Vol 21, No 10 (2019)



Savenkov M.P., Ivanov S.N., Mikhailusova M.P., Palkin M.N., Okuneva I.N., Ivanova S.V.


Aim. To evaluate the efficacy, tolerability and safety of the drug Ekvapress (Gedeon Richter, Hungary) - a new fixed drug combination of ACE inhibitor lisinopril, diuretic indapamide with prolonged action and calcium channel blocker amlodipine in the treatment of patients with hypertension. Materials and methods. In 31 patients with high and very high cardiovascular risk of uncontrolled hypertension II-III degree without severe comorbid pathology using daily self-monitoring of blood pressure and diuresis (SCADDIUR) evaluated the results of a three-month application of a fixed combination of lisinopril (10/20 mg) with indapamide prolonged action (1.5 mg) and amlodipine (5/10 mg). Target BP reduction was achieved in all patients: in dose combination lisinopril 10 mg, indapamide 1.5 mg, amlodipine 5 mg, - in 87.1 percent of pts, with increased dose of lisinopril up to 20 mg - in 9.7% pots and in increased dose of amlodipine up to 10 mg - in 3.2% pts. The antihypertensive effect was characterized by daily circadian stability, accompanied by restoration of the initially disturbed day and night diuretic balance. The treatment was simple with respect to the selection of dosages of the components of the combination, well tolerated by patients, reduced the frequency of meteopathic reactions and did not cause the development of pronounced side effects. The positive properties of the drug combination are largely associated with the use of a prolonged form of indapamide diuretic. Conclusion. Equapress, fp a fixed combination of the ACE inhibitors lisinopril (10/20 mg), prolonged action diuretic indapamide (1.5 mg) and the CCB amlodipine (5/10 mg) has a high antihypertensive efficacy with circadian stability of action, good tolerability and safety of treatment, and also ease selection of the measuring components. Equapress can be used without prior separate titration of doses of components and is recommended for the treatment of patients with hypertension with high and very high cardiovascular risk. In most patients, the starting dose combination (lisinopril 10 mg/indapamide 1.5 mg/amlodipine 5 mg) is effective.
Consilium Medicum. 2019;21(10):9-16
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Mubarakshina O.A., Liubavskaia S.S., Somova M.N., Batishcheva G.A.


Aim. To provide data on main clinical and pharmacological parameters of angiotensin converting enzyme inhibitors (ACE inhibitors). Materials and methods. A review of national and foreign publications in the main search engines (PubMed, eLibrary, etc.) for the period 2000-2019 was conducted. Results. Prevention and effective treatment of cardiovascular diseases are a priority area of modern cardiology. Cardiovascular disease remains the leading cause of death worldwide. Arterial hypertension (AH) occupies the leading position among cardiovascular diseases, it is characterized by a severe progressive course, leads to other cardiovascular disorders, including chronic heart failure and chronic kidney disease, and also causes difficulties in the selection of therapy. The review presents data on the mechanism of action and clinical and pharmacological properties of ACE inhibitors, the main class of antihypertensive drugs, that affect the main link of pathogenesis of hypertension and cardiovascular complications, the renin-angiotensin-aldosterone system. This group of drugs has demonstrated a high efficacy at different stages of cardiovascular pathology in numerous clinical studies. The article presents a brief description of third-generation ACE inhibitor fosinopril, as well as the results of foreign and national studies proving its effectiveness and safety in patients with hypertension, chronic heart failure and chronic kidney disease with concomitant diabetes mellitus. The main difference between fosinopril and other ACE inhibitors is the dual route of elimination. This allows us to recommend the drug to patients with liver and kidneys disorders, as well as to elderly people without adjusting the dosage regimen and monitoring pharmacotherapy.
Consilium Medicum. 2019;21(10):16-19
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Adasheva T.V., Samorukova E.I., Akhmedyarova L.B., Odintsova D.V.


