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Rational Pharmacotherapy in Cardiology

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Vol 13, No 5 (2017)
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https://doi.org/10.20996/1819-6446-2017-13-5

ORIGINAL STUDIES

578-589 252
Abstract

Background. The seasonal variability of blood pressure (BP) and cardiovascular morbidity and mortality motivates researchers to search  for the new approaches of the antihypertensive treatment (AHT) efficacy assessment, including the analysis of interrelation between clinic and ambulatory BP, i.e. BP phenotypes.

Aim. To evaluate the prevalence of BP phenotypes in treated hypertensive outpatients both in winter and summer.

Material and methods. Hypertensive patients under regular AHT with available data of clinic BP and 24-hour BP monitoring both in winter and summer seasons (n=477) were selected from a outpatient database with clinic BP <160/100 mm Hg (n=1762). The BP threshold values from current guidelines were used for the BP phenotypes definition. The “controlled hypertension” phenotype was detected when  clinic and ambulatory BP levels were less than  threshold values, the “uncontrolled hypertension” – when  both levels exceeded the thresholds, the “white coat hypertension (WCH) in treated patients” – when  clinic BP was only increased, the “masked  uncontrolled hypertension” phenotype was ascertained if ambulatory BP was only elevated.

Results. The study included 232 patients examined in Ivanovo (a relatively cold region; mean  age 53.5±9.3 years; 28% men; clinic BP 121.7±7.9 mm Hg; mean  duration of hypertension 4.6±6.3 years) and 245 patients from Saratov (a relatively hot region; mean  age 58.3±10.6 years; 56.3% men; clinic BP 127.5±14.9 mmHg; mean duration of hypertension 9.2±9.2 years; р<0.0001). In the Ivanovo cohort, ratio of BP phenotypes in summer and winter did not differ; the “masked  uncontrolled hypertension” phenotype prevailed (62.1% and 63.8% in winter and summer, respectively); AHT was effective in 27.6% and 29.7% of the patients in winter and summer, respectively. The prevalence of other phenotypes was low: uncontrolled hypertension – 9.5% in winter and 6.0% in summer; WCH in treated patients – less than  1%  in both seasons. The prevalence of BP phenotypes in the patients examined in Saratov differed in winter and summer (χ2=18.127, р<0.0001); the “masked  uncontrolled hypertension” phenotype rate was higher in summer than in winter (50.2% and 32.2%, respectively); the rates of other phenotypes were higher in winter: uncontrolled hypertension – 38.8% and 27.8%, controlled hypertension – 25.3% and 20.8%, WCH – 3.7% and 1.2% in winter and summer, respectively.

Conclusion. We have found no seasonal changes in BP phenotypes prevalence in relatively younger hypertensive patients in a relatively cold region. The “masked  uncontrolled hypertension” phenotype was predominant (>60%) in this region. In contrast, the cohort  of relatively older patients with longer hypertension history examined in a relatively warmer region revealed significantly higher rate of masked uncontrolled hypertension in summer (50.2%) while prevalence of all other phenotypes – in winter.

590-596 266
Abstract

Aim. To study the effect of replacing clopidogrel with ticagrelor on endpoints of hospital period and one year after ST Segment Elevation Myocardial Infarction (STEMI).

Material and methods. The study enrolled 80 patients with STEMI. At the stage  of emergency medical service, all patients received loading doses of acetylsalicylic acid (250 mg) and clopidogrel (600 mg). After 12-24 hours,  the patients were randomized into two groups. Patients of the first group received maintenance doses of acetylsalicylic acid (100 mg/day) and clopidogrel 75 mg/day. Patients of the second  group received maintenance doses of acetylsalicylic acid (100 mg/day) and ticagrelor 90 mg twice a day. ADP-induced platelet aggregation (1.25 and 2.5 mg/ml) and proinflammatory factors blood levels (C-reactive protein [CRP], interleukin 6 [IL-6]) were investigated before clopidogrel replacement, as well as 2 hours and 7 days after its replacement. Endpoints were recorded at the patient's discharge and one year later.

