Rational Pharmacotherapy in Cardiology

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Vol 12, No 3 (2016)
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244-252 559
Detection of principal subclinical arterial wall lesions is one of the most important aspects of effective cardiovascular disease (CVD) primary prevention. Such lesions include: arterial wall thickening, increased rigidity, endothelial dysfunction development. However, the role of traditional CVD risk factors in the development of individual arterial wall lesions in CVD-free people is understudied. This is particularly so with people of older age. Aim. To study the role of traditional CVD risk factors in development of arterial wall lesions in relatively healthy individuals of different age. Material and methods. We have examined a total of 303 people aged 25-91 years, with no signs of CVD and other chronic diseases and without any regular medical treatment. Anthropometric parameters, blood pressure, fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides levels were detected in all the patients. Measurement of pulse wave velocity was conducted using SphygmoCor device (AtCorMedical,Australia). Carotid ultrasound to measure intima-media thickness and number of atherosclerotic plaques was conducted using linear transducer with ultra-high resolution 17-5 MHz (PHILIPS iU22, the Netherlands) in the B-mode. Endothelium-dependent vasodilation was assessed by the reactive hyperemia test. Results. Multivariate linear regression analysis has revealed fasting hyperglycemia and increased systolic blood pressure to be to a greater degree associated with arterial wall state in both age groups. According to the results of multivariate logistic regression analysis a relationship between risk factors and arterial wall parameters is stronger in the younger group as compared with the older one. Conclusion. Systolic blood pressure and fasting hyperglycemia must be the main targets of CVD primary prevention in older age group, while in younger age group other traditional risk factors must be taken into account as well.
253-259 594
Aim. To study pharmacokinetics of apixaban in patients with atrial fibrillation and cardioembolic stroke in acute phase. Material and methods. 17 patients (14 women and 3 men), aged 76.6±9.5 years with atrial fibrillation and cardioembolic stroke in acute phase were enrolled into the study. High performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Results. Intake of a single dose of apixaban 5 mg is described by the following pharmacokinetic parameters: geometric mean of Cmax 124.5 ng/mL (CV%=48), AUC (0, τ) 1008.0 ng•h/mL (CV%=48), AUC (0, ∞) 2751.6 ng•h/mL (CV%=82), median Tmax 3 hours (min 1, max 4), mean t½ 16.9 h (SD 13.6). Negative correlation between NIHSS stroke severity score and Tmax was found (r=-0.628, p=0.007) as well as positive correlation between apixaban t½ and patient age (r=0.638, p=0.01). A tendency to increase in AUC (0, ∞) was observed according to CHA2DS2-VASc points amount but it did not reach the statistical significance (r=0.620, p=0.14). Conclusion. For the first time in Russia pharmacokinetic data of apixaban were obtained in patients with cardioembolic stroke in acute phase. It could be the basis for the development of new personalized approaches to anticoagulation therapy in these patients. Keywords: new oral anticoagulants, apixaban, pharmacokinetics, atrial fibrillation, cardioembolic stroke
260-264 478


Aim. To assess real clinical practice of prescribing beta-blockers (BB) and its compliance with updated guidelines, using data from outpatient registers that are carried out in medical institutions of different levels. Material and methods. We analyzed data from two outpatient registries - RECVASA and PROFILE. RECVASA register included patients aged ≥18 years with arterial hypertension (HT), ischemic heart disease (IHD), chronic heart failure (CHF) and atrial fibrillation (AF) that consulted in 3 outpatient clinics of Ryazan city in 2012-2013 (n=3690). PROFILE register included patients aged ≥18 years with HT, IHD, CHF, AF that consulted in specialized cardiac unit of the State Research Center for Preventive Medicine in 2011-2015 (n=1531). Results. There were differences in the basic characteristics of the registers: in the RECVASA register average age of patients was higher, HT, IHD and CHF were more frequent; PROFILE register included more patients with the history of myocardial infarction. In the RECVASA register 41.5% (n=1533) of patients received BB, and in the PROFILE register – 47.7% (n=731). The most frequently prescribed BB was bisoprolol in all cardiovascular diseases. Conclusion. In a specialized medical institution BB used more often under the conditions where they are necessary. The choice of a specific BB inside the pharmacological group, even in a specialized medical institution does not always correspond to clinical guidelines and evidence-based medicine.

