect on renal function in patients with ADHF with reduced systolic function.

184-189 155
Abstract

Aim. To study the erythrocyte electric charge (EEC) in patients with metabolic syndrome (MS) depending on glycemia levels. Material and methods. 112 patients (45 men and 67 women, age 61.4Ѓ}7.2 years) with MS (MS duration 8.7Ѓ}5.2 years) were studied. EEC level 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. All statistical analyses were done using Statistics 10.0 software.

Results: Abdominal obesity was registered in 100% of patients, hypertension – in 73%, fasting hyperglycemia – in 75%, dyslipidemia – in 80% of patients. Mean glycated hemoglobin (HbA1c) level in patients with MS was 7.3Ѓ}1.9%. The mean EEC level in group of MS patients (1.59Ѓ}0.05×107) was significantly lower than in the control group (1.67Ѓ}0.03×107), p<0.05. In patients with MS and fasting hyperglycemia the EEC levels were significantly lower than in those without fasting hyperglycemia (1.58Ѓ}0.05×107 vs 1.64Ѓ}0.03×107, respectively, p<0.001). Significant negative correlations between EEC and age (r=-0.43, p<0.05), average duration of MS (r=-0.87, p<0.05), average plasma glucose concentration (r=-0.6, p<0.05), average duration of fasting hyperglycemia (r=-0.83, p<0.05), and blood HbA1c level (r=-0.56, p<0.05) were found in patients with MS.

Conclusion: Significantly lower values of EEC are observed in MS patients with increasing age, duration of MS, and duration of hyperglycemia. Negative correlation between HbA1c and EEC was also shown.

190-196 192
Abstract

Aim. To study the effectiveness of achievement of lipid profile target levels and safety of therapy with atorvastatin in different doses in patients with acute ST-segment elevation myocardial infarction (STEMI).

Material and methods. The open prospective controlled single-center study included 90 patients with STEMI aged 32 to 65 years. In the first 24-96 hours from the disease onset the patients were randomized into two groups: the first group included 43 patients who received high-dose statin therapy – atorvastatin 80 mg/day (Group 1), the second group (Group 2) – 47 patients receiving atorvastatin 20 mg/day. Examination of patients with STEMI included the assessment of plasma lipid profile, blood levels of hepatic transaminases, creatine phosphokinase (CPK), C-reactive protein (CRP), brain natriuretic peptide (BNP), creatinine, glucose and glomerular filtration rate calculation.

Results. A decrease in the level of low density cholesterol (LDC) by 52.4% (p<0.001) was found after 24 weeks in Group 1. Achieving the target LDC level was found in 46% of patients and a decrease of LDC>50% from the baseline – in another 26%. LDC decreased by 33% in Group 2 (p<0.001). Achieving the target LDC level was found in 17% and a decrease of LDC>50% – in 15% of patients. After 24 weeks, a statistically significant decrease in hepatic transaminase activity was found in the both groups in comparison with the baseline level. The level of CRP decreased 9.1 times (p<0.001) in Group 1, and 7.8 times (p<0.001) – in Group 2. Reduction in the level of BNP was also found in Group 1 by 60% (p=0.005), and in Group 2 – by 33.8% (p<0.001). The levels of CPK, creatinine and GFR in the both groups did not change. A comparable decrease in fasting glycemia was found after 24 weeks in the both groups.

Conclusion. The revealed lipid-lowering and pleiotropic effects confirm the necessity of using atorvastatin 80 mg. The absence of changes in the level of transaminases, CPK, serious adverse effects indicates the safety of the use of high-dose statin therapy in STEMI patients for the secondary prevention of cardiovascular events.

197-203 221
Abstract

Background. Monitoring of serum digoxin concentration (SDC) is one of the approaches for controlling the safety of the long-term digoxin treatment, however, the benefits from SDC monitoring in paroxysmal arrhythmias have not been studied.