Results. After a year in the ticagrelor group there was a trend towards fewer endpoints compared to clopidogrel group (combined endpoint 14.2% vs

25%, p=0.14). In the ticagrelor group, there was no significant increase in the incidence of bleeding compared with the clopidogrel group both in the hospital period and during the year after the STEMI (large bleeding – 0 vs 3.3%, small bleeding – 25.4% vs 26.6%, p=0.48). On the 8th day of STEMI (7 days after clopidogrel replacement), platelet aggregation in the clopidogrel group was significantly higher compared to platelet aggregation in the ticagrelor group (p=0.00). The level of CRP and IL-6 on the 8th day of hospitalization in the clopidogrel group was significantly higher in comparison with the ticagrelor group (p=0.04 and p=0.01, respectively).

Conclusion. When clopidogrel is replaced with ticagrelor on the 1st day of STEMI, there is a tendency to a lower incidence of endpoints during the first year of follow-up. Such switching is safe from the point of view of hemorrhagic complications and is associated with lower platelet aggregation and inflammation activity estimated 7 days after clopidogrel replacement (on the 8th day of STEMI).

597-601 225
Abstract

Background. The discovery of new genetic predictors of cardiovascular diseases can be used in predicting and diagnosing latent forms of the disease. Wolff-Parkinson-White syndrome (WPW) occurs in all age groups  and detected in 1-30 people per 10000, it manifests mainly in young age (on average 20 years), and the risk of sudden cardiac death is higher than in general population.

Aim. To study the relationship of WPW syndrome with the polymorphism of endothelial nitric synthase gene (NOS3), and to identify genetic predictors of this syndrome.

Material and methods. The study included 51 people with ECG proven WPW syndrome and 153 people with no cardiovascular disease. The patients were divided into subgroups according to sex: 21 women, 30 men. All patients underwent a standard cardiac examination (anamnesis, electrocardiography, echocardiography, bicycle ergometry, transesophageal electrical stimulation of the atria, Holter monitoring) and blood was taken for molecular genetic testing of DNA.

Results. The results showed a statistically significant prevalence of rare genotype 4b\4b NOS3 gene in the control group of women (16.3%; р<0.05) compared with women from the main group, who did not have this genotype, while there was significant prevalence of genotype 4a\4a in the main group of women (81.0%; р<0.05) compared with women from the control group.  In men this prevalence was not found.

Conclusion. The presence of genotype 4b\4b NOS3 gene reduces the likelihood of WPW syndrome and its symptoms in females. In men,  this prevalence is not found, presumably, in connection with some mechanisms of hormonal regulation. The results can be used in the genetic prediction of the course of the disease.

602-608 192
Abstract

The search for effective ways to improve adherence to medication in patients with hypertension at high risk is critical in reducing morbidity and mortality from cardiovascular diseases.

Aim. To assess the possibility of improving adherence to therapy in high-risk hypertensive patients with dyslipidemia by means of electronic version of the SCORE scale in primary care.

Material and methods. 300 hypertensive patients with dyslipidemia aged 40 to 65 years without clinical manifestations of atherosclerosis visiting primary care doctor  (departmental clinic of Moscow) were examined. The study included only patients (n=150) with high cardiovascular risk and target organ damages (microalbuminuria, left ventricular hypertrophy, subclinical carotid atherosclerosis). The patients were randomized into two groups – main (n=76) and control (n=74). All patients were prescribed antihypertensive and lipid-lowering therapy, recommendations for a healthy lifestyle. In the main group, the positive dynamics of risk was demonstrated with the electronic version of the SCORE scale in the case of achieving target levels of blood pressure (BP) and total cholesterol, smoking cessation and weight loss. No such demonstration was done in the reference group.  The duration of study was 12 months. In the groups, evaluation of the achievements of target BP values and lipid variables, risk factors correction, dynamics of SCORE risk and adherence to therapy was done.  Adherence to treatment was assessed by Morisky-Green scale.

Results. By the end of the study, the average Morisky-Green score in the main group was 2.14 vs 1.27 in the control group (p<0.001). In the main group, adherence to antihypertensive therapy persisted for 8.8 months, to statin therapy – 6.74 months; the same characteristics in the control group were 5.73 and 3.6 months, respectively (p<0.001). Achievement of target levels of BP and total cholesterol in the main group  amounted to 55.3% and 35.5% of patients, respectively, in the control group  – 18.9% and 10.8%, respectively (p<0.001). The SCORE risk value was significantly lower in the main group than this in control group (4.09 vs 5.25, respectively).

