Rational Pharmacotherapy in Cardiology

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Vol 12, No 4 (2016)
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366-375 712

Aim. To study standardized all-cause mortality and cardiovascular mortality (or deaths due to diseases of the circulatory system) in Irkutsk and Moscow including assessment in gender and age subgroups.

Material and methods. To compare mortality in the two cities data of Federal State Statistics Service were used with calculation of coefficients of mortality adjusted for European age pattern.

Results: Age-standardized indices of mortality per 100,000 of population were significantly lowerin Moscow as compared to Irkutsk in the entire sample (697.6 vs 1157.8; p<0.00001), in men (904.0 vs 1364.3; p<0.00001) and in women (535.1 vs 822.7; p<0.00001), and also in all age subgroups above 25 years. Cardiovascular diseases were dominated in the mortality patterns of the compared cities: 47% in Irkutsk, 64% in Moscow. Chronic forms of ischemic heart disease (47.9% in Irkutsk and 45.9% in Moscow) and cerebrovascular diseases (15.9% in Irkutsk and 16.7% in Moscow) were prevalent. There were significant distinctions in death rates encoded in such headings as: “Otherforms of acute ischemic heart disease”, “Atherosclerotic heart disease”, “Cerebral atherosclerosis”, “Hypertensive encephalopathy”, and “Unspecified cardiomyopathy”.

Conclusion. Irkutsk had higher standardized coefficients of all-cause and cardiovascular mortality as compared to Moscow in the total population, in men and in women and in majority of age subgroups. This can be explained by economic, social and climatic factors.

376-379 871

Aim. To study the rate of prescription of oral anticoagulants (OAC) in patients with atrial fibrillation (AF) depending AF type and the reasons for their not-prescribing according to cohort study data.

Material and methods. Patients (n=58) with AF were included into the study. The rate of OAC, including new OAC (NOAC), prescription depending type AF and the reasons for their not-prescribing were studied.

Results. The rate of OAC use was 46.5% (warfarin – 22.4%, NOAC – 20.7%), antiplatelet agents use – 60.3%. The reasons for the lack of OAC use were: contraindications (high risk of hemorrhage or bleeding history) – 5.2%; patient’s inability to comply with the recommendations and the valvular AF, which does not allow to recommend NOAC – 25.8%; preference for a doctor based on the patient's refusal or preference – 22.4%. OAC use in patients with persistent AF was recorded significantly more frequently than in paroxysmal AF (85.71% vs 24.32%; χ2=17.9; p<0.0001).

Conclusions. A large part of patients with AF remains without OAC prescribing. More active use of NOAC will allow to correct current situation

380-384 763

Aim. To study circadian blood pressure (BP) profile in patients with gout depending on the presence of arterial hypertension (HT) and their relationship to the renal filtration function.

Material and methods. Patients with gout (n=87) were included into the study. All the patients underwent ambulatory BP monitoring (ABPM) with the assessment of circadian BP profile, determination of uric acid serum levels, glomerular filtration rate (GFR) was evaluated by CKD-EPI method. Depending on GFR level, all the patients were divided into 2 groups - with renal dysfunction or without one.

Results. ABPM revealed circadian BP dysregulation in 55% of gout patients both with HT and without HT. Chronic kidney disease (CKD) was revealed in 72.4% of male patients, with the prevalence in patients with HT (76.6 vs 61%; p<0.001). Correlations between uric acid levels and some ABPM indicators and GFR were determined.

Conclusion. Obtained data suggest the contribution of hyperuricemia in disorders of systemic and renal hemodynamics, leading to the early development of CKD.

385-390 761

Aim. To study the prevalence of high residual platelet reactivity (HRPR) during the dual antiplatelet therapy (DAT) with acetylsalicylic acid (ASA) and clopidogrel by optical aggregometry in patients with ischemic heart disease (IHD) after percutaneous transluminal coronary angioplasty (PTCA) in clinical practice, as well as to determine its value for the prediction of clinical course and outcome of disease.