Aim. To evaluate the potential benefits of digoxin laboratory monitoring at the initiation of digoxin therapy in patients with paroxysmal atrial fibrillation (AF).

Material and methods. A retrospective analysis of SDC was performed in patients with paroxysmal or persistent (n=142) and permanent AF (n=48) who received digoxin therapy. Anthropometric features, comorbidity, anamnesis of the underlying disease, concomitant therapy, severity of signs of myocardial remodeling and the presence of cardiac rhythm and/or conduction disorders before and after the treatment were considered to analyze the results of treatment. SDC was measured in 20 hours after digoxin treatment initiation and after restoration of sinus rhythm, or in 1 week after the start of therapy if arrhythmia persisted.

Results. During the first week after digoxin therapy initiation the rate of non-specific ECG repolarization abnormalities was 54%, the incidence of clinically significant conductivity disturbances – 28%. We found a relationship between SDC in the first week of treatment and the risk of high grade AVor SA-conduction abnormalities after the restoration of sinus rhythm (mean SDC 0.98Ѓ}0.72 ng/dL in the group of patients with complications and 0.45Ѓ}0.42 – in the group without them, p=0.015); these complications did not correlate with clinical signs of digitalization or intensity of digoxin therapy. The intake of digoxin was not an independent factor for the occurrence of cardiac rhythm disturbances. Comparison of the direct SDC measurements and the calculated values obtained with the valid calculators developed for the long-term digoxin use did not show reliable reproducibility of the calculated data.

Conclusion. SDC monitoring may be used during the first week of therapy (before the establishment of a steady-state SDС) to minimize the risks of clinically significant adverse effects of digoxin on intracardiac conduction at the start of therapy. The existing empiric SDC calculators are not suitable as an alternative to the direct measurement. Further studies are needed to determine the clinically valid borderline values of the safe SDC in the condition of rapid digitalization.

204-209 152
Abstract

Aim. To identify most probable cardiovascular predictors of periprocedural ischemic brain microlesions after carotid artery stenting (CAS) accounting its presumable pathogenesis.

Material and methods. 84 patients with carotid artery stenosis undergoing CAS in a specialized medical center were examined. Diffusion-weighted imaging (DWI) magnetic resonance imaging was performed in all patients before and after intervention.

Results. Among selected patients aged 40 to 83 years (mean age of 60.6Ѓ}3.9 years, male 80.95%) 39 (46.4%) patients had new ischemic brain microlesions after CAS, differently located. Among all patients (n=84) microlesion count correlated with age (γ=0.243; p<0.01), preprocedural hemoglobin level (γ=-0.278; p<0.01), systolic blood pressure (SBP) level before CAS (γ=0.190; p<0.05) and diastolic blood pressure (DBP) level 1 hour after CAS (γ=-0.201; p<0.05). In patients with microlesions their count (n=39) correlated with SBP and DBP levels 15 min after CAS (γ=-0.370; p<0.01 and γ=-0.369; p<0.01, respectively), percentage of SBP and DBP levels decrease during CAS (γ=0.404; p<0.01 and γ=0.458; p<0.001, respectively), SBP level 24 h after CAS (γ=-0.272; p<0.05) and body mass index (γ=-0.260; p<0.05). Patients with multiple microlesions (n=25) differed from patients without lesions (n=45) older age (67.0 [64.0; 77.0] vs 64.0 [60.0; 70.0], p<0.05), lower preprocedural hemoglobin level (130.9Ѓ}14.5 vs 139.5Ѓ}13.6, p<0.01), lower percentage of smokers (32.0% vs 57.8%, p<0.05), previous ipsilateral stroke (36.0% vs 13.3%, p<0.05) and persistent periprocedural arterial hypotension (12.0% vs 2.2%, p<0.05). These patients with multiple microlesions had more significant DBP level decrease (17.0 [10.0; 25.0] vs 6.5 [1.3; 11.8], p<0.05) compared with patients with single lesions (n=14). In the group of patients with single brain microlesion, unstable (71.4% vs 40.0%, p<0.05) and calcified (64.3% vs 28.0%, p<0.05) atherosclerotic plaques were seen more often compared with patients with multiple lesions. Patients with single brain microlesion differed from patients without lesions greater frequency of calcified atherosclerotic plaques (64.3% vs 31.1%, p<0.05), usage of proximal embolic protection devices (21.4% vs 0.0% p<0.01) and predilatation (35.7% vs 13.3%, p<0.05), perioperative neurological symptoms (21.4% vs 4.4%, p<0.05, and higher SBP levels during 24 h after CAS (mean values 137-122 mm Hg vs 120-112 mm Hg, p<0.05).