Conclusion. Demonstration of electronic version of SCORE scale for high-risk hypertensive patients with dyslipidemia allows increasing the patient's adherence to treatment. This leads to the increase in the effectiveness of therapy, better control of BP and lipid parameters, correction of other modifiable risk factors and as a result to reducing overall cardiovascular risk.

609-614 208
Abstract

Aim. To study the clinical effectiveness of patient-oriented therapy in polymorbid patients with arterial hypertension (HT) in comparison with the conventional therapy by the assessment of rationality (secondary combined endpoint) and total mortality (primary endpoints).

Material and methods. Dynamics of rationality and total mortality were evaluated in a circular prospective study in 1000 polymorbid patients with HT under patient-oriented or conventional therapies.

Results. The strategy of patient-oriented therapy demonstrated a statistically significant advantage over conventional therapy by the criterion of the secondary  combined endpoint, starting from 24 week (Student's t-test: p=0.049 at the 50th and 100th weeks; p=0.002 at the 150th week; p=0.004 at the 200th week). By the end of the study in the patient-oriented group, a positive trend in rationality indicators was achieved in the absolute majority of respondents, while in the conventional therapy group the majority of the baseline parameters changed insignificantly.

The total mortality rate in the group of conventional therapy showed a trend of outstripping growth compared with the patient-oriented therapy group, starting from the 50th week of the study. This growth trend was maintained until the end of the study and was of an exponential nature.

Differences in total mortality in the samples were statistically significant. A strong correlation was found between the increase in "rationality" indices and the decrease in total mortality.

Conclusion. The approach based on management of treatment by criterion of rationality, demonstrated an opportunity of increase in efficiency of treatment, including a reduction in total mortality without the involvement of additional resources and medical interventions.

615-621 196
Abstract

Aim. To study the combination and contribution of risk factors (age, hypertension (HT), obesity, diabetes mellitus, chronic kidney disease (CKD), length of illness) leading to the formation of chronic heart failure (CHF) with preserved ejection fraction (EF).

Material and methods. The study included 100 hypertensive patients (aged 40 to 80 years) with concomitant obesity or diabetes or CKD. Patients were divided into 4 groups depending on the presence of one major and/or several concomitant diseases. Echocardiography, assessment of large arterial vessels stiffness indices (SI m/s, CAVI m/s), and determination of small muscle arteries tonus (RI%) were performed in all patients.

Results. Remodeling of the left ventricle (LV) and left atrial (LA) was observed in all patients with comorbid status, as well as reduction in diastolic function. The LV myocardial mass index in the first group was 117.2±31.4 g/m2, in the second one – 125.9±27.4 g/m2, in the third group – 121.5±15.6 g/m2 and in the fourth one – 126.1±11.5 g/m2. A significant increase in the LA volume index was founded in the first group  – 33.4±3.9 ml/m2, in the second one – 39.6±9.1 ml/m2, in the third group – 38.1±5.2 ml/m2 and in the fourth one – 39.8±6.6 ml/m2 (р<0.05). The parameters reflecting the rigidity of large arterial vessels (SI m/s, CAVI m/s) also exceeded the threshold values in each group; significant differences SI were between the first and fourth, second  and fourth groups  (р<0.05), CAVI between the first and third groups  (р<0.05). A significant correlation was found between CAVI and age (r=0.63), which indicated an increase in arterial stiffness with age.

Conclusions. In the formation of CHF with preserved EF, additional factors enhance the changes associated with LV remodeling and LA overload. These changes occur with a progressive decrease in LV diastolic function and increase in myocardial stiffness. HT and obesity are the main contributors to the development of CHF with preserved EF. Remodeling of the LV, LA and vascular system in CHF with preserved EF develop simultaneously.

622-629 702
Abstract

Background. The problem of comorbidity in ischemic heart disease (IHD) has always been given increased attention, due to the high social significance of cardiovascular diseases. However, often the problem solution involved studying cardiac pathology along with concomitant diseases, such as diabetes mellitus, pulmonary or kidneys pathology, etc., but not a comprehensive approach, which takes into account all available comorbidities. An important issue that should be considered in the shift to the personalized medicine is the presence of gender differences, which varies greatly and depends on different correlations with specific comorbidities.

Aim. To study gender differences in comorbidities in patients with IHD.

Material and methods. 742 patients with IHD examined in the Research Institute for Complex Issues of Cardiovascular Diseases in 2011 before elective coronary by-pass surgery were included into the study. All the patients were divided into 2 groups depending on the gender: Group 1 – 147 females, Group 2 – 595 males.