265-271 460

Aim. To study the clinical and laboratory characteristics of patients with stable angina that are sensitive or resistant to acetylsalicylic acid (ASA) before and after coronary artery bypass graft (CABG) surgery. Material and methods. Patients (n=60) with stable angina III-IV functional class, undergoing CABG, were included into the study. In the first postoperative day all patients started to take ASA in enteric form at a dose of 100 mg. To determine the sensitivity to ASA platelet aggregation induced by adenosine diphosphate (ADP 5μM) and arachidonic acid (1 mM) before and after incubation with ASA in vitro was studied one day before CABG and at the 1st and 10th days after CABG using an optical aggregometer. Dielectric properties of blood and its components were also studied with the original Fourier spectrometer. Results. The ASA-resistance rate was 26.7%. The ASA-resistant patients as compared with ASA-sensitive patients more often received selective cyclooxygenase 2 (COX-2) inhibitors (44% vs. 17%, respectively, p<0.05) after CABG. They had higher serum creatinine levels at the 1st day after CABG (153.7±49.9mmol/L vs 115.3±29mmol/L, respectively, p=0.028), >and very high erythrocyte sedimentation rate at 10th day after CABG (80.625±21.3 mm/h vs 54.6±26.5 mm/h; respectively, p=0.028). 33% of patients had resistance to en-teric form of ASA during 10-day therapy after CABG, however, platelet aggregation induced by arachidonic acid was low in in vitro platelet incubation with ASA. This points at decreased bioavailability of enteric forms of ASA. “Transient” ASA-resistance was detected in 12.5% of ASA-resistant patients on the 1st day after CABG due to cardiopulmonary bypass. Significant differences in the dielectric characteristics of blood and platelets were found in the groups of ASA-resistant and ASA-sensitive patients 10 days after CABG. Conclusion. Cardiopulmonary bypass, COX-2 inhibitors, renal dysfunction, the inflammatory response, may be possible reasons of the ASA-resistance after CABG. Changes in dielectric parameters of blood and platelets were found in the ASA-resistant patients.

272-276 418

Aim. To assess the impact of metabolic abnormalities in combination with obstructive sleep apnea on endothelial function and vascular stiffness parameters in patients with arterial hypertension 1-2 degrees. Material and methods. Patients (n=74) with metabolic syndrome and obstructive sleep apnea were included into the study. All patients underwent cardiorespiratory monitoring of sleep using SomnoCheck2 device (Wiennmann, Germany) and were divided into two groups based on its results. Patients with apnea-hypopnea index (AHI) <30 episodes per hour were included into group 1 and patients with AHI >30 episodes per hour – into group 2. Monitoring of ambulatory blood pressure (BP) and arterial stiffness was performed by the device BPLab ("Peter Telegin", Russia). Endothelial function was assessed in a probe of flow-mediated dilation by the ultrasound device MyLab 90 (Esaote, Italy). Diameter of the common carotid artery (DCCA) and the intima-media thickness (IMT) were determined. Results. Patients with AHI >30 episodes per hour had higher mean daily and night systolic BP and pulse BP in aorta and brachial artery. Pulse wave velocity in aorta in per day averaged was also higher in these patients (8.2±0.8 vs 9.1±1.1 m/sec; p<0.05). Mean level of flow-mediated dilation was significantly lower in patients with severe sleep apnea> (8.8% (5.6; 13.1) vs 4.5% (2.2; 8.0); p<0.05). Prevalence of negative index of reactivity in group 2 was 2 times higher than this in group 1. An increase in IMT and DCCA in patients with severe obstructive sleep apnea was also revealed. Conclusion. Severe sleep apnea in patients with metabolic syndrome in combination with hypertension aggravates structural changes and endothelial dysfunction of the main arteries, as well as contributes to the progression of atherosclerosis.