Conclusion. Single microlesion is associated with unstable or calcified plaques and CAS technical complexities. Multiple microlesions may be associated with periprocedural hemodynamic instability and cerebral hypoperfusion risk factors.

210-216 252
Abstract

Aim. To study the effects of sacubitril/valsartan on left ventricular-arterial coupling (LVAC) and arterial stiffness in HFrEF patients.

Material and methods. Arterial stiffness by applanation tonometry and LVAC – by two-dimensional echocardiography were evaluated in 18 patients with compensated HFrEF (age 69Ѓ}9 years, 89% male, arterial hypertension – 83%, diabetes – 39%, myocardial infarction – 89%, left ventricular ejection fraction 32Ѓ}4%) initially and after 6 and 12 months of therapy based on sacubitril/valsartan. LVAC was calculated as the Ea (arterial elastance)/ Ees (left ventricular elastance) ratio. Differences were considered statistically significant at p<0.05.

Results. 72% of patients initially had elevated pulse wave velocity (PWV>10 m/s). The decrease in PWV (from 11.5Ѓ}2.9 to 10.2Ѓ}2.9 m/s, p<0.05), of the augmentation pressure (from 15.3Ѓ}8.9 to 10.5Ѓ}5.0 mm Hg, p=0.002), the increase in the reflected wave transit time (from 132Ѓ}9 to 143Ѓ}29 ms, p=0.02) and the subendocardial viability ratio (from 164Ѓ}25 to 177Ѓ}37%; p=0.009) were found after 12 months. Sacubitryl/valsartanbased therapy was associated with a decrease in central systolic blood pressure (from 116Ѓ}19 to 106Ѓ}10 mm Hg; p=0.001) and central pulse blood pressure (from 44Ѓ}15 to 38Ѓ}7 mm Hg; p<0.05). Decrease in Ea (from 2.20Ѓ}0.84 to 1.79Ѓ}0.63 mm Hg/ml/m2; p=0.005) and Ea/Ees ratio (from 2.26Ѓ}0.77 to 1.68Ѓ}0.32, p=0.05) was found after 12 months. Ees did not change statistically significantly (1.00Ѓ}0.34 vs 1.01Ѓ}0.44 mm Hg/ml/m2). The relationship between the decrease in PWV, Ea and the dynamics of blood pressure was not found.

Conclusion. Sacubitryl/valsartan-based therapy in HFrEF patients results in a BP-independent improvement in LVAC due to a decrease in Ea, an improvement in the parameters of the central pulse wave.

217-222 221
Abstract

Aim. To study the effect of long-term combined antihypertensive therapy with lisinopril plus amlodipine on the parameters of central aortic pressure (CAD) and visceral obesity in patients with arterial hypertension (HT) combined with type 2 diabetes mellitus (DM).

Material and methods. 30 patients with stage III of HT and DM type 2 aged 40-65 years were included into the study. After "washout period", combined therapy with amlodipine 6.2Ѓ}2.5 mg/day and lisinopril 12.3Ѓ}5.0 mg/day was prescribed, hypolipidemic therapy with atorvastatin 17.0Ѓ}4.7 mg/day and combined hypoglycemic therapy with metformin 1093.8Ѓ}253.6 mg/day and gliclazide 82.1Ѓ}38.5 mg/day were continued within 24 weeks. Initially, and after 24 weeks, a standard physical examination, 24-hour CAP parameters monitoring, body composition analysis with a percentage of visceral fat calculation, a visceral fat index (VAI) determination, the degree of adipose tissue dysfunction and the level of glycated hemoglobin (HbA1c) assessment were performed.