Results. The obtained results reported that women were commonly older than men and more often had excess body weight (p<0.001). The majority of current smokers were males (p<0.001). During preoperative preparation, the development of myocardial infarction (MI) was observed in 12.9% of women and 7.4% of men (p=0.031), while the history of MI was more often found in male patients (p=0.004). The evaluation of the severity of angina pectoris and chronic heart failure (CHF) revealed that in men the I and II functional classes (FC) of angina (p=0.057 and p=0.007, respectively) and stage I CHF (p<0.001) were prevailed, whereas women had angina FC 3-4 (p=0.005 and p=0.050, respectively) and stage IIa CHF (p<0.001). Women more often than men suffered from hypertension (p=0.01) and atrial fibrillation (p=0.024), while peripheral artery disease prevailed among men (p=0.022). The analysis of comorbidities showed that disorders of carbohydrate metabolism, thyroid disease, bronchial asthma and varicose disease were more common in female patients (p<0.05), whereas chronic hepatitis (p=0.079) and urolithiasis – in males (p=0.028). The comorbidity score did not differ significantly between the study groups  (p>0.05), wherein the average level of comorbidity score prevailed among men (70.4%) and women (66%).

Conclusion. Detection of comorbidities in IHD patients based  on gender differences is advisable to improve both  the  immediate results of surgical management and further preventive measures.

NOTES FROM PRACTICE

630-636 247
Abstract

Spasm of the coronary arteries is a dynamic narrowing of one or more coronary arteries, leading to significant restriction of the lumen. The leading role in coronary  artery spasm diagnostic belongs to coronary  angiography and its accompanying provocative tests. Mechanisms of coronary  artery spasm development remain incompletely clarified and it's considered as a multifactorial disease with its own specific risk factors.  Though pathophysiology is no longer a matter of dispute, further  efforts should be aimed at the practical application of the recommendations. Diagnosis of the coronary  artery spasm  has important practical significance, due to the prevailing benefit of calcium antagonists in the treatment and absence of benefit from percutaneous coronary  interventions in most cases. A clinical case of the patient with multivessel, multifocal coronary  artery spasm is presented.

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

637-644 326
Abstract

Aim. To analyze the results of measurements of the blood lipid spectrum of urban  residents of the European part of the Russian Federation.

Material and methods. The results of single assessment of lipid profiles in 22,436 males and 35,100 females at the age from 13 to 94 years in 347 cities and towns  of the European part of the Russian Federation were analyzed. Lipid assays were performed by the Laboratory Service «HELIX» from 28 Jan 2015 to 19 Mar 2016.

Statistical methods included descriptive statistics, the analysis of distributions of sample comparisons and the search of dependencies.

Results. Results of 56,235 measurements of total cholesterol (TC), 22,641 – triglycerides (TG), 21,032 – high density lipoproteins cholesterol (HDL-C) and 22,441 – low density lipoprotein cholesterol (LDL-C) were analyzed. TC above 5.2 mmol/l was identified in 55.78% samples; the proportion of people with LDL-C level above 3.0 mmol/l was 62.95%. The level of TC was the highest at the age of 43 to 62 years in both men and women, while the peak in the increase in TC in men was approximately 10 years earlier, than  in women. In patients of older age groups, TC levels decreased and reached minimum values in men and women of senile age and long-livers. Low level of HDL-C was observed in 24.46% of the total number of samples in men and in 17.68% – in women. The monotonous increase in the average levels of HDL-C was revealed in men with aging. In women the HDL-C levels increased sharply from a minimum at the age of 13 years to a maximum at the age of 25 years with a slight monotonous decrease in the following age periods. However, even in the age older than 83 years levels of HDL-C remained high (1.49 mmol/l in average). The level of TG showed significant inter-age fluctuations, especially in men. The levels of TG above 1.7 mmol/l were recorded in 30.07% of all cases.

Conclusion. Two-factor analysis of variance for all lipid parameters revealed a high statistical significance of gender and age.