Material and methods. Patients after PTCA and during DAT were included into the study. Evaluation of the functional activity of platelets by optical aggregometry was performed in all patients at baseline. Resistance to ASA, clopidogrel and DAT were detected. Endpoints included cases of repeated atherothrombotic events (sudden cardiac death, myocardial infarction, unstable angina, ischemic stroke, stent thrombosis). Adherence to therapy was evaluated by Morisky-Green test.

Results. 97 patients were included into the final analysis. The risk of myocardial infarction or unstable angina pectoris in the ASA-resistant patients was significantly higher than this in the DAT-sensitive patients [relative risk (RR)=7.68; 95% confidence interval (CI) 2.8-20.54; p=0.045]. Maximum RR for stent thrombosis was in clopidogrel-resistant (RR=7.1; 95% CI 1.41-35.82; p=0.0485) and DAT-resistant patients (RR=12.8; 95% CI 4.5-36.38; p=0.0491), compared with patients with a sensitivity to antiplatelet therapy. DAT-resistance was associated with a higher RR of the combined endpoint, compared with the sensitivity to antiplatelet therapy (RR=10.24; 95% CI 3.96-26.5; p=0.046]), and have a tendency to association with increased risk of combined endpoint compared with isolated ASA-resistance (RR=1.3; 95% CI 0.68-2.6; p=0.081).

Conclusion. HRPR during DAT is common in clinical practice in patients with ischemic heart disease after PTCA. Routine use of optical aggregometry in DAT may help to identify patients with an increased risk of thrombotic events in the postoperative period and to assign them an alternative antiplatelet therapy.

391-395 579

Aim. To study the relationship of arrhythmias, registered by the electrocardiography (ECG) and ECG Holter monitoring, with the changes of the heart and disorders of its function detected by echocardiography in the adult population of the Arctic, living in unfavorable environmental conditions.

Material and methods. Patients (n=348) of both sexes, aged 20 years and older, were randomly selected and examined. All participants were carried out ECG recording in 12 standard leads, Holter monitoring and transthoracic echocardiography.

Results. Statistically significant associations between certain types of arrhythmias and echocardiographic changes were observed. There were revealed correlations of medium strength: between atrial fibrillation (AF), registered by ECG and dilatation of the left (r=0.3215) and right (r=0.3275) atrium; between AF, registered by Holter monitoring, and left ventricular (LV) systolic dysfunction (r=0.3216); between premature ventricular contractions, registered by Holter monitoring, and LV hypertrophy (r=0.3332).

Conclusion. The аassociation between arrhythmias and structural and functional changes of the heart in individuals living in adverse climatic conditions were confirmed.

396-402 587

Aim. To study morphometric changes of the left ventricle (LV) and characteristics of peripheral hemodynamics in patients with drug resistant hypertension (HT).

Material and methods. In total, 120 patients with unmanageable HT of 2-3 degrees, that considered by physicians as drug resistant HT, were included into the study. Patients with HT resistant to full-dose triple antihypertensive therapy (n=43) were included into Group 1. Patients with HT controlled by combination therapy (n=83) were included into Group 2. All the patients underwent echocardiography, volumetric compression oscillometry (to study hemodynamic parameters). Stiffness index (SI, m/s) and reflection index (RI,%) of the pulse wave were also analyzed.

Results. The increase in linear and volumetric LV sizes, severe LV hypertrophy were found in Group 1. LV mass index (LVMI) in patients in Group 1 was 134.0±6,5g/m² vs 98.4±3.3 g/m² in Group 2 (p<0.001). LVMI in men in Group 1 was 150.02±10.7 g/m² vs 99.2±4.5 g/m² in Group 2 (p<0.001). LVMI in women in Group 1 was 126±7.8 g/m vs 102.5±3.4 g/m² in Group 2 (p<0.05). The relative left ventricular wall thickness in Group 1 was 0.60, vs 0.50 in Group 2 (p<0.05). In patients of group 1 compared with group 2 there were also found a reduction in arterial compliance (0.84±0.06 vs 1.0±005, respectively; p<0.05), increased pulse wave velocity (820.14±16 vs 741.11±19 cm/sec, respectively; p<0.05), and increase in specific peripheral vascular resistance.