Results. Because of long-term therapy with lisinopril + amlodipine, a significant decrease in the level of office systolic (SBP) and diastolic blood pressure (DBP) by 22.3 and 12.5%, respectively, heart rate by 9,8%, and HbA1C level by 1.4% was found in comparison with the initial values. According to bioimpedanceometry a statistically significant decrease in the percentage of visceral fat (by 13.6%) was revealed, as well as VAI (by 22.5%) and the percentage of patients with very high visceral fat (Δ%=-36.7, р<0.05). Indicators of central hemodynamics were significantly improved in the form of decrease in the average daily, daytime and nighttime values of aortic SBP, DBP, pulse blood pressure, and augmentation index.

Conclusions. Thus, long-term combined therapy with lisinopril and amlodipine has shown not only high antihypertensive efficacy and the ability to reliably improve the parameters of CAD, but also to reduce the activity of visceral obesity, providing an additional positive metabolic effect without adjusting the dose of statins and hypoglycemic drugs.

ASSOCIATED PROBLEMS OF CARDIOLOGY

223-228 184
Abstract

Aim. To investigate the dynamics of biomarkers of early renal damage in patients with hypertension (HT) and obesity treated with lisinopril and diet therapy.

Material and methods. The study included 120 people aged 25 to 55 years (90 patients with HT in combination with obesity and 30 HT patients without obesity). Control group was consisted of 50 healthy respondents without obesity. All HT patients received therapy with lisinopril at a dose of 10-40 mg per day with titration to target blood pressure (BP) values, patients with obesity – additionally diet therapy. Initially and after 6 months we investigated clinical and biochemical parameters, levels of leptin, resistin, cystatin C in blood serum and urine, albuminuria, NGAL (neutrophil gelatinase associated lipocalin) and interleukin 18 (IL-18) in the urine.

Results. We identified the relationships between the serum cystatin C and BP, leptin, resistin, insulin-resistance index (HOMA-IR) and also metabolic indicators. In this study we revealed relationships of subclinical tubular dysfunction markers (urinary cystatin C, IL-18, NGAL) with carbohydrate and lipid metabolism, BP, hormonal activity of adipose tissue. The achievement of target BP values, normoalbuminuria and improving the glomerular filtration rate (GFR) were found after 6 months. The decrease in serum cystatin C in groups was seen: in Group 1 – from 1112 [757.0; 1400.0] to 797 [754; 825] ng/ml (р=0.001), in Group 2 – from 990 [700.0;1110.0] to 791 [770;900] ng/ml (р=0.03). Decrease in markers of tubular dysfunction was identified only in patients who reduced the body weight: urine cystatin C − from 33.0 [18.5; 50.0] to 24[15.3; 60.0] ng/ml (р=0.04) and IL-18 – from 0.33 [0.18; 0.41] to 0.21 [0.14; 0.43] pg/ml (р=0.04). Greater reduction in tubular dysfunction markers excretion was observed in the subgroup of patients with weight loss more than 5% but less than 10% of the initial value.

Conclusion. The obtained relationships between markers of subclinical tubular damage and carbohydrate, lipid metabolism and adipokines prove the contribution of adipose tissue to the formation of tubular damage in patients with HT associated with obesity. Antihypertensive therapy with lisinopril contributes to the achievement of target BP values, improvement of metabolic parameters, increase in GFR, achievement of normoalbuminuria, whereas body weight loss in HT patients with obesity additionally contributes to the reduction in the manifestations of tubular dysfunction.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

229-234 181
Abstract

Aim. To study the awareness and opinion of patients with atrial fibrillation (AF) about the stroke prevention.

