Vol 21, No 1 (2019)

Aim. To present the fundamental standpoints of renewed 2018 European guidelines for the management of arterial hypertension and to discuss aspects of its use in real-life clinical practice with due consideration of Russian experts opinions. Materials and methods. 2018 European guidelines for the management of arterial hypertension and Russian Society of Cardiology Memorandum on these guidelines are discussed. Results and conclusion. Fundamental standpoints of 2018 European guidelines for the management of arterial hypertension as well as essential and important in context of real-life clinical practice changes in comparison with the previous revision are presented. Much attention is given to risk factors and associated with hypertension organ damage detection. Special focus is made on the main principle of blood pressure pharmacological control - “one pill strategy”. A step to step regimen for prescription of combined antihypertensive therapy where renin angiotensin aldosterone system (RAAS) inhibitors are first line medications is presented. At the first stage the choice combination includes angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker and dihydropyridine calcium channel blocker or diuretic. It is outlined that for the first time in the guidelines the use of 3-component antihypertensive therapy in the form of “one pill” is emphasized and its actual components are specified (RAAS inhibitor, calcium channel blocker and diuretic). Also a small subset of patients in whom it is possible to use antihypertensive medications in monotherapy is described. The management of elderly and very elderly patients and patients with senile asthenia syndrome is described. Target blood pressure levels depending on comorbid disorders existence such as diabetes mellitus, chronic kidney disease, ischemic kidney disease, stroke and/or transient ischemic attack as well as patient age are discussed. All standpoints of European guidelines for the management of arterial hypertension are discussed from the point of view of Russian experts that is presented in Russian Society of Cardiology Memorandum. The second part of the article presents possibilities of one pill strategy use in combined antihypertensive therapy based of valsartan and discusses the importance of patients’ compliance to blood pressure pharmacological control and ways of improving this compliance.

Aim. To present a scientific review of angiotensin II (AT II) receptor blockers (sartans) clinical pharmacology, in particular pharmacologic and clinical characteristics of candesartan. Materials and methods. A literature search for Russian and foreign publications since year 1999 was conducted in Russian and international databases (PubMed, eLibrary and others) in order to write this review. Results. In the last years AT II receptor blockers or sartans have been widely used for arterial hypertension treatment. Despite general characteristics of this antihypertensive medications group such as mechanism of action, possibility of administration one time a day, good tolerance, and minimal adverse effects, there are clinical and pharmacological differences between medications that determine their effectiveness. It is shown that candesartan kinetics of interaction with AT receptors is specific, that results in more expressed hypotensive effect and high trough/peak index of hypotensive effect. Candesartan pharmacokinetics and hypotensive effect do not depend on CYP2C9 metabolizing ferment genetic polymorphism. According to several metaanalyses results candesartan has advantages in level of blood pressure (BP) decrease that results in BP-dependent advantages. In a large observational study candesartan showed better results of influence on arterial hypertension cardiovascular outcomes in comparison with losartan, that demonstrates possible BP-independent clinical and pharmacological advantages. At present sartan therapy is becoming more affordable because of generics development. Hyposart (manufacturer - pharmaceutical company Polpharma, Poland) has an acknowledged place among candesartan generics. It has shown complete equivalence to original medication in bioequivalence studies, what is important in evidence-based medicine. Conclusion. Candesartan is one of the most powerful medications of AT II receptor blockers group that is proved by its clinical and pharmacological characteristics. Advantages of its hypotensive effect and long-term effectiveness were demonstrated in several studies and metaanalyses and are associated with BP-dependent and BP-independent effects determined by receptor interaction characteristics.

Aim. To study possibilities of non-invasive electrophysiological methods (microvolt Т-wave alternance - mTWA) heart rate turbulence (HRT), deceleration capacity (DC) use in stratifying risk of arrhythmic events and mortality in patients with ischemic heart disease (IHD) and implantable cardioverter-defibrillator (ICD). Materials and methods. The study included 45 patients with verified IHD diagnosis and indications for ICD implantation. In all patients serum creatinine level, glomerular filtration rate (GFR), and serum lipid fractions were determined and 24-hour Holter electrocardiogram (ECG) monitoring was performed where HRT, mTWA, and DC as well as acceleration capacity (AC), and heart rate variability (HRV) were determined. Survived patients were followed-up for no less than 30 months (mean follow-up 48 [42; 51] months, maximum - 70 months). The study endpoints were death from any cause and “arrhythmic” endpoint (appropriate ICD discharge or sudden cardiac death - SCD). Results. Ten (22.2%) patients died from different causes during follow-up period. Arrhythmic endpoint (appropriate ICD therapy or SCD) was observed in 13 (28.9%) cases. Significant differences in DC, CRT, and serum creatinine level were observed in patients who survived and died. No patients with normal CRT or in low-risk group died during follow-up. There were significant differences in number of ventricular extrasystoles (VES) morphologies according to 24-hour Holter ECG monitoring and in serum cholesterol level in patients with or without arrhythmic events. Multifactor regression analysis showed serum creatinine level to be an independent risk factor of lethal outcome, and both polytope VES and serum cholesterol level were shown to be independent predictors of arrhythmic endpoint. Conclusion. Non-invasive electrophysiological markers have demonstrated high negative significance in lethal outcome prognosis in patients with IHD and ICD. Serum creatinine level was shown to be the only independent lethal outcome predictor. Polytope VES and serum cholesterol level were demonstrated to be independent predictors of arrhythmic endpoint.

Aim. To present modern view on the role of mineralocorticoid receptor antagonists (MRA), eplerenone in particular, in treatment of patients with post-infarction cardiac failure, and to analyze its effectiveness and safety. Materials and methods. Data fr om scientific sources published in Russia and abroad in 1984-2018 years were analyzed. Conclusion. Acute myocardial infarction with congestive cardiac failure (CCF) development is associated with sympathoadrenal system and renin-angiotensin-aldosterone cascade hyperactivation that results in pathologic myocardium remodeling following fibrosis. Within the concept of quality of life improvement and lifetime increase in patients after myocardial infarction it is important to prescribe MRA, eplerenone in particular, besides renin-angiotensin-aldosterone system inhibitors and b-adrenoblockers (b-AB). Accumulated data on MRA effectiveness in patients with CCF including patients after myocardial infarction is the basis for inclusion of these medications in National guidelines on CSF diagnostics and treatment of Russian Society of Cardiology and Russian Scientific Medical Society of Therapists. According to these guidelines medications of this group are recommended (level IA) to the use (combined with angiotensin-converting enzyme inhibitors - ACE