The article discusses the main principles of approaching the personalization of stable angina symptomatic therapy with a rationale for the choice of antianginal medications depending on clinical and pathophysiological phenotypes of the patient. This article summarizes the determinants and control of coronary blood flow and heart rate influence. Increased heart rate reduces the duration of diastole and thus coronary blood flow when metabolic vasodilation is no longer able to increase coronary blood flow. Increased heart rate also reduces the collateral blood flow. Association myocardial ischemia and myocardial contractile function is analyzed: reversible ischemic contractile dysfunction, myocardial hibernation, irreversible loss of regional contractile function. The clinical cases and the treatment modification according clinical phenotypes of the patient (stable ischemic heart disease with sympathetic activation and stable ischemic heart disease with heart failure decompensation) are discussed. Aspects of monotherapy and combined therapy for heart rate control and use of fixed combinations of antianginal medications are presented.
Consilium Medicum. 2019;21(10):20-26
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Kirichenko A.A.


Risk stratification of coronary events in 5 years performed at the basis of available non invasive stress tests helps in the choice of management tactics. Revascularization has a significant prognostic impact not only for high risk patients. As in patients with ischemic heart disease (IHD) heartbeat rate more than 70 per minute is an independent predictor of myocardial infarction development, high heartbeat rate is one of the therapeutic targets in secondary prevention. Blood pressure control in patients with arterial hypertension and IHD is also important as 25% of population risk of myocardial infarction development is determined by arterial hypertension. The advantage of low (75-150 mg) and medium (160-325 mg) doses of acetylsalicylic acid (ASA) in atherothrombotic complications prevention in patients with stable IHD has been proven. Enteric coating prolongs ASA release and absorption. Unlike simple ASA, only after repeated daily use of gastro-resistant tablets platelet cyclooxygenase acetylation is cumulated and results in sufficient decrease of its activity at the 6th day that results in significant inhibition of platelet function. Dyslipidemia correction and lipid profile parameters maintenance at target levels throughout lifetime significantly decrease cardiovascular mortality as a result of secondary prevention in all age groups both in males and females. If the target level of low density lipoproteins is not reached on statins use they can be combined with ezetimibe that inhibits cholesterol absorption in intestine. In patients with persisting high levels of low density lipoproteins despite adherence to a diet and use of as high as possible statins doses, use of medications from the group of PCSK9 inhibitors is indicated. The use of monoclonal antibodies to interleukin-1 р (canakinumab) in patients with stable IHD with C-reactive protein level more than 2 mg/l showed the importance of inflammation in development of atherosclerosis and its complications. Although suppression of body ability to develop inflammatory processes is highly effective in cardiovascuar events prevention if systemic inflammation is present, their use is unlikely to become routine in all patients groups as treatment with canakinumab was associated with increase of fatal infectious complications. It is recommended to patients with IHD to perform seasonal flu vaccination. For those who seek medical advice in first 2 days after flu symptoms development it is reasonable to use antiviral medications. Chronic inflammation as a key element of atherosclerosis pathogenesis can be associated not only with infectious and immune but also with metabolic factors that requires improvement of other organs and systems health, change of behavior and lifestyle.
Consilium Medicum. 2019;21(10):27-33
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Maznev D.S., Boldueva S.A., Leonova I.A., Shloydo E.A., Kochanov I.N., Kaledin A.L., Ardeev V.N.


Background. Manual thrombaspiration (MTA) is an adjunctive option during percutaneous coronary interventions (PCI) in acute coronary syndrome. Materials and methods. A total of 1597 case histories of patients with STEMI were studied. According to the character of the infarct-related artery lesion, the following patient groups were formed according to the coronary data: patients with subocclusive lesion/preservation of antegrade blood flow - 558 people (35%), patients with coronary thrombosis grade TIMI Thrombus Grade (TTG) 1-3 - 253 (16%) people, as well as a group of patients with thrombotic coronary artery occlusion with a degree of intracoronary thrombosis of TTG 4-5 (study group) - 786 (49%) patients. Patients of the study group were performed only primary PCI or PCI with adjunctive manual thrombaspiration. Results. Comparing the frequency of performing MTA in individuals of the study group (patients with thrombotic coronary artery occlusion with the degree of intracoronary thrombosis of TTG 4-5), it turned out that if in 2016 this procedure was performed in 48% of patients who had indications for its use, then in 2017 -only 28.8% (p<0.05). Analyzing data on the frequency of intraoperative and early postoperative complications, we can conclude that MTA in the studied hospitals is not associated with their more frequent development. It should also be noted that such a terrible complication as an intraoperative stroke occurred in the group of patients with MTA and without MTA with the same rate. Conclusion. Obviously, clearer clinical and angiographic criteria for selecting patients for MTA are needed, which will help make this procedure more effective. This thesis was voiced in the recommendations of the European Society of Cardiology of myocardial revascularization in 2018, where manual thrombaspiration is not recommended for use in routine practice, but it was noted that further study of this issue is necessary.
Consilium Medicum. 2019;21(10):34-38
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Trukhan D.I., Davydov E.L.