Material and methods. This study based on the questionnaire survey of 544 patients from three regions of Russia is the third part of the PRIMA-TERRA register. The survey was carried out in the period from 01.12.2012 to 01.07.2013 by independent employees on a special questionnaire of 9 questions. The ratio of men and women was 42% vs 58%, respectively, the average age was 65.6Ѓ}8.2 years. The AF duration was 7.6Ѓ}2.0 years. The average score of CHA2DS2-VASc was 3.4Ѓ}1.4.

Results. Less than 70% of patients were informed of possible AF complications, of which less than a third – about the risk of stroke. Only 62% of patients believed that they take drugs for the stroke prevention, of which only 31% took warfarin, 15% new oral anticoagulants (NOAC). The majority of patients received antiplatelet agents and their combinations – medications not recommended for this purpose by modern National and European cardiology guidelines. Less than 60% of the respondents were informed about the NOACs, while clinically significant information about the benefits of this group of drugs was provided by doctors only to 18% of patients. The main reason limiting the widespread use of NOACs is the high cost of these drugs.

Conclusion. Awareness of patients about AF thromboembolic complications is extremely inadequate. For the prevention of stroke, most patients take antiplatelet agents and their combinations, less than a half – anticoagulants. The main reason for refusing to receive the NOACs is the high cost of this group of drugs.

235-243 187
Abstract

Aim. To study the doctors' opinions on the main aspects of antiplatelet agents use, and to test their knowledge of the basic provisions of the current recommendations on antiplatelet therapy.

Material and methods. As a material for the study the results of an anonymous questionnaire in randomly selected doctors were used. The questionnaire contained 11 questions concerning the use of antiplatelet agents for primary and secondary prevention of cardiovascular diseases. 276 questionnaires filled out by 185 therapists, 84 cardiologists and 7 physicians of other therapeutic specialties were analyzed.

Results. The results of the study reflect the doctor’s tendency to use acetylsalicylic acid for the primary prevention of cardiovascular diseases, including the patients who do not have indications for its prescribing. 11.6% of respondents never recommend acetylsalicylic acid for primary prevention of cardiovascular diseases. 22.8% of doctors don’t consider it necessary to stop acetylsalicylic acid in patients who do not have indications for such treatment. Therapists demonstrate very low adherence to recommendations which underline the need for a weighted approach to the acetylsalicylic acid prescription. Cardiologists less often than therapists recommend acetylsalicylic acid for the primary prevention of cardiovascular disease in patients with low cardiovascular risk. Less than 30% of therapists and cardiologists tend to prescribe gastroprotectors to patients with aspirin-induced gastropathy. Only 19.6% of the respondents correctly indicated the P2Y12 receptor inhibitor dose to be used in combination with acetylsalicylic acid on the 1st day of acute coronary syndrome depending on planed treatment strategy. 88.4% of doctors consider the use of antiplatelet agents, if the patient with atrial fibrillation and a high risk of thromboembolism refused to take oral anticoagulants. 51.8% of respondents recommend a combination of acetylsalicylic acid and clopidogrel for such patients. Cardiologists are better informed about the recommendations regarding the use of dual antiplatelet therapy and a combination of antiplatelet agents with oral anticoagulants. However, in general, doctors' knowledge of combined antithrombotic therapy is inadequate.

Conclusion. The results of the study show that it is necessary to discuss current recommendations on the use of antiplatelet agents for the primary and secondary prevention of cardiovascular diseases in the context of continuous medical education more actively.

244-251 167
Abstract

Aim. To assess five-year trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina on the level of out-patient specialized healthcare institution in Moscow.

Material and methods. Two-stage retrospective pharmacoepidemiological study was conducted. The object of the study – patient medical records. At the first stage of the study medical records of 2915 patients with stable angina visited the healthcare institution for the first time in 2006 were included, at the second stage – medical records of 1633 patients with stable angina with primary visit in 2011.