ASSOCIATED PROBLEMS OF CARDIOLOGY

645-650 296
Abstract

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, which is frequently present in patients with atherosclerosis or its complications (myocardial infarction, stroke). Subsequently it was revealed that NAFLD may increase cardiovascular risk independently of traditional cardiovascular risk factors. Possible mechanisms of NAFLD-induced increasing cardiovascular risk are increased oxidative stress, subclinical inflammation, insulin resistance, endothelial dysfunction and deranged аdipocytokines profile. Such risk factors as arterial hypertension, dyslipidemia, obesity, diabetes mellitus type 2 often coexist with NAFLD and contribute to increased cardiovascular risk in these patients. Thus, NAFLD can be considered as an additional risk factor of cardiovascular diseases. In this article we discuss in detail the NAFLD-induced mechanisms which increase the cardiovascular risk regardless of traditional risk factors.

651-660 318
Abstract

Problems of iron deficiency and anemia in chronic heart failure (CHF) are discussed in the article. A review of the literature on the epidemiology, etiology and pathogenesis of anemia in this category of patients is presented. Various published data on the effect of anemia on the prognosis of CHF are given. The role of iron deficiency in the development of anemia, the features of its diagnosis and influence on the course of CHF are discussed. The author explains the role of various iron deficiency syndromes in the development of anemia in CHF, suggests a significant predominance of mixed forms of iron deficiency, such as iron deficiency anemia in combination with anemia of chronic disease, which are associated not so much with absolute iron deficiency as with systemic inflammatory response. All the existing approaches to the treatment of iron deficiency and anemia in patients with CHF are presented. The positive and negative results of the use of classical oral iron preparations, intravenous forms,  isolated and combined use of recombinant human erythropoietin are presented. The author discusses the reasons for the failure in the treatment of anemia and the absence of a pronounced effect on the clinical manifestations of CHF in the application of standard approaches in treatment. As a possibility of more effective correction of iron deficiency and anemia in patients with CHF, new preparations of liposomial (sucrosomial) iron for oral administration are offered. The last extremely encouraging clinical results of the use of a new iron formulation in the treatment of iron deficiency and anemia in this group of patients are given.

661-666 443
Abstract

Aim. To study effect of 24-week treatment with lisinopril on blood pressure (BP) and arterial stiffness in patients with arterial hypertension (HT) and rheumatoid arthritis (RA).

Material and methods. Twenty patients with essential HT grade  1-2 and RA (mean age 60.2±7.9 years) were treated with lisinoprilin 24 weeks in open controlled study. Office blood pressure (BP) was 147.2±9.4/87.5±8.6 mm Hg; 24-h mean  BP – 141.8±9.3/82.2±9.6 mm Hg; HT duration was 14.5±9.4 years, and RA duration – 12.3±2.6 years. A high incidence of traditional cardiovascular risk factors was identified: 95% of patients had dyslipidaemia, 45% – obesity, 35% – impaired glucose tolerance. Atherosclerosis of carotid arteries with stenosis less than 25% was diagnosed in 65% of patients. Most patients had a positive rheumatoid factor and cyclic citrullinated peptide antibodies, as well as moderate RA activity and III-IV radiologic stage of RA. All patients received methotrexate as the basic anti-inflammatory drug, 12 (60%) patients – selective cyclooxygenase-2 inhibitors, 6 (30%) patients took corticosteroids equivalent to prednisolone 7.5±5.5 mg per day. Mean  dose  of lisinopril was 12.2±9.8 mg/day. Office BP measurements, 24-hour ambulatory BP monitoring (ABPM), and  arterial stiffness evaluation were  performed initially and  at the end of the study. Arterial stiffness was assessed by cardio-ankle vascular index on the right (R-CAVI) and on the left (L-CAVI).

Results. After 24-week therapy with lisinopril office systolic and diastolic BP significantly decreased by 16.0±7.2/11.6±9.1 mm Hg (p<0.0001) and 11.6±9.1 mm Hg (p<0.0001), respectively. The target BP was achieved in 16 (83%) patients. According to the ABPM 24-week therapy with lisino pril led to a significant (p<0.002) decrease in BP for all referable periods: by 12.4±9.1/7.6±3.9 mm Hg within 24 hours;  by 13.4±10.1/8.0±6.1 mm Hg for daytime; by 10.1±9.3/7.3±6.3 mm Hg for night-time. After lisinopril treatment, R-CAVI decreased from 8.9±1.7 to 8.4±1.6 relative units (p=0.011), L-CAVI decreased from 8.9±1.6 to 8.4±1.5 relative units (p=0.003).