The current problem of public health is the optimization of drug therapy in patients with chronic heart failure and hypertension. Torasemide expands the use of loop diuretics in complex antihypertensive therapy due to a safe metabolic profile and multifactorial antihypertensive action. An urgent public health problem is the optimization of drug therapy in patients with chronic heart failure and arterial hypertension. Currently, the main indication for loop diuretics is chronic heart failure (CHF). The advantages of the torasemide loop diuretic compared to furosemide include: 1) torasemide is 4 times “stronger” in dosage; 2) a more stable (predictable) bioavailability, independent of food intake and the condition of the intestinal wall (relevant for congestive heart failure); 3) the half-life of torasemide (T1/2) is 4 times higher; 4) in chronic renal failure, T1/2 does not change (metabolism in the liver 80%); 5) additional effects of torasemide on renin-angiotensin-al-dosterone system - angiotensin II and aldosterone receptors. Due to its safe metabolic profile and multifactorial antihypertensive effect, torasemide expands the possibilities of using loop diuretics in complex antihypertensive therapy. The presence in the arsenal of the practitioner of the most famous drug torasemide allows optimizing drug therapy in patients with heart failure and arterial hypertension.
Consilium Medicum. 2019;21(10):40-47
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Platonov D.l., Iakovleva O.E., Bel'diev S.N., Il'in N.V., Tomskaia T.l., Ivanov K.I.


Pulmonary hypertension (PH) is a group of diseases characterized by a progressive increase of pressure in the pulmonary arteries and pulmonary vascular resistance, quickly leading to the right ventricular heart failure and patient death. Increasing interest in the PH problem is due to the lack of epidemiological data on the prevalence of PH, rapidly progressing diseases with severe complications and considerable mortality. If for some groups of PH (PH associated with the left heart failure or lung diseases) it all boils down to treatment and control of the underlying disease, for others (pulmonary arterial hypertension - PAH or chronic thromboembolic pulmonary hypertension - CTEPH), an attractive approach is the specific therapy, given the malignant nature of the course and the complexity of the pathogenesis of PAH. Riociguat is the first representative of a new class of PAH-specific drugs, indicated for the treatment of CTEPH, and some forms of PAH, an innovative drug that has shown a high survival rate for patients. The purpose of this article is to provide contemporary data on the management and treatment of patients, as well as the role of specific therapy and the place of riociguat in the treatment of patients with PAH and CTEPH.
Consilium Medicum. 2019;21(10):48-58
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Larina V.N., Bondarenkova A.A., Larin V.G., Vartanian E.A.


Aim. To provide up-to-date data on the feasibility, effectiveness and safety of prescribing ASA with the aim of primary prevention of cardiovascular and oncological diseases. Materials and methods. To write this review, a search was conducted for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, Medscape, etc.) for the last 0.5-11 years. The review included articles from peer-reviewed literature. Results. It is recommended that 75-100 mg of ASA be prescribed to patients with established cardiovascular diseases (CVD) and a 10-year risk of myocardial infarction in excess of 20%. The question of the appropriateness and safety of prescribing ASA in people with moderate and low risk remains open. Many experts oppose the prescription of ASA in these patients, citing the high risk of hemorrhagic complications and the lack of a positive effect. The risk of bleeding does not depend on the dose directly, which requires further study of the effectiveness of different dosages of ASA, depending on body weight. However, when prescribing an ASA, it is important to consider the gender, age, body weight of the patient, and the co-morbidity. There are numerous opinions about the benefits of prescribing ASA in people at low risk, including with regard to the antineoplastic effect. Conclusion. Based on the results of numerous studies, the question of the feasibility of primary prevention of CVD and colorectal cancer is ambiguous and requires further study.
Consilium Medicum. 2019;21(10):59-66
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Leonova M.V.