277-284 582

Aim. To study the parameters of diastolic function of the right ventricle (RV) in patients with ischemic heart disease (IHD) in different age groups. Material and methods. Patients (n=678) with IHD aged 38 to 85 years were included into the study. They underwent echocardiography with assessment of RV diastolic function. The following parameters were assessed: rate of early and late diastolic RV filling (Et and At), rate of early and late diastolic motion of the ring of the tricuspid valve (e't and a't), the propagation velocity of RV early filling flow (Vpt). All patients were divided into 2 groups: 1st one - patients up to 60 years old (n=282) and the 2nd group - patients 60 years and older (n=396). Results. In IHD patients RV diastolic dysfunction was detected more often in older age group (34.3%) than in group of patients younger than 60 years (22.3%, p=0.008). The next findings were found in the 2nd group: increase in At; reduction in Et/At ratio and e't/a't, as well as higher levels of systolic and mean pulmonary arterial pressure and the greater the thickness of the RV wall. The following parameters of diastolic RV function correlated with age: At (p=0.004); Et/At (p=0.001); Vpt (p=0.002) and e't/a't ratio (p=0.004). Conclusion. The results should be used in assessment of diastolic RV function in patients of different age groups.

285-290 455

Aim. To estimate probability of atrial fibrillation (AF) recurrence at various methods of sinus rhythm recovery. Material and methods. Patients (n=153) with nonvalvular AF lasting from 24 hours to 6 months were examined. All patients were divided into 3 groups. In group 1 (n=49) sinus rhythm was restored by the drug therapy, in the group 2 (n=57) – by the electrical cardioversion, and in the group 3 (n=47) patients underwent radio-frequency isolation of pulmonary veins. Echocardiography was performed in all patients during AF, and also on the 1, 3, 5, 15 days and in 6 months after sinus rhythm recovery. Results. The absence of AF paroxysms within first 2 weeks after sinus rhythm recovery was a significant predictor of sinus rhythm preservation (р<0.001) and reduction in a number of AF paroxysms р<0.001 during 6 months of follow-up. Emergence of AF paroxysms during the first 2 weeks predicted an increase of their probability within next 6 months (odds ratio=15.37). Significant interrelation between the time of left atrium function restoration (peak A<0.5m/s) and probability of AF paroxysms emergence in early (up to 2 weeks) and late (till 6 months) follow-up periods was also observed (р<0.05). Conclusions. Peak A>0.5 m/s measured by transmitral flow in the first 24 hours after sinus rhythm recovery as well as absence of AF paroxysms within 2 first weeks after sinus rhythm recovery were significant predictors of the sinus rhythm preservation up to 6 months at any type of cardioversion.

291-295 511

Aim. To study the reasons of low adherence to treatment in patients after myocardial infarction as well as methods of its correction considering the mental and emotional state of patients. Material and methods. Patients (n=115) after myocardial infarction registered in "Acute Myocardial Infarction Register» were enrolled into the study. The Moriscos-Green scale was used to determine the degree of adherence to treatment, and psycho-emotional state of patients was assessed by the Hospital Anxiety and Depression Scale (HADS). The special questionnaire was used to study the causes of poor adherence. Results. Only 45% of patients after myocardial infarction have a high commitment to the doctor's recommendations. The main reason for low adherence was forgetfulness (42%). Among other reasons were: fear of side effects (16%); lack of therapeutic effect according to patients' opinion (12%); doubts about the doctor's prescriptions (14%); a large number of prescribed drugs (12%); high cost of drugs (4%). The structure of the causes of poor adherence to treatment varied greatly depending on the psycho-emotional status. Adherence to treatment can be improved by specific physician’s actions (48.5% of patients). At the same time 14% of patients did not want to take drugs for a long time under any circumstances. Conclusion. Adherence to treatment of patients after myocardial infarction deserves attention from doctors. The personalized approach considering patient’s opinion, as well as their specific features, is essential for the development of ways to improve adherence.