Conclusion. In patients with combination of HT and RA, 24-week therapy with lisinopril had a significant antihypertensive effect and improved the elastic properties of the vessels.

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

667-674 351
Abstract

The off-label prescribing is multifaceted problem and affects  the interests and scope  of activities of different parties. Possible reasons, types of offlabel use of drugs are given in the article, as well as legal regulation of this issue in the Russian Federation and abroad. Such type of prescriptions is broad in various fields of medicine, especially in pediatrics, oncology, obstetrics and gynecology. Often this is due to the inability to perform appropriate randomized clinical studies, because of regulatory difficulties, economic inexpediency and ethical considerations. An additional complication in regulating this process is the fact that in the Russian Federation there is no clear legal basis for the off-label use of drugs,  as well as the fact that clinical recommendations do not have a legal status. It seems relevant to study the assessment of the consequences of off-label drugs use, especially long-term effects. For this purpose, it seems important to use existing medical registers, as well as to create new prospective registers devoted to the study of the consequences of off-label prescribing.

INNOVATIVE CARDIOLOGY

675-683 558
Abstract

Assessment of the left atrial (LA) function is important aspect of comprehensive cardiovascular system estimation. Many cardiac diseases make an impact to LA work either by direct affect on myocardium or hemodynamic condition changing. It is considered, LA and left ventricle diastolic pressure is interrelated, thus without mitral valve disease LA expanding is a sign of LV filling pressure augmentation. Examination of LA size and function by analysis of atrial reservoir, conduit, and booster pump can predict cardiovascular outcomes in patients with cardiomyopathy, ischemic heart disease and valvular heart disease. The last two decades gave new technologies to accurate and comprehensive LA mechanics estimation, in the first place related to tissue Doppler imaging. Atrial strain and strain rate obtained using two-dimensional speckle-tracking echocardiography have proved to be feasible and reproducible techniques to evaluate LA mechanics.

In physiological settings, LA is a highly expandable chamber with relatively low pressures. However in the presence of acute and chronic injury, LA wall stretches. LA stretching is a hallmark of structure changing with myocardial fibrosis and has influence on LA strain and strain rate. LA strain estimation could be useful in the prediction of sinus rhythm restoration and maintenance after cardioversion and catheter ablation. Low values of global longitudinal LA strain indicate irreversible LA remodeling and are related to the atrial fibrillation progression from paroxysmal to permanent forms. The most interesting in these circumstances is the potential contribution of echocardiography to thromboembolic risk stratification in atrial fibrillation and invasive procedures such as atrial ablation. Therefore, at present, the main task is to understand the ways of clinical application of data  obtained during the LA study.

POINT OF VIEW

684-692 335
Abstract

Atrial fibrillation (AF) increases the risk of stroke,  therefore long-term anticoagulant therapy is the standard for the treatment of the absolute majority of patients with this arrhythmia. Variants of anticoagulant therapy include vitamin K antagonists, such as warfarin, whose  benefits are long established, but have a number of disadvantages, as well as their alternative – non-vitamin K antagonists – oral anticoagulants, recommended for the treatment of patients with AF with moderate or high risk of stroke. Adherence to pharmacotherapy is important for the long-term effectiveness of any medication; however, in the "real world" in patients with AF relatively low levels of adherence to drugs compared with clinical studies are expected. Experience in several areas of therapy, including the treatment of cardiovascular disease, shows that a low adherence to a constant intake of medications is common. However,  in this respect, simple dosing regimens may be beneficial, since long-term outcomes in AF are likely to depend on adherence to treatment. Rivaroxaban can be given in fixed doses without routine coagulation control, and phase III studies and actual clinical practice have demonstrated its safety and efficacy in patients with AF, including the elderly and patients with concomitant diseases. Taking an oral anticoagulant, not vitamin K antagonists, in particular rivaroxaban, once a day is potentially capable of improving adherence to therapy and the results of stroke prevention in patients with AF.

693-698 203
Abstract

The main mechanisms by which obesity and overweight exacerbate heart  damage as a target-organ of arterial hypertension (HT), and also increase the risk of cardiovascular complications are discussed. Features  of the daily profile of blood pressure and features of the pathogenesis of HT in obesity are considered. The description of morphofunctional changes of the heart in patients with HT and obesity, in particular the development of left ventricular hypertrophy, is presented separately. Metabolic factors of cardiac remodeling in obesity (peculiarities of adipogenesis, correlation with the volume of epicardial adipose tissue, the role of adiponectin and leptin) are also described. In describing the disorders of elastic properties of the myocardium in obesity and HT, the authors focus on the changes in the global longitudinal systolic and circumferential strains in this category of patients.