Conclusion. Most of patients with drug resistant HT have concentric LV hypertrophy and concentric LV remodeling. The microvasculature remodeling takes place much earlier and is accompanied by possible rarefaction. Increased vascular stiffness is more pronounced in patients with drug resistant HT. It was confirmed by decrease in arterial compliance, and increase in outer diameter of the artery, that led to increase in pulse wave velocity


403-413 848

The summarizing of the experience of medical care at the cessation of tobacco use and the treatment of tobacco addiction and consequences of tobacco consumption in the Russian Federation (RF) as well as suggestions for their improvement are presented.

For the effective implementation of health care, aimed at the cessation of tobacco use, treatment of tobacco addiction and consequences of tobacco consumption in the RF it is necessary to solve the following problems:to include doctors of all specialties in the process of medical care and treatment oftobacco addiction and consequences oftobacco consumption in the RF; to ensure effective implementation of the existing legal documents determining the procedure for providing medical aid, aimed at ending the use of tobacco, treatment of tobacco dependence and consequences of tobacco consumption, greater control over their performance and quality of their implementation; to expand of the network of medical offices for cessation of tobacco consumption on the basis of existing structures in primary health care settings (including women's and children’s outpatient clinics), as well as hospitals and health resorts, their provision of personnel and equipment, introduction of group forms of work; to ensure a permanent system of training on assistance at the cessation of tobacco consumption, the treatment of tobacco dependence and consequences of tobacco consumption, including the introduction of medical assistance cycle on cessation of tobacco consumption for student training in medical schools and programs for postgraduate education of health professionals


414-423 804
Serelaxin (recombinant molecule of the human relaxin-2) is an innovative drug for the treatment of acute heart failure. Preclinical and clinical studies demonstrated the ability of serelaxin to relieve the symptoms of heart failure, provide a significant reduction in congestion and have a protective effect on the heart, kidneys, liver. 48-hour serelaxin infusion in patient with ischemic cardiomyopathy and severe decompensated heart failure with cardio-hepatic syndrome led to significant regression of systemic congestion (evaluated by physical signs and by bioimpedance vector analysis), the improvement of structural and functional state of the myocardium (evaluated by standard echocardiography and global systolic longitudinal deformation of the left ventricle with speckle tracking echocardiography), regression of cardio-hepatic syndrome, improvement of renal function. Serelaxin therapy was well tolerated and was safe. Presented case report demonstrates beneficial effects of serelaxin on the heart failure symptoms and the organoprotective effects.


424-429 1148
The problem of non-alcoholic fatty liver disease (NAFLD), which is an independent risk factor for a number of cardiovascular diseases (CVD), is considered. The high prevalence of cardiovascular risk factors is demonstrated in patients with NAFLD in Russian population. Common pathophysiological mechanisms of NAFLD and CVD (insulin resistance and excessive accumulation of lipids in the liver) are discussed. The "new" risk factors (thickening of the pericardial fat, endothelial dysfunction, thickening of the intima-media complex, increase in plasma level of C-reactive protein and others.) are found in patients with NAFLD, along with a greater prevalence of traditional factors of CVD risk (obesity, diabetes, metabolic syndrome and etc.). The relationship of NAFLD with atherosclerosis, dyslipidemia, features of bile acids metabolism in NAFLD and ability to influence these components are also considered.


430-434 779

Aim. To assess the influence of patients’ adherence to attendance at outpatient clinics (OPC) on direct outcome of acute coronary syndrome (ACS).