296-301 481
Gender differences can significantly affect mortality in ST-segment elevation myocardial infarction (STEMI) in real practice. Aim. To evaluate the effect of gender on mortality in STEMI. Material and methods. Outcomes of in-hospital stage of treatment of 553 men (67.7%) and 263 women (32.3%) were analyzed in single-center retrospective study. Primary percutaneous coronary intervention (pPCI) and pharmacoinvasive strategy (PIS) were used in 160 (60.8%) and 103 (39.2%) women, respectively, as well as in 295 (53.3%) and 258 (46.7%) men, respectively. Patients with time ″primary medical contact (PMC) – balloon″ less than 60 min and ″symptom - PMC″ more than 6 hours were excluded. The majority of patients were in a time interval ″PMC - balloon″ about 120 minutes. Results. Mortality in women was significantly higher than this in men regardless of the reperfusion strategy – 15.3% in whole (18.1% at pPCI and 10.9% at PIS), and 3.1% in whole (5.1% at pPCI and 0.8% at FIS), respectively (p<0.001). The probability of lethal outcome in women was 4 times higher than this in men (odds ratio 4.4; 95% confidence interval 2.7-7.1). Conclusion. Clinical characteristics of the patients due to gender differences make a significant contribution to the course of STEMI. Women more often have severe complications and a worse in-hospital prognosis.


302-305 446
Presented case report demonstrates the efficacy and safety of hospital use of thrombolytic agent Fortelizin in pharmaco-invasive strategy for the treatment of a patient with acute myocardial infarction and with a long history of ischemic heart disease and long-term dynamics of the verified angiographic progression of coronary atherosclerosis. Hospital thrombolytic therapy with Fortelizin was vital alternative in case of a substantial time delay in mechanical reperfusion of the myocardium.


306-313 532

Adverse events (As) of medicines are becoming a more serious problem of health care and society due to the growth of the pharmaceutical market. Incomplete information about AEs of drug therapy is an important aspect of this problem. The use of the register method is very promising in the study of adverse drug reactions in clinical practice. Aim. To study the AEs of drug therapy in the PROFILE outpatient register. Material and methods. Primary patients (n=1531) were included into the PROFILE outpatient register from January 2011 to August 2015. The median age of patients was 63 (54; 71) years. The registration card of patients and patient questionnaires were used within the register for the database creation. Analysis of retrospective data of the register was fulfilled Results. Various AEs were reported in 223 (14.6%) patients. Total anamnestic information on 301 cases of AEs was collected: 223 cases were recorded once, 63 – twice, 15 – three times. Patients with AEs were older than patients without AEs ((p<0.0001). AEs were registered most frequently in the use of ACE inhibitors and acetylsalicylic acid: an average of 15% of all cases, each. Various allergic reactions and symptoms of gastrointestinal disorders (pain, nausea, vomiting, diarrhea, etc.) were leaders in the structure of AEs. Naturally there were more patients without AEs among those, who did not take medications. Among patients treated with 6 to 10 medications per day, there were 1.5 times more people who had at least one AE (p<0.0001). Conclusion. The use of the register method allows to add information about the safety of various drugs. However, analysis of the prospective data of the PROFILE register looks the most promising for the solution of this problem.

314-316 378
The results of the round-table meeting "Registers in cardiology: the basic rules of management, modern experience and the results of their creation in the various regions of the Russian Federation" are presented. Experts from different cities of Russia, who were involved in carrying out the registers of various cardiovascular diseases (CVD) were among participants of the meeting. The importance of modern registers to assess the real state of prevention, diagnosis and treatment in the different institutions providing practical health care is stressed. The need in rapid implementation of register’s conclusions into practice in order to improve health care quality and to increase efficiency of CVD and their complications prevention is indicated.