Results. Over the five-year period prescription rates of drugs improving prognosis in patients with stable angina significantly increased: antiplatelets – up to 82.7%, beta-blockers – up to 74.3%, statins – up to 45.6%. Despite of no changes registered in prescription rate of the ACE inhibitors, marked increase up to 14.7% in prescription rate of angiotensin receptor blockers was revealed. In the prescription structure of pharmacological groups changes were detected concerning the preferred choice of a specific drug. Due to implementation of dual antiplatelet therapy into clinical practice a reduced number of recommendations of acetylsalicylic acid as monotherapy (down to 93.0%) and increased – in combination with clopidogrel (up to 5.4%) was registered at the second stage of the study. Over a five-year period bisoprolol (55.0%) occupied the leading position in the group of beta-blockers. Metoprolol’s prescription rate decreased to 27.4%. Prescription rate of atenolol decreased down to 3.1%, while that of nebivolol increased up to 8.3%. When choosing among statins specialists recommended significantly more often atorvastatin (up to 52.9%). In the group of ACE inhibitors three drugs preserved their leading positions. Meanwhile the number of recommendations of enalapril increased up to 50.8%, perindopril – up to 24.1%. Analysis of prescribed doses revealed significant increase in recommendations of specific drugs in higher daily doses: acetylsalicylic acid 100 mg – up to 71.1%, simvastatin and atorvastatin 20 mg – up to 60.5% and 41.9%, respectively. When prescribing beta-blockers and ACE inhibitors specialists continued to use minimal and medium therapeutic doses, possibly due to dose titration in patients with comorbidities.

Conclusion. Study results demonstrated positive trend in terms of specialists’ adherence to guidelines on secondary prevention of cardiovascular diseases in patients with stable angina. However, a number of problem aspects were identified that require further optimization of medical and preventive measures in healthcare institutions.

252-259 171
Abstract

Aim. To study regional features and preferences of specialists in the choice of drug therapy of arterial hypertension in four subjects of the Far Eastern Federal District.

Material and methods. Statistical data, demographic indicators, state and municipal drug procurements in Chukotka Autonomous Okrug, the Sakha Republic (Yakutia), the Magadan Region, and Kamchatka Krai were analyzed. The studied period was 2012-2016. Dynamics of the use (procurements) of five main therapeutic classes of antihypertensive drugs was studied.

Results. Among β-blockers the leaders were metoprolol (from 2% to 30.8%) and bisoprolol (from 2.4% to 20.3%); in group of angiotensin converting enzyme inhibitors – enalapril (from 3.6% to 27%), lisinopril (from 4.4% to 23.9%) and perindopril (from 0.9% to 7.8%); among calcium channel blockers – amlodipine (from 5.6% to 11.3%); in group of diuretics – indapamide (from 2.5% to 13%) and spironolactone (from 3% to 12.5%), and in group of angiotensin II antagonists – losartan (from 0.4% to 15.6%). Angiotensin converting enzyme inhibitors were the most used therapeutic class of antihypertensive drugs in Chukotka Autonomous Okrug, the Magadan region and Kamchatka Krai. At the same time, β-blockers accounted for more than a half of state and municipal procurements in the Sakha Republic (Yakutia).

Conclusion. It is necessary to study regional aspects and approaches to therapy to assess the extent and specificity of the implementation of research results, standards and recommendations in real clinical practice.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

260-265 196
Abstract

Aim. To assess long-term outcomes in patients after acute stroke within LIS-2 registry.

Material and methods. 960 patients hospitalized in 2009-2011 due to acute stroke in one of the district hospitals of Lyubertsy town were included into analysis. The first assessment of the life status was carried out in 2012-2013 through 2.8 [2.1; 3.5] years after discharge, and a reassessment was in 2017 through 7-8 years after discharge, median follow-up 6.1 [6.9; 7.7] years. The primary endpoint was total mortality. Survival was assessed using the Kaplan-Meier curves.