Material and methods. Patients (n=320) hospitalized with ACS were divided into 3 groups depending on their attendance at OPC before ACS: group A - committed to attending OPC (n=139); group B - partially committed to attending OPC (n=103); group C - non-committed to attending OPC (n=78). Direct outcome of ACS and its connection to attendance at OPC was analyzed. The primary end point of the study was the development of myocardial infarction or unstable angina as direct outcome of ACS.

Results. The majority of patients had myocardial infarction as direct outcome ofACS.Development of myocardial infarctionwas aboutthe same in3groups of attendance at OPC (p=0.158). Influence of patients’ adherence to attendance at OPC on direct outcome of ACS was not found (RR=0.602, р=0.123). History of ischemic heart disease and myocardial infarction didn’t change this predicted pattern. In the absence of significant influence of patients' adherence to attendance at OPC on the direct ACS outcome, it was decided to evaluate the effect of pre-hospital care quality on direct outcome of ACS, regardless of patients’ adherence to attendance at OPC. Quality of pre-hospital therapy was low, but therapy of patients with unstable angina as an outcome of ACS was significantly better than therapy of patients with myocardial infarction as an outcome of ACS. Taking antiplatelet agents, beta-blockers and long-acting nitrates before ACS development significantly reduced the risk of myocardial infarction as an outcome of the ACS.

Conclusion. Patients’ adherence to attendance at OPC didn’t influence direct outcome of ACS by itself, even considering the history of ischemic heart disease and myocardial infarction. Quality of pre-hospital therapy of patients with unstable angina as an outcome of ACS was significantly better than therapy of patients with myocardial infarction as an outcome of ACS. This is especially true in terms of drugs with proven effects on disease outcome. Taking antiplatelet agents, beta-blockers and long-acting nitrates before ACS development significantly reduces the risk of myocardial infarction as an outcome of the ACS


435-442 928

Influence of left bundle branch block (LBBB) on left ventricle (LV) diastolic function and mechanisms of LV torsion remains underestimated.

Aim. To study the relationship of LV diastolic function and LV torsion in patients with cardiomyopathy and LBBB in comparison with patients with cardiomyopathy and normal intraventricular conduction.

Material and methods. Patients with cardiomyopathy (n=74) and LV ejection fraction <40% were included into the study and divided in two groups with narrow QRS complex and LBBB (the mean QRS duration = 153 ms). Echocardiography was performed in all patients with hemodynamic indices detection, and myocardium strain and torsion estimation.

Results. The patients with LBBB showed less twisting, than patients without LBBB (3.24±3.35° and 5.87±3.83°, respectively, p=0.013914), but significant diastolic function differences between groups were absent. Despite the lack of difference in heart remodeling indices, subgroup of patients with LV rigid body rotation showed significantly less LV twisting and changes in pulmonary vein flow related to LV high end diastolic pressure. In the rigid body rotation group systolic left atrial filling fraction was 32.3±8.07%, whereas in the group with a physiological counter-rotation - 53.1±10.1% (p=0.000226). Potential reason of these findings was interventricular dyssynchrony. Deviation of time interval to peak myocardial systolic velocity between opposite basal segments in group with LBBB and anomalous LV rotation was more (63.3±35.1 ms) than this in group with LBBB and physiological LV rotation (8.0±17.9 mc, p=0.015922). This finding suggests that LV rigid body rotation in patients with LBBB may reflect a more pronounced mechanical dyssynchrony.

Conclusion. LBBB has complex negative influence on process of LV electric activation and contraction which results in deterioration of LV twisting, mechanical dyssynchrony and deterioration of diastolic function. In disorders of intraventricular conduction and local contractility, assessment of pulmonary vein flow, possibly, more precisely reflects diastolic function status.