699-705 349
Abstract

Oral anticoagulant (OAC) therapy is currently gaining special importance due to the significant spread of atrial fibrillation (AF) in the population (especially in older age groups). The use of OAC in AF has an extensive evidence base, which confirms a significant decrease in the number of strokes and total mortality in the context of anticoagulation therapy (ACT) in AF. Currently, the "gold standard" of the OAC is warfarin, which has proved effectiveness in all categories of patients with AF. A whole group  of new OAC (NOAC) also appeared. In Russia, dabigatran, rivaroxaban and apixaban have been registered. All NOAC were studied in randomized clinical trials (RCTs) in comparison with warfarin, mainly in patients with non-valvular AF, therefore, in valvular AF, as well as in patients with severe renal failure, warfarin remains the drug of choice. Advantages of warfarin in comparison with NOAC are the presence of known  antidote and standardized indicator of the efficacy and safety of the anticoagulation therapy – International Normalized Ratio (INR), as well as low price of the drug. The leading problem in the treatment of warfarin is the complexity and, at the same time, a strong  need to maintain INR within the therapeutic "window" of at least 60% of the treatment time. Obviously, the optimal solution to this problem is the possibility of self-testing of this indicator by the patient himself and,  probably, the ability to adjust the dosage of warfarin independently, to achieve the necessary values of INR (self-management) or titrate the dose with the help of a medical consultation by phone (self-monitoring). To date, several devices have been developed for self-monitoring of anticoagulation therapy – coagulometers. Their use leads to a decrease in the number of thromboembolic complications, and from the results of some RCTs – to a decrease in the number of large bleedings and total mortality, and to improve the quality of life of AF patients who  need  constant anticoagulation therapy. The high economic efficiency of using coagulometers has  also been  confirmed. Coagulometer CoaguChek  (Roche, Switzerland) has the largest evidence base for self-monitoring of INR and its impact on the efficacy and safety of anticoagulation therapy.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

706-715 349
Abstract

Recently, more and more attention has been  paid to the chronotherapy of arterial hypertension (HT). This method provides an opportunity to improve the treatment efficacy by non-traditional regimes of antihypertensive drug intake. The new findings concerning a high prognostic value of the night-time blood pressure (BP) and night BP fall stimulate the interest in chronotherapy of HT. This method is very easy to use, and the evidences of its high efficacy are growing. The advantages and limitations of two potential chronotherapy approaches are discussed in detail.

MAPEC was the largest project which investigated the possibility of cardiovascular complications risk reduction by normalizing the circadian rhythm of BP due to the bed-time administration of antihypertensive drugs. The authors obtained impressive results – more than a double reduction of cardiovascular complications risk in the chronotherapy group.  However, the study had serious limitations: ethnically homogeneous population, the lack of independent verification of endpoints and adverse  events,  and inconvenience of 48-hour BP monitoring.

The currently available scientific information concerning advantages of HT chronotherapy needs  further confirmation in the carefully designed multi-centre prospective studies. According to the authors’ opinion, illustrated by their original data, the relatively small and short studies are still important. Such trials allow using more nuanced methodological approaches, such as a double blind or cross-over design and comparison of the pharmacokinetics of antihypertensive drugs in the morning and evening administration.
716-724 454
Abstract

The opinion is expressed in some  domestic publications that  rivaroxaban has  the  most  favorable profile of drug  interaction in comparison with other new oral anticoagulants (NOAC). The basis for such judgments is the summary table of drug interaction from the Guidelines of the European Heart Rhythm Association 2015 on the use of NOAC in patients with non-valvular atrial fibrillation.

The paper discusses the issue that the abovementioned table contains some incorrect qualitative statements and quantitative data inconsistent with primary source  of information of NOAC drug interactions, and provides the updated and extended information on changes in NOAC plasma concentrations when  co-administered with drugs from the other  groups. On the basis of the presented data, the authors come to the conclusion that the profile of drug interaction of rivaroxaban does not differ significantly from these  of the other NOAC.

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