[Personalized approach for direct oral anticoagulant prescription: from theory to practice].

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

[Prevention of thromboembolic and hemorrhagic events in patients with atrial fibrillation undergoing elective surgery]. / Profilaktika tromboémbolicheskikh i gemorragicheskikh oslozhnenii u patsientov s fibrilliatsiei predserdii pri provedenii planovogo khirurgicheskogo lecheniia.

OBJECTIVE: To compare incidence of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF) undergoing elective surgery on different schemes of perioperative anticoagulant therapy (ACT). MATERIAL AND METHODS: There were 86 patients (56 (65.1%) men and 30 (34.9%) women, mean age was 69 (64; 78) years) with non-valvular AF who underwent elective interventions. Forty (46.5%) patients underwent abdominal surgery, 34 (39.5%) - cardiovascular procedures, 12 (14.0%) patients underwent surgery for malignant diseases. We have analyzed incidence of thromboembolic and hemorrhagic events and compliance of perioperative ACT modes with current international guidelines. RESULTS: Thromboembolic and hemorrhagic events developed in 14 (16.3%) patients. Thromboembolic complications were noted in 6 (7.0%) patients, hemorrhagic events - in 8 (9.3%) cases. Maximum complication rate was observed in case of bridge-therapy (n=12, 20.0%). Cancellation of ACT was followed by 2 (9.5%) complications, bridge-therapy - by 4 (6.7%) thromboembolic complications. Hemorrhagic events were 2 times more common in case of this therapy (n=8, 13.3%). It was found that ESC guidelines for perioperative ACT were applied in less than half of patients (41, 47.7% patients with AF undergoing elective surgery). Half of complications (8 out of 16) occurred if unapproved modes of ACT were used (including 7 cases of bridge-therapy was not necessary). The causes of these complications were inadequate assessment of perioperative risk of thromboembolic and hemorrhagic events; unreasonable administration of bridge therapy. CONCLUSION: An unambiguous clinical effect of bridge therapy has not been confirmed in patients with high risk of thromboembolic complications. Cancer patients have higher risk of complications compared with others. These events occur mainly due to non-compliance with clinical guidelines and insufficient prevention of thromboembolic events.

[Direct oral anticoagulants in atrial fibrillation patients aged 75 years or older: Efficacy and safety balance]. / Priamye peroral'nye antikoagulianty u patsientov s fibrilliatsiei predserdii v vozraste 75 let i starshe: balans éffektivnosti i bezopasnosti.

Atrial fibrillation (AF) is one of the most common heart rhythm disorders in the population. Researchers revealed a direct relationship between their incidence and a patient's age long ago. One of the most challenging issues of clinical practice in patients with AF is anticoagulant therapy used in the so-called very elderly patients aged 75 years and older when age itself is a risk factor for developing both thromboembolic and hemorrhagic events due to anticoagulants, regardless of the mechanism of action of the latter. However, scientific data regarding the treatment and prevention of thromboembolic events in elderly and senile patients with AF are very scarce and often uninformative. The data from the EURObservational Research Programme-Atrial Fibrillation Registry Pilot Phase (EORP-AF Pilot) and the randomized clinical studies RELY, ROCKET AF, ARISTOTLE, and AVERROES were analyzed to identify the most safe and most effective anticoagulant for elderly patients (over 75 years). Relying on the analyses of literature data, the authors propose an algorithm based on clinical characteristics for choosing the anticoagulant for patients older than 75 years.

[Anticoagulant therapy in patients with atrial fibrillation and reduced kidney function of diabetic and non-diabetic etiologies]. / Antikoaguliantnaia terapiia u patsientov s fibrilliatsiei predserdii i snizhennoi funktsiei pochek diabeticheskoi i nediabeticheskoi étiologii.

AIM: To evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and stages I-III chronic kidney disease (CKD). SUBJECTS AND METHODS: The cohort parallel-group study included 92 patients with AF and stages I-III diabetic and non-diabetic CKD, who were treated with DOACs (dabigatran, rivaroxaban, or apixaban) and vitamin K antagonists (warfarin). The follow-up duration was 12 months. RESULTS: Thromboembolic events and bleeding, which required patient hospitalization or blood transfusions, were not recorded during 1-year follow-up. There was no clinically significant progression of CKD in the groups of therapy with vitamin K antagonists or DOACs. Just the same, a more intense decrease in glomerular filtration rate and a high rate of hemorrhagic complications were revealed in the subgroup of patients with diabetes mellitus (DM) versus those with non-diabetic CKD. CONCLUSION: In patients with non-valvular AF and diabetic and non-diabetic CKD, the use of DOACs effectively and safely prevents thromboembolic events, irrespective of the stage of CKD. At the same time, in patients taking anticoagulants, CKD progresses more rapidly in the presence of DM than in its absence, regardless of a specific anticoagulant. Hemorrhagic complications are more common in patients with AF, DM, and CKD, which requires more frequent monitoring of their kidney function.

