Rational Pharmacotherapy in Cardiology

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Vol 12, No 2 (2016)
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118-128 2728

Arterial wall status is determined by several characteristics, the main of them are as follows: pulse wave velocity (PWV), carotid arteries intima-media thickness (IMT), the presence of atherosclerotic plaques, endothelium-dependent vasodilation (EDVD). When these parameters change, the risk for cardiovascular disease (CVD) grows. The nature of relationship between these indices in people without CVD clinical signs is understudied, especially in those of older age.
Aim. To estimate correlations between different parameters of arterial wall in patients of different age without CVD.
Material and methods. A total of 303 people aged 25-91 years without any manifestations of CVD or other chronic diseases and without regular medical treatment were examined. PWV estimation, carotid ultrasound with IMT measurement and atherosclerotic plaques amount calculation and EDVD estimation using reactive hyperemia test were performed. Results. Patients without CVD clinical signs rather often reveal arterial wall lesions already in the younger age group (mean age 40.9±8.7): reduced EDVD – in 26% of the cases, the presence of atherosclerotic plaques – in 22%, increased PWV – in 15%, increased IMT – in 8%. The prevalence of arterial wall alterations in the older age group (mean age 61.19±8.5) increase many-fold. All arterial wall parameters correlate with age. The stronger correlation was revealed between IMT and the amount of atherosclerotic plaques: r=0.46 (р<0.001) in the younger group and r=0.47 (р<0.001) in the older one. We didn’t find any relationship between PWV and EDVD in the younger group and between PWV and the amount of atherosclerotic plaques in the older one. Thickened carotid intima-media increases the risk of arterial stiffness by 2.3 times.
Conclusion. Estimation of the state of arterial wall in people of young age without CVD allows detecting individuals who require active CVD prevention. Increased stiffness of arterial wall and the development of subclinical atherosclerosis represent different phenotypes of alterations.

129-137 1187

Aim. To study the association of depression with a high-sensitivity C-reactive protein (hsCRP) level, taking into account the main risk factors and noncommunicable diseases in Russia residents.
Material and methods. The data of ESSE-RF multicenter study (a representative sample of the unorganized male and female population aged 25-64 years from 8 regions surveyed in 2012-2014) were used in the work. A total 11884 people were involved into the study including 35.9% men. The examination included a survey on the standard questionnaire containing data on disease history, etc. The level of depression was assessed by the validated in Russian Hospital Anxiety and Depression Scale (HADS, 1983). hsCRP level was determined in all patients.
Results. The continuing association between elevated levels of depression (HADS-D ≥8+) and high level of hsCRP ≥3.0 mg/l (odds ratio [OR] 1.15; 95% confidence interval [CI] 1.03-1.27; p=0.009) was found in the multivariate model, after adjustment for sex, age, education, and risk factors. Reducing of the relationship of elevated levels of depression with a high level of hsCRP (OR 1.11; 95% CI 1.00-1.24; p=0.048) was found with the additional introduction of diseases in the model. This relationship was reduced to not statistically significant level (OR 1.08; 95% CI 0.98-1.20; p=0.134) in the full model adjusted for regions.
Conclusion. The reduced association of depression with hsCRP ajusted for aggregate risk factors was found in the study. This suggests about multifactor affecting on this relationship.

138-146 903

Aim. To investigate the prevalence of cardiorenal interactions, predictors of development, variants of clinical course, and outcomes of acute kidney injury (AKI) in patients with acute decompensation of chronic heart failure (ADCHF).
Material and methods. Patients (n=278) with clinical manifestations of ADCHF were included into the study. All patients underwent clinical, laboratory and instrumental investigation. Renal function was assessed using the CKD-EPI formula to calculate glomerular filtration rate (GFR). Hydration was assessed using the bioimpedance analyzer ABC-01 "Medass" (Russia). Chronic kidney disease (CKD) and AKI were diagnosed according to the criteria of the latest Russian and international guidelines. Six phenotypes of AKI were identified: outpatient and hospital acquired, transient and persistent, de novo, and on the background of CKD.
Results. CKD was detected in 125 (45%) patients. AKI developed in 121 (43.5%) patients, and in 52.9% of cases was nosocomial, in 53.7% transient and in 52.1% of cases occurred in patients without history of CKD. The risk of in-hospital mortality compared with patients without AKI significantly increased only in patients with nosocomial AKI (14.1 and 3.8%, p<0.05), AKI de novo (14.3 and 3.85%, p <0.05) and persistent (25 and 3.8%, p<0.001). Patients with these variants of AKI as compared to patients without AKI had more pronounced hydration, as well as less frequent prescription of loop diuretics and beta-blockers during outpatient treatment.
Conclusion. The high rate (67.6%) of cardiorenal interactions was found out in patients admitted to hospital with ADCHF. Unfavorable prognostic phenotypes of AKI were hospital acquired, persistent AKI and AKI de novo. Patients with these phenotypes had a more pronounced hydration and inadequate outpatient therapy.