Results. Only 300 patients were alive by the end of the follow-up, 543 patients died, and life status of 117 patients were unknown. Kaplan-Mayer curves showed that mortality was the highest during the first year after stroke, and then it stabilized and remained unchanged till the end of the followup. Less than a third of patients were alive after 8 years of follow-up. The identification of causes of death was difficult in a significant number of cases (in 52% of cases the cause was unknown). Acute stroke and other cerebrovascular diseases, as causes of death, were found in 15% of deaths, other cardiovascular diseases – in 18%, oncological diseases – in 7%, injuries – in 4%. Such causes of death as acute myocardial infarction, pulmonary disease or pulmonary embolism accounted for only 2% in the structure of deaths. A trend towards decrease in the proportion of recurrent stroke as the cause of death was observed as the follow-up period increases.

Conclusion. Mortality rate of patients after acute stroke remains stably high throughout the follow-up period: after 8 years less than a third of patients were alive. Death from acute stroke and cardiovascular diseases prevailed among the main causes of death at a distant stage of observation. It is necessary to analyze the factors determining the long-term outcomes at different periods after the stroke.

INNOVATIVE CARDIOLOGY

266-271 303
Abstract

In 2016, according to the Ministry of Health of the Russian Federation, about 200 thousand people died from stroke. Strokes are considered as the main cause of disability of the population, causing huge economic damage to the country. One of the most common causes of ischemic stroke is atherosclerosis of the branches of the aortic arch. The most common localization of atherosclerotic plaques is the extracranial section of the carotid arteries – bifurcation and ostium of the common carotid artery and the internal carotid artery. Recanalization of occlusion of the internal carotid artery until recently was an insoluble task for interventional surgery due to the high risk of distal embolization. The invention and use of the proximal cerebral protection device, which ensure the complete cessation of blood flow, has changed the situation. Effect of carotid revascularization on arterial hypertension, due to the effect on the baroreceptors of the carotid plexus by balloon angioplasty, which leads to a reflex decrease in arterial pressure, is an additional advantage of the endovascular technique in some cases. This effect requires further study. One also needs to pay careful attention to the diagnosis and imaging of carotid artery lesions before procedure. This clinical case is the illustration that an adequate assessment of the risk factors for intraoperative complications allows to achieve maximum results of endovascular treatment.

POINT OF VIEW

272-283 206
Abstract

Atherosclerotic peripheral artery disease (PAD) is well-known thrombotic risk factor in different cohorts of patients. This current review analyzes epidemiological data of trials and registries about influence both clinical and asymptomatic peripheral atherosclerotic disease on adverse ischemic events. Individual assessment of the atherothrombotic prevalence, which is directly related to vascular thrombotic risk, remains an important problem. Issue of PAD routine screening using traditional methods of ultrasound duplex scanning, measurement of ankle-brachial index is discussed in details. Comparative efficiency of present antiplatelet and anticoagulant drugs is shown in the key of preventing PAD thrombotic complications. PAD detection can be the reason for "intensification" of antithrombotic treatment, the only one option of which until recently was an additional treatment with P2Y12 platelet receptors blockers. However, the routine treatment with dual antiplatelet therapy in stable manifestations of atherothrombosis is not supported by the current guidelines. In this regard, it seems relevant to intensify therapy by simultaneously affecting on the platelet and plasma components of hemostasis in patients with PAD, that was demonstrated in a recently published study COMPASS. Treatment with rivaroxaban small doses in addition to acetylsalicylic acid allowed to improve significantly outcomes in a wide range of patients with stable manifestations of atherothrombosis without high risk of bleeding and severe renal impairment. However, use of this multicomponent therapy has not been approved by relevant clinical recommendations yet, which causes certain difficulties in choosing optimal scheme of antithrombotic treatment among patients with PAD.