[The new 2017 European society of cardiology (ESC) guidelines: important changes for introduction into clinical practice]. / Novye rekomendatsii Evropeiskogo obshchestva kardiologov (ESC) 2017 g.: vazhnye izmeneniia dlia vnedreniia v klinicheskuiu praktiku.

The paper gives an overview of the European Society of Cardiology (ESC) guidelines updated in 2017. The revised and amended guidelines for areas, such as dual antiplatelet therapy (DAT), treatment of patients with ST-segment elevation myocardial infarction (STEMI), and management of patients with valvular heart disease and peripheral artery disease, were presented in late summer of this year. The authors of this paper present an independent analysis and discussion of new data on the key issues of diagnosis and treatment in patients in the above areas. The recommendations on DAT pay special attention to the timing of the therapy and to the choice of its drugs. The updated data on the treatment of patients with STEMI accurately determine the time to percutaneous coronary interventions, approaches to revascularization; the updates touch upon fibrinolytic therapy and new approaches to lipid-lowering therapy too. Recommendations for the management of patients with peripheral artery atherosclerosis propose for the first time a section devoted to the choice of antiplatelet therapy (an antiaggregant and/or an anticoagulant) depending on the clinical situation.

[Natriuretic Peptides: Role in Current Cardiology].

Natriuretic peptides were discovered in 50-70s of the XX century. BNP was more diagnostically and prognostically significant, as it is secreted directly into the ventricles of the heart. The studies demonstrated a high predictive value of increasing the level of BNP in acute decompensation of heart failure and in patients with chronic heart failure in a study of Val-HeFT It was demonstrated that monitoring the level of NT-proBNP can be used for the selection of optimal therapy, affect the course and outcome of the disease, and reduce the cost of treatment. The next step in learning BNP was to undertake attempts of their use in the therapy of heart failure. Long-term therapy BNP (drug nesiritide) improved left ventricular remodelling in patients with stable heart failure. Currently the definition of the levels of BNP and NT-proBNP is used for the diagnosis and management of patients with heart failure.

[Depression and cardiovascular diseases].

Depression is considered to be an independent cardiovascular risk factor and it may worsen the symptoms of already established cardiovascular pathology such as coronary heart disease, chronic heart failure, stroke and hypertension. 3 key psychobiological mechanisms by means of which depression influences cardiovascular system: disbalance in stress response of endocrine system, hyperregulation of autonomic nervous system and immune disorders leading to dysregulation of acute phase proteins and proinflammatory cytokines release. In majority of studies in patients with depression and cardiovascular diseases it was shown that antidepressants improve the symptoms. By the way, in some studies controversial results were obtained. Future studies in this direction with involvement of cardiologists and psychiatrists should be held.

[Therapy with perindopril: organoprotection, not just the antihypertensive effect].

Perindopril is one of the most prescribed inhibitors of angiotensin converting enzyme, has a large evidence base, which allows to use it in patients with hypertension, diabetes mellitus type 2, coronary heart disease and chronic heart failure. In this review, the author focused on the evidence of organoprotecting properties of perindopril that lie outside lowering blood pressure.

[Age-related changes in saccadic eye movements in healthy subjects and patients with Parkinson's disease].

Age-related changes in characteristics of saccadic eye movements (latency, duration and percentage of multistep saccades) in healthy subjects and patients with Parkinson's disease were evaluated. Healthy volunteers were divided into 6 age groups (17-20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-75 years), parkinsonian patients into 3 age groups (41-50 years, 51-60 years, 61-75 years). According to our data, saccade characteristics depend upon age in both healthy subjects and parkinsonian patients. In healthy volunteers the percentage of multistep saccades and the mean saccade latency increase significantly after the age of 60. Values of these characteristics in patients with Parkinson's disease significantly exceed the values in the corresponding age groups of healthy subjects. The "disease" factor (MANOVA) has a greater influence on saccade latency and percentage of multistep saccades then the "age" factor. The duration of single saccades depends on age to a smaller extent and does not change in patients with Parkinson's disease. The peculiarities of neurodegenerative processes during normal aging and aging with Parkinson's disease are discussed.

[Prevalence and structure of anemia in patients with chronic heart failure in a therapeutic hospital].