443-449 889
In XANTUS study the safety and efficacy of factor Xa inhibitor rivaroxaban were evaluated in routine clinical practice in patients with non-valvular atrial fibrillation. In consecutive patients who started treatment with rivaroxaban, all adverse events were recorded every 3 months for 1 year. Conclusions of major bleeding, symptomatic thromboembolic complications (stroke, systemic embolism, transient ischemic attack, and myocardial infarction) and death from all causes were centrally adjudicated. In total 6784 patients were treated with rivaroxaban at 311 centers in Europe, Israel, and Canada, on average, 329 days. The mean CHADS2 and CHA2DS2-VASc scores were 2.0 and 3.4, respectively. Treatmentemergent major bleeding occurred in 128 patients (2.1 events per 100 patient-years), 118 (1.9 events per 100 patient-years) died, and 43 (0.7 events per 100 patient-years) suffered a stroke. XANTUS is the first international, prospective, observational study to describe the use of rivaroxaban in a broad non-valvular atrial fibrillation patient population. Rates of stroke and major bleeding were low in patients receiving rivaroxaban in routine clinical practice.
450-458 803
Data of the World Health Organization and numerous clinical studies have shown a steady increase in the prevalence of obesity in the world. The number of obese people has doubled in the last three decades. The increase in obesity prevalence with age was found in Russia in the large epidemiological study ESSE-RF. Besides, increase in obesity prevalence was observed among men. Special attention is necessary for patients with overweight or obesity in the primary prevention of chronic non-communicable diseases, such as cardiovascular disease and type 2 diabetes. Therapy aimed at addressing the risk factors of adverse outcomes is rational, if the patient has a disease associated with obesity.
459-464 1057
Despite the possibilities of contemporary pharmacotherapy, more than 80% of hypertensive patients do not achieve target blood pressure levels. Besides the obvious reasons – poor adherence of patients to treatment and non-rational therapy, there are other objective risk factors of resistance. Three main modifiable causes of resistant hypertension, that are often underestimated, are considered: obesity, obstructive sleep apnea syndrome and primary hyperaldosteronism. Understanding these mechanisms of resistance and their diagnostic criteria can improve the results of resistant hypertension treatment.
465-470 692
Atrial fibrillation (AF) – is the most common tachyarrhythmia, which is diagnosed in 1-2% of the population. Non-valvular AF increases the risk of ischemic stroke in 5-7 times. More than 50% of thromboembolism originating from the heart is associated with non-valvular AF. Therefore, prevention of ischemic stroke and systemic embolism is one of the main aims of AF treatment. For a long time for prevention of them oral anticoagulants were used mainly from the group of vitamin K antagonists, most often warfarin. In connection with the known disadvantages of warfarin use, the elaboration of new oral anticoagulants (NOAC) became very important in clinical practice. The article presents a contemporary view of the advantages of the NOAC, indications and contraindications for their use. The international recommendations on their use in different clinical situations are analyzed. At the same time, the article deals with some questionable matters of antithrombotic therapy with NOAC at AF and authors give their point of view on a number of studies in the field of clinical arrhythmology. Currently, according to the authors, it is appropriate to speak of a differentiated approach to the appointment of the NOAC, that depends on a whole range of clinical factors, and the results of laboratory and instrumental investigations, rather than to compare these anticoagulants on the principle of "better or worse", as these estimates are not correct, and sometimes they are clearly far from the principles of medical ethics.


471-478 2761
Use of class I antiarrhythmic drugs in the elderly is limited by their adverse drug reactions (ADRs), proarrhythmic effect (I A и I C) and high risk of drug interactions. Disopyramide use should be avoided due to its strong anticholinergic properties associated with the risk of cognitive and physical disorders and falls in the “very elderly” patients. Available data suggest that elderly patients do not have significant limitations for beta-blockers use. However to determine beta-blockers with the best benefit/risk ratio in elderly patients with co-morbidity further clinical trials are needed.



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ISSN 1819-6446 (Print)
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