317-324 515
The heart is related with vascular system anatomically and functionally. Structural and functional changes in the arterial bed increase afterload on the left ventricle (LV), and can change its function, leading to the restructuring of the LV adaptation. Systolic blood pressure (SBP) in the aorta, directly reflecting the load on the LV, differs significantly from the SBP in the brachial artery due to delaying the occurrence of a reflected wave in the aorta. Left ventricular-arterial interaction is a concept that helps to understand the various options for the «optimal» functioning of the cardiovascular system, the effects of changes in the arterial bed to heart function. Methods of analysis of left ventricular-arterial interaction, clinical consequences of the breach and the effects of antihypertensive therapy are presented in the review; the results of the authors own studies are also presented.
325-330 541
According to a recent study, Russian physicians often and sometimes unreasonably find it impossible to use statins in patients with cardiovascular diseases and concomitant chronic liver diseases. Analysis of domestic publications of recent years reveals the following factors which can impede overcoming statinophobia: 1) fragmentary and contradictory statement of the problem "Statins and liver" in Russian clinical guidelines for management of patients with high cardiovascular risk; 2) common perception that isolated transaminase increase in response to statin therapy is an indicator of "cytolysis" or "cytolytic syndrome"; 3) unreasonably overestimated lipid-lowering activity of combination therapy with low doses of statins and ursodeoxycholic acid; 4) view of the inadmissibility of statin use in patients with transaminase levels more than three upper limit of normal. To overcome these shortcomings and mistakes it seems appropriate to issue national clinical guidelines on statin use in high cardiovascular risk patients with underlying liver disease and/or with elevated transaminases.
331-336 496
Atrial fibrillation (AF) is the most common heart rhythm disturbance. It is believed that the primary form of AF is genetically determined in most cases, but the genetic component cannot be excluded in the secondary form of AF. AF is a heterogeneous disease and many authors proved its relationship with other genetic heart disease. In most cases, certain combinations of polymorphisms of different genes promote the development of AF. The study of genes of renin-angiotensin-aldosterone system (RAAS) is especially important, because the role of this system in AF pathogenesis is currently studding most intensively. These studies are of great practical interest, as associative effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in the prevention of AF is revealed. RAAS blockers are able not only to reduce the risk of new-onset AF in hypertensive and normotensive patients but also prevent recurrence of AF. Furthermore, experimental studies showed that RAAS blockers prevent not only the remodeling of the left ventricle, and also the left atrium, pointing to the pathogenesis of AF. So, screening for susceptibility genes and the study of their polymorphism is currently an important focus in the study of AF.
337-343 512
Venous thromboembolism (VTE) is one of the most common cardiovascular disease, and can lead to death or the development of complications and disability. Modern approaches to the determination of the treatment strategy in patients with VTE are considered. The role of thrombolytic therapy is highlighted, as well as the choice of anticoagulants, including new oral anticoagulants (NOAC). EINSTEIN-PE is the only, specially planned and performed study of the NOAC in patients with pulmonary embolism that confirmed the validity of monotherapy tactics with rivaroxaban in patients with VTE. The results of this study are considered in detail.


344-350 493
TGR5 are G-protein-linked, membrane bile acids receptors that widely express in tissues of animals and humans. Namely tissue localization of TGR5 determines biological effects of activation of these receptors. This review focuses on the role of TGR5 as a new pharmacological target for the treatment of patients with metabolic syndrome, diabetes, obesity, atherosclerosis, liver disease and cancer processes.
351-358 455
Effect of hyperlipidemia on morbidity and mortality in elderly patients is considered. Authors also cover issues of efficacy and safety of lipid-lowering therapy in primary and secondary prevention of cardiovascular diseases in patients ≥80 years of age who are the most quickly growing group of population and have the highest cardiovascular risk. They stress the need to take into account polymorbidity and polypharmacy that increase the risk of adverse reactions due to the use of both statins and their drug-drug interactions, which requires an assessment of risk/benefit ratio. In addition, there is a need for development of reliable prognostic tools to predict relevant outcomes (e.g., stroke, decrease in functionality/independence, quality of life reduction) and rationales for lipid-lowering therapy in the elderly and also their adherence to treatment.


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