284-291 168
Abstract

The aim of the review is presenting the possibilities and perspectives of the third generation of thienopyridine P2Y12 receptor inhibitor prasugrel in the treatment of patients with acute coronary syndrome (ACS). The main pathogenetic stage of ACS is intracoronary thrombosis, which develops on the surface of a damaged atherosclerotic plaque. The use of acetylsalicylic acid with addition of the second antiplatelet agent, so-called dual antiplatelet therapy, is a standard component in the treatment of any type of ACS, regardless of reperfusion and the selected treatment strategy. Due to some limitations in the use of clopidogrel as the second component of dual antiplatelet therapy, the possibility of prasugrel or ticagrelor usage should be considered in patients with ACS with percutaneous coronary intervention (PCI). Prasugrel therapy is associated with better clinical outcomes as compared with clopidogrel therapy in moderate or high-risk patients who undergo PCI. Because of higher bleeding risk and the lack of clinical benefits in special subgroups of patients, prasugrel must not be used in patients with a stroke or transient ischemic attack in the past. If, after a thorough individual benefit-risk assessment a decision is in favor of prescribing prasugrel to the patient older than 75 years or with a small body weight the maintenance dose of prasugrel is to be reduced by half. Real clinical practice data has shown that with following these recommendations prasugrel demonstrates optimal efficacy, safety, and even more significant impact on the prognosis than this in clinical trials. Prasugrel is able to reduce significantly the incidence of cardiovascular events such as cardiovascular death, myocardial infarction and stroke in patients with ACS who undergo PCI.

292-297 182
Abstract

Aim. To study the clinical and economic advantages of patient-oriented treatment in comparison with the traditional treatment of polymorbid patients with hypertension according to the secondary combined end point (benefit) and the primary end point (total mortality).

Material and methods. A change in the "advantage" index and total mortality in patient-oriented treatment (n=500) and traditional treatment (n=500) were studied in a cohort study in 1,000 polymorbid patients with hypertension.

Results. The change in advantage was related to the intensity of the response of the starting therapy and the effectiveness of its subsequent modification based on an assessment of the respondents' initial adherence to treatment, rather than the class or cost of medicines, the original or generic nature of the drugs, or their dosage frequency. The patient-centered approach, based on active feedback, demonstrated advantages over traditional treatment. The principle of estimating the "cost of living in effective rubles" has shown that in patient-oriented treatment, even with an increase in the direct costs of pharmacotherapy, clinical improvement with a reduction in overall mortality ensures greater treatment benefits than traditional therapy. The initial advantage of treatment was 4.22 and 4.28 effective rubles, by the 100th week of the study – 3.08 and 4.09, and by the 200th week – 2.75 and 3.75 rubles, respectively. The mortality rate for 200 weeks was 3.8% in the first, and 5.4% in the second subsample (p=0.017).

Conclusion. The analysis of advantage can be a step towards resolving the "conflict of interests" of the subjects of medical care. The introduction of clinical advantage assessment in medical practice allows a practical doctor to substantiate the clinical and economic feasibility of a specific therapeutic regimen, including the selection of a commercial nomenclature of medicines.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

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Abstract

Large randomized clinical trials (RCTs) in patients with non-valvular atrial fibrillation (AF) showed that new direct oral anticoagulants (DOACs) were just as effective at preventing stroke and systemic thromboembolic (STE) complications as warfarin, although DOACs were associated with less risk of intracranial bleeding. There was significant increasing number of publications addressed to use of DOACs in real-world setting in recent years. We discussed some of pros and cons for studies used real-world data in the review. Results of real-world studies provided a generally strong support for conclusions of main RCTs. In comparison of different DOACs against each other apixaban demonstrated lower bleeding risk while patients given rivaroxaban appeared to have higher rate of hemorrhagic events. High adherence to apixaban treatment for AF irrespective to additional value educational program suggested that apixaban treatment is easy to follow and well accepted by patients despite of twice-daily dosing regimen. Healthcare cost analyses demonstrated that patients who were prescribed apixaban had lower stroke/STE-related as well as major bleeding-related medical costs.



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