Background. Statins are widely used in clinical practice in cardiovascular disorders treatment. Along with this in 2012 Food and Drug Administration released a statement about rare cognitive disorders in some patients that were associated with statins use according to postmarketing reports. The decision was made to include mild and reversible cognitive side effects in product instructions. Alongside that active study of statins influence on cognitive functions for evaluation of clinical significance and risk factors of these adverse effects is going on. Objective. To present scientific literature review of statins influence on cognitive functions in different levels of evidence. Materials and methods. A literature search for foreign publications was performed in international search systems (PubMed and others) from year 1999 in order to write the review. The review is based on analysis of large observational and randomized clinical studies (RCS) as well as several metaanalyses of statins influence on cognitive function evaluation. Results. Since year 2000 publications on series of cases on neurocognitive disorders development after statin use have emerged. The disorders were presented mostly by transient or short amnesia or also by other symptoms (depression, joylessness, despair, aggression, anxiety, psychic tension, irritability, increased emotional reactivity, loss of interest in activities, in communication, or even suicide behavior). Cognitive disorders were observed after several months of treatment with statins of after dosage increase and were reversible after discontinuation of statins therapy. Further a number of retrospective case-control studies and prospective cohort studies of statins influence on cognitive function were performed. Most of them showed statins protective effect on dementia development in patients with Alzheimer disease and in patients with normal cognitive function. In some RCS taking account of cognitive functions as secondary outcomes no significant risk of cognitive function decrease or dementia development as well as no improvement in patients diagnosed with dementia after statins use were observed. Metaanalyses of observational studies and RCS did not also show negative impact of statins on cognitive function and dementia development. Conclusion. The present data supports the hypothesis that statins are partly related both with reversible cognitive side effects and with dementia risk decrease. More RCS are necessary for final decision on statins global impact on cognitive function and determination of individual risk factors.
Consilium Medicum. 2019;21(10):67-73
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Mubarakshina O.A., Somova M.N., Batishcheva G.A.


Aim. To provide a scientific review of current data on pharmacogenetic aspects of antithrombotic therapy with warfarin. Materials and methods. To write this review we conducted searching for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) since 2000. Results. In recent years a social and economic relevance of thrombotic complications in patients with cardiovascular diseases is steadily increasing. The major drugs for long-term, in some cases life-long, thromboprophylaxis are oral anticoagulants. Despite the appearance of novel direct acting oral anticoagulants on the pharmaceutical market, vitamin K antagonist warfarin does not lose its position. In a number of clinical situations this drug has no alternative. Disadvantages of warfarin include its narrow therapeutic index and therefore the need for careful continuous laboratory monitoring of the blood coagulation system. An overdose of warfarin can cause serious bleeding complications which develop more often at the beginning of treatment. For this reason, a personalized approach to selecting the initial warfarin dose is of particular importance. When selecting the drug dose along with clinical factors genetic ones are also of great importance. The presence of genetic polymorphisms in genes that control warfarin pharmacokinetics and pharmacodynamics can be decisive. Warfarin dosing algorithms are available, however, new data that are recently emerging, dictate the need for their modification, including taking into account ethnic characteristics of patients. Different ethnic groups have features in a contribution of various genes and genetic polymorphisms to manifestation of warfarin’s anticoagulant effect. It was shown that identification of CYP4F2 genetic polymorphisms in African- Americans is not necessary, whereas for Europeans it is a prerequisite. At the same time, determining genetic variants of CYP2C rs12777823 is important for African Americans, but it should not be determined for Europeans. Conclusions. Warfarin remains one of the most commonly prescribed anticoagulants in routine clinical practice. Its safety is ensured by individual selection of initial and maintenance doses by use of algorithms based on clinical and genetic factors. The emergence of new data on warfarin pharmacogenetics allows to personalize the drug dosing to the maximum, which ensures the efficacy and safety of anticoagulant therapy.
Consilium Medicum. 2019;21(10):74-78
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Erlihr A.D.