147-153 922

Aim. To study the features of lipid-lowering therapy with rosuvastatin in high and very high cardiovascular risk patients in real outpatient practice.
Material and methods. Patients ≥30 years, visited internists or cardiologists of district outpatient clinics in the period from October 2013 to July 2014 were included into the study. Each patient fill in questionnaire. Determination of total cholesterol (TC) level was performed without special preparation of the patient using a portable photometric blood analyzer. Doctors prescribed rosuvastatin therapy when indicated, in accordance with the Guidelines, choosing the dose on their own. Repeated TC level was determined after 1 month.
Results. TC level was initially determined in 10547 patients. Rosuvastatin treatment was recommended for all patients. Repeated TC level determination was performed in 7897 patients in an average after 33 days. Baseline TC level in them was 6.37±0.89 mmol/l, and after 1 month while taking rosuvastatin – 4.89±0.81 mmol/l (p<0.001). The change of TC level was -22% (p<0.001). The average prescribed dose of rosuvastatin was 11.88±5.1 mg per day. The most often (62.8%) rosuvastatin was prescribed in a dose of 10 mg per day, in 27.3% of patients – 20 mg per day, in 9.2% – 5 mg per day, and only 0.5% of patients took it in the maximal dose.
Conclusion. In real clinical practice, rosuvastatin for treatment of patients with high or very high cardiovascular risk is often prescribed in moderate doses and rarely in the maximum dose despite the proven lipid-lowering effect.

154-159 1042

Aim. To study the remodeling of the left ventricle (LV) in patients with ST segment elevation (STEMI) and non-ST segment elevation (non-STEMI) myocardial infarction (MI). Materials and methods. Patients (n=99) with acute MI (48 – with STEMI, 51 – with non-STEMI) were examined. Diagnosis of MI was set on the basis of the dynamics of myocardial damage markers, data of clinical and electrocardiogram examination. The comparison group consisted of 33 patients with stable angina functional class 2. The control group included 35 healthy men. Structural and functional state of the LV myocardium and types of its remodeling were assessed by echocardiography.
Results. It was found that the LV eccentric hypertrophy was the predominated type of LV remodeling in patients with STEMI. Besides, these patients demonstrated disorders of the LV contractile function (LV ejection fraction 40.2±5.49% vs. 61.4±3.91% in control; p<0.05), the LV dilatation (end-systolic volume index 54.1±5.27 vs. 25.2±2.22 ml/m2 in the control; p<0.05), the lowest LV wall thickness (relative wall thickness 0.36±0.01 vs. 0.44±0.01 in control; p<0.05), increase in the LV myocardial stress (168.3±20.17 vs. 108.6±9.82 dynes/cm2 in control; p<0.05), and LV spherification. The majority of patients with non-STEMI revealed combination of concentric and eccentric types of LV remodeling. Their hemodynamic parameters were comparable to those in patients with stable angina, but exceed the control data.
Conclusion. In patients with acute MI severity of the LV remodeling correlated with the depth and vastness of myocardial damage. The most significant hemodynamic changes were observed in STEMI.

160-165 1406

Aim. To assess the efficacy of thrombolytic Fortelyzin in ST elevation myocardial infarction (STEMI) in real clinical practice.
Material and methods. Fortelyzin was administered intravenously to 38 patients with STEMI with follow-up assessment of reperfusion success by ECG and angiographic criteria. Bleedings, anaphylaxis and total mortality were considered.
Results. The ST-segment resolution up to 70% in 180 min was reached in 66% of patients and angiographic effect TIMI 2-3 – in 60% of patients. The major bleeding rate was 2.6%, allergic reactions – 0%, total mortality – 10.5%. Unsuccessful reperfusion was observed more frequently in patients with ECG ischemia of grade 3 and with angiographic visualization of the collateral blood flow.
Conclusion. The general efficacy of Fortelyzin in real clinical practice was 73%. ECG ischemia of grade 3 and the presence of angiographic collateral blood flow predict unsuccessful reperfusion of the infarct-related artery.