We carried out retrospective analysis of 219 case histories of patients with chronic heart failure admitted to a general medical hospital. Anemia (hemoglobin level below 130 g/l in men and below 120g/l in women) was found in 23.3% of cases. Anemia was classified as iron deficiency in 23.5% and as B12 deficiency in 3.9% of patients. In 3.9% of patients other definite causes of anemia were found and in 68.6% origin of anemia was not determined. However at least in some of the latter patients disturbed kidney function could play some role in anemia genesis.

[Effect of dopamine deficiency on the preparation of visually guided saccadic eye movements].

Parameters of saccadic eye movements were studied in patients with Parkinson's disease and control subjects. In parkinsonian patients, the number of slow regular saccades was shown to be increased, and the number of express saccades was shown to be decreased. As a result the mean of saccade latency in patients was longer than in the control group. Moreover, the percentage of multistep saccades in patients with Parkinson's disease. In this case, not one but two or three saccades were performed with smaller amplitude to the target. We point, that the multistep saccades occurred mainly among the express saccades. Obviously, the dopamine deficiency distinguishing parkinsonian patients takes the primary part in the development of saccadic disorders. Degeneration of the nigrostriatal dopamine pathway results in imbalance in activity of the direct and indirect output pathways of the striatum. We suppose that this leads to inhibition of neurons activity in the superior colliculus during the saccade performance, which results in the early saccade interruption. In support of this reasoning, the mean of saccade latency and the percentage of the multistep saccades decreased in patients with Parkinson's disease after dopamine D2/D3 agonist (piribedil) treatment, due to activity restoration of the indirect pathway.

[THe characteristics of the autonomic reactions of healthy adolescents and of those with lowered intellectual productivity]. / Osobennosti vegetativnogo reagirovaniia podrostkov--zdorovykh i so snizhennoi intellektual'noi produktivnost'iu.

Present research is devoted to psychophysiological study of the mechanisms of functional state control in normal and educationally disabled children using EEG, neuropsychological, and heart rate data obtained during different types of mental activity, including performance of arithmetic, verbal, spatial, and time-perception tests. Attention index and one-minute time interval production in the group of educationally disabled patients were found to be statistically lower than in the normal children. Heart rate level in this group was also lower than in the normal children of the same age. Increase of heart rate indices during perception of instruction and transition to its realization was statistically higher in the group of normal children. The differences between the groups can be explained by disfunction of the functional state regulation mechanisms, deficit of sympathetic influence and prevalence of parasympathetic ones, as well as by the weakness of the functions of the nervous system which causes disadaptation in educationally disabled children.

[Assessment of efficacy of combined therapy with antihypertensive agents and biguanides in patients with metabolic syndrome]. / Otsenka éffektivnosti kompleksnoi terapii antigipertenzivnymi sredstvami i biguanidami u bol'nykh s metabolicheskim sindromom.

To compare effects of antihypertensive and combined therapy on 24-hour blood pressure, biochemical parameters and chronic hyperinsulinemia in patients with metabolic syndrome. 54 patients with metabolic syndrome were observed during 8 weeks. 28 patients (group A) were treated with antihypertensive agents (calcium antagonists, and when required -- ACE inhibitors and diuretics). 26 patients (group B) received the same therapy plus metformin. There were no significant changes in parameters of lipid and carbohydrate metabolism in group A. In group B we found significant decrease in C-peptide (p<0.05) and triglyceride (p<0.1) levels and increase in high density lipoprotein cholesterol levels (p<0.01). The combined antihypertensive and metformin therapy has a significant effect on carbohydrate and lipid metabolism.

[Metabolic syndrome from the point of view of a cardiologist: diagnosis, non drug and drug treatment]. / Metabolicheskii sindrom s tochki zreniia kardiologa: diagnostika, nemedikamentoznye i medikamentoznye metody lecheniia.

Timely diagnosis and treatment of metabolic syndrome is important because of high prevalence of this pathology in population. For the elaboration of approaches to complex treatment of this syndrome it is necessary to understand pathogenetic mechanisms of development of hypertension and metabolic changes as well as acquire an array of non drug and drug methods of influence on elevated blood pressure and disordered carbohydrate, lipid and purine metabolism. Phenylalkylamine calcium antagonists should be used as drugs of choice for treatment of hypertension. These agents exert slowing of heart rate, coronarolytic and antiatherogenic effects, the latter being especially important in this group of patients. Resistance of hypertension to treatment developing on the background of insulin resistance of peripheral tissues dictates necessity of the use of combinations of antihypertensive drugs with consideration of their metabolic effects. For correction of metabolic changes metformin is used in addition to non drug methods which include diet and exercise. Treatment with metformin allows to decrease insulin resistance and thus severity of derangements of metabolism.