This article provides a small excursion into the history of dual antiplatelet therapy (DAT) as well as main points of modern approaches to its use. Based on completed randomized clinical trials it also makes an assumption about how approaches to DAT can change in the future. DAT as a combination of acetylsalicylic acid (ASA) and one of the P2Y12 receptor inhibitors (clopidogrel, prasugrel or ticagrelor) has been used in clinical practice for almost 20 years, its use is mainly recommended at the earliest stage of acute coronary syndrome (ACS) or at planned coronary stenting. Two main questions have always been related to DAT: the choice of drug for DAT and the duration of DAT. If the first question is now almost resolved (ticagrelor or prasugrel combined with ASA are preferred in most cases of ACS and clopidogrel combined with ASA is preferred for planned stenting), then the problems of DAT duration continue to be discussed. Current view on DAT can be described by the word "individualization", which means making a separate decision on the duration of DAT depending on the patient's characteristics and on the ratio of hemorrhagic and ischemic risks. To facilitate the decision on the duration of DAT the use of standardized PRECISE-DAPT and DAPT scales is currently recommended. Their values allow us to conclude what DAT duration is safe and effective. The data from the completed clinical studies STOP-DAPT-2 and SMART-CHOICE suggest that in the near future DAT duration will be shortened. In both of these studies, the shorter DAT was superior to the DAT of standard duration in terms of safety criteria and was comparable to it in terms of effectiveness. Another important change, as it seems, should be expected in the basic rules of antithrombotic treatment after coronary stenting in patients with atrial fibrillation. In this case, the need to combine DAT with oral anticoagulant (OAC) is associated with a worse prognosis due to the high probability of bleeding. Several studies with relatively similar design - PIONEER-AF, RE-DUAL-PCI, and especially AUGUSTUS - showed that from the first days after coronary stenting the combination of any of non-vitamin K antagonist OACs with a P2Y12 inhibitor (without ASA) may be safer and no less effective treatment option compared to the "triple" therapy (DAT + OAK).
Consilium Medicum. 2019;21(10):79-84
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Doshchitsin V.L., Syrov A.V., Pavlova T.V.


Arrhythmia treatment is one of the most difficult problems in cardiology. The lack of evidence base determines the difficulty of choosing an antiarrhythmic drug (AAP) in a particular clinical situation, does not allow to fully assess the need and safety of treatment. The analysis of key studies on antiarrhythmic therapy (AAT). Detailed information on the properties, indications, contraindications, efficacy and safety of drugs widely used in Russian clinical practice, which include propafenone, amiodarone, sotalol, lappaconitine, is presented. A practical approach to the choice of AARP in various types of arrhythmias in patients without and with a pronounced organic lesion of the heart to which with regard to AAT include: unstable ischemic heart disease, myocardial infarction, low left ventricular ejection fraction <40% and left ventricular hypertrophy >15 mm. The special role of propafenone having 2 forms of oral and infusion has been analyzed. Having an evidence base makes it possible to use this drug to treat a wide range of arrhythmias, in particular, to relieve paroxysmal atrial fibrillation by the patient ("pill in pocket"), by outpatient physicians, emergency medical team and hospital in patients without pronounced organic heart disease.
Consilium Medicum. 2019;21(10):86-94
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Ostroumova O.D., Goloborodova I.V.


QT interval prolongation is associated with an increased risk of life-threatening ventricular arrhythmias (including polymorphic ventricular tachycardia, also called torsades de pointes) and sudden cardiac death. One of the most common causes of acquired QT interval prolongation is the effect of certain drugs. To date, almost all existing drug groups have representatives with QT-lengthening effect, the realization of which, especially when combined with the so-called risk factors for QTC lengthening (modifiable - bradycardia, electrolyte abnormalities, drug interactions, overdose of QT-lengthening drugs and non-modifiable - female gender, older age, hereditary conditionality, the presence of structural heart disease, liver and/or kidney disease), leads to the development of clinically significant manifestations and complications associated with QTc prolongation, including fatal. Most pronounced QT-lengthening effect has representatives of anti-arrhythmics (IA, IC and class III), antipsychotics, antidepressants, antibiotics (macrolides and fluoroquinolones), antihistamines, anticancer and antifungal agents, prokinetics, lipid lowering drugs and diuretics, excluding potassium-sparing. Awareness and adequate assessment of the potential QTc prolongation ability of a drug administered to a patient, monitoring and correction of factors that determine and increase the risk of drug-related of the QTc prolongation, ECG monitoring, as well as the complete elimination of all drugs that potentially cause the QT interval prolongation, - the most important therapeutic and prophylactic measures to prevent or to stop the arrhythmogenic drugs effects.
Consilium Medicum. 2019;21(10):95-106
pages 95-106 views