166-170 731

Actuality of cardiovascular diseases today determines the high interest to study pathogenesis of atherosclerosis and to searching new risk factors which could help to optimize primary and secondary prevention. Study the correlation between biomarkers of inflammation and traditional risk factors (TRF) in patients with different forms of ischemic heart disease is really important today.
Aim. To determine the correlation between TRF and the level of biomarkers of the inflammation and endothelial dysfunction in patients with acute coronary syndrome (ACS). Material and methods. Patients (n=62) aged from 24 to 50 years (mean age 43.98±4.73), who were admitted to the hospital due to ACS, were included into the study. Correlations between TRF and the levels of biomarkers of the inflammation and endothelial dysfunction were assessed. The following biomarkers levels were determined: high-sensitivity C-reactive protein (hsCRP), homocysteine, soluble vascular cell (sVCAM-1) and intracellular (sICAM-1) adhesion molecule type 1, soluble E-selectin (sE-selectin), nitrate, neopterin, matrix metalloproteinase type 3 (MMP-3).
Results. TRF, including modifiable ones, were often revealed in patients of the studied group. Some correlations between TRF and high concentrations of inflammatory biomarkers were determined. Patients with the family history of early cardiovascular diseases had higher concentration of sVCAM-1 (1047.78±516.98 ng/ml) in comparison with the patients without this TRF (705.57±239.28 ng/ml), p=0.017. Patients with arterial hypertension had higher level of MMP-3 (9.31±3.63 ng/ml) versus patients without hypertension (5.02±3.66 ng/ml), р=0.011). Patients with abdominal obesity compared with patients without this TRF demonstrated higher concentration of nitrate in acute (208.45±91.85 ng/ml vs 154.53 ng/ml, р=0.028) and long-term (193.53±40.02 ng/ml vs 173.48 ng/ml, р=0.028) periods of ASC.
Conclusion. The study showed the significant correlation between ТRF and high levels of some biomarkers of inflammation and endothelial dysfunctions in patients with ACS. So it is probably associated with more rapid progression of the atherosclerosis, higher risk of atherothrombotic events, complicated course of ischemic heart disease and unfavorable outcomes.

171-175 1508

Beta-blockers are an important part of modern pharmacotherapy in cardiology. The introduction of generics into clinical practice requires clear evidence of bioequivalence to the original drug.
Aim. To study the pharmacokinetics and effect on hemodynamic parameters of the original and a generic nebivolol in healthy volunteers in the fasting state. Material and methods. 18 healthy volunteers were included into the randomized open study on cross-balanced design. They received single dose (5 mg) of two compared preparations of nebivolol under fasting condition. The concentration of unchanged nebivolol in blood plasma was determined by gas chromatography-tandem mass spectrometry. Calculation of pharmacokinetic parameters and assessment of the hemodynamic were performed.
Results. The concentrations of nebivolol after the original and generic drugs intake did not differ significantly in any time point (AUC0-∞ 41.09±46.82 vs 47.16±66.58 ng•hr/mL and T1/2 30.84±10.78 vs 29.59±12.08 hours, respectively). Blood pressure reduction was slightly more pronounced when taking generic nebivolol, while the reduction in heart rate at 2 and 4 hours – after original nebivolol intake.
Conclusion. A comparative pharmacokinetic study of the genetic nebivolol showed its bioequivalence to the original drug. The effect on hemodynamic parameters with single dose (5 mg) of generic and original nebivolol in healthy volunteers was comparable.


176-179 779

Aim. To study the doctor awareness of the criteria of resistant hypertension (RHT) and to evaluate the features of the combination therapy of RTH patients in outpatient clinics. Material and methods. An analysis of medical records of patients with hypertension (n=1000) in 5 outpatient clinics in Moscow was made. A group of patients (n=126) with difficult to control hypertension 2-3 degrees, that internists considered as RTH, was specified. A survey of internists (n=78) of these outpatient clinics was also performed using a special questionnaire, which included questions on diagnosis and management of patients with RTH.
Results. 47% of doctors were not able to give a clear RTH definition. About 75% of internists prefer to increase the drug doses consistently in spite of its low initial efficacy. 20% of physicians used triple combination in the initial treatment of RHT. More than 40% of patients received not enough effective drug combinations.
Conclusion. Doctor awareness of RHT diagnostic criteria and management remained insufficient. RHT treatment is carried out with the use of not enough effective antihypertensive combinations and with low doses of drugs.


180-185 1158
Methods that allow to systematize the accumulated information on specifically formulated questions, analyze it and make reliable findings are of great interest and popularity with the emergence of a huge number of studies and publications in various fields of medicine, a significant increase in information, failure to identify weak effects in the individual studies. The use of systematic reviews and high-quality meta-analysis is an analytical basis of evidence-based medicine, it is a very valuable tool for decision-making at the level of practitioner, health care leaders and experts in the preparation of guidelines and legislation concerning the use of the most effective and safe treatments, when planning future research, in the development of rational health policy. Features of methods of systematic review and meta-analysis and their strengths and weaknesses are discussed in the article. The authors present the historical facts of occurrence of the Cochrane Collaboration, whose main task is to systematize and analyze accumulated information from a variety of medical research. The contribution of Russian researchers into this field of medical science is also assessed.


186-190 705
The interdisciplinary interim experts’ council on March 3, 2016 in Moscow have considered the EMPA-REG OUTCOME trial results and suggested a number of propositions and recommendations on further empagliflozin’s cardiovascular effects investigation and its clinical application in patients with type 2 diabetes at high cardiovascular risk.
191-195 2022
Up-to-date European approaches to the management of patients with atrial fibrillation (AF) after acute coronary syndrome and/or percutaneous coronary interventions are considered. Features of antithrombotic therapy in the early (hospital) and the delayed periods (up to 1 year after acute ischemic events) are discussed. The authors briefly present subanalysis of ARISTOTLE study, which compares the efficacy and safety of apixaban with these of warfarin in patients with atrial fibrillation and a history of ischemic heart disease.
196-203 842
Modern approaches to antiarrhythmic anti-relapse therapy of atrial fibrillation are considered. Advantages and disadvantages of the main therapeutic strategies are discussed from the standpoint of evidence-based medicine. The value of strategies of rhythm control, heart rate control and «upstream therapy» in the management of patients with atrial fibrillation is specified. Results of clinical studies on the efficacy and safety of anti-arrhythmic drugs, the search for such new drugs are presented. The authors state, that possibilities of modern drug therapy are limited, development and efficiency of other methods of anti-relapse therapy are low, new groups of drugs are not effective enough or are far from clinical applications. At that the adherence to treatment of patients with atrial fibrillation is unstudied, and its influence on the treatment outcomes, prevention of complications and long-term prognosis are ignored. Authors concluded that in conditions of limited capacity for drug therapy, evaluation of the effect of adherence to treatment in patients with atrial fibrillation, and elaboration on this basis the principles and tools of therapy, taking into account social and personal characteristics, are the most perspective directions of modern arrhythmology.
204-209 838
Review is devoted to the value of the use of highly sensitive troponin (hs-cTn) tests in the diagnosis of acute coronary syndrome. The classification of the Tn-tests depending on their sensitivity is presented. The possible reasons of troponins appearance in blood of healthy people are shown. Authors consider a 3-hour algorithm for myocardial infarction (MI) diagnostic, recommended by the expert group in 2012. Study results of 2011-2015 years are presented as the basis for the development of a one-hour MI diagnostic algorithm, recommended by the European Society of Cardiology in 2015. Authors discuss the results of studies showing that modern HS-cTnt tests (together with ECG assessment) are capable to diagnose MI in the early stages. They significantly increase the number of identified MI, especially MI without ST segment elevation, as well as identify the group of patients with subsequent favorable prognosis.


210-219 925
Pharmacotherapy of arterial hypertension in the elderly is discussed. Russian and international guidelines are presented with a focus on target levels of blood pressure and drugs of choice in these patients. Issues of efficacy and safety of antihypertensive therapy in patients aged 80 years and older are considered.
220-226 870
New oral anticoagulants that inhibit factor Xa (rivaroxaban, apixaban, edoksaban) or thrombin (dabigatran), today are increasingly replacing warfarin and other indirect anticoagulants in preventing stroke in patients with non-valvular atrial fibrillation. They were superior to warfarin for some indicators of efficacy and safety in randomized controlled trials. However, the experience of their study in real clinical practice is limited. The need in prospective, observational studies is dictated by the fact that usual practice differs from the conditions of the randomized clinical trials that may improve the efficiency and safety of the treatment, including the expense of strict criteria for patient selection, regular visits, constant safety monitoring and etc. The results of prospective observational XANTUS study and retrospective cohort studies that shown similar results of treatment with new oral anticoagulants in randomized clinical trials and routine clinical practice are presented in the review.
227-233 1431
Review of clinical studies showing the pleiotropic effect of vitamin D with a detailed description of pathogenetic ways to implement these effects  is presented. Relation of vitamin D with cardiovascular diseases, kidney diseases, disorders of the immune and nervous systems, aging is discussed according to results of current researches.
234-238 790
The role of endothelial dysfunction in the pathogenesis of ischemic heart disease and some other cardiovascular diseases is considered. The endothelial dysfunction takes place at the earliest stages of diseases. The interaction of vasodilator and vasoconstrictor factors produced by vascular endothelium is discussed. The treating effect of some medicinal products (nitrates, beta-blockers and others) is analyzed from the point of view of their correcting influence on endothelial function.

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