Leonova M.V.


Aim. To provide a scientific review on an unfavorable effect of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes (high blood pressure (BP), myocardial infarction, stroke, heart failure, atrial fibrillation), which can be united by the term of “cardiotoxicity”. Outcomes and methods. To write this review we searched for publications in Russian and international search engines (PubMed, eLibrary, etc.) since 1993. The review is based on an analysis of large clinical and observational studies and meta-analyzes, which is of great importance in the evidence of the data. Results. NSAIDs are widely used drugs in clinical practice. Along with the well-known gastrointestinal side effects of NSAIDs, a large group of adverse effects are cardiovascular events, which were referred to as “cardiotoxicity” in the 2000s. It was shown that cardiotoxicity of NSAIDs can be determined by the degree of selectivity to the action of cyclooxygenase (COX) -2 and has a dose-dependent and course effect for many drugs. According to a number of meta-analyzes and large clinical and observational studies (registers), the use of NSAIDs can lead to an increase in blood pressure (more than 5 mm Hg) and arterial hypertension (from 10 to 29%), and also counteracts the hypotensive effect of antihypertensive drugs ( p-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists). According to large meta-analyzes, NSAIDs increase the risk of myocardial infarction, stroke, decompensated heart failure, atrial fibrillation, and mortality. These risks are showen both for selective COX-2 inhibitors - coxibs (rofecoxib, etoricoxib) and traditional non-selective NSAIDs (diclofenac, ibuprofen, indomethacin). However, celecoxib has an advantage of reducing the risk of cardiovascular outcomes over other NSAIDs. The unfavorable effect of NSAIDs on cardiovascular outcomes increases with doses or frequency of administration and is seen even with short-term use (less than 7 days), and also increases with high cardiovascular risk. Conclusions. The results of this review showes that in clinical practice there is no obvious safe therapeutic window for NSAIDs, that justifies the need for limited use of NSAIDs, especially in patients with established cardiovascular disease.
Consilium Medicum. 2019;21(10):107-116
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Biryukova E.V.


Diabetes mellitus (DM) is an urgent problem of modern medicine. This disease is associated with vascular events that determine the prognosis of patients' lives (nephropathy, retinopathy, damage to great vessels of the heart, brain, arteries of the lower extremities). Achieving glycemic control plays a key role in preventing these complications. Current clinical guidelines on patient treatment which offer an approach of an individualized choice of therapy goals by glycated hemoglobin (HbA1c) based on the patient's age, life expectancy, presence of atherosclerotic cardiovascular disease and the risk of severe hypoglycemia are discussed. To determine the individual level of HbA1c in elderly patients, these principles imply a simple division into functionally independent and functionally dependent individuals. The role of self-control of glycaemia is emphasized as the basis for the effectiveness of ongoing hypoglycemic therapy and the prevention of hypoglycemia, the frequency of self-control is discussed. The key role of glycemic self-control for the efficacy of glucose-lowering therapy and prevention of hypoglycemia is emphasized and the frequency of self-control is discussed. Important criteria for choosing a glucometer are compliance with accuracy standards, simplicity and ease of use, ease of obtaining results, which allows patients of any age to take measurements of blood glucose levels. With the development of technology, new “smart” glucometers have appeared, which, thanks to integration with a free mobile application (available on the Internet), enable remote monitoring and significantly expand the capabilities of managing diabetes.
Consilium Medicum. 2019;21(10):117-121
pages 117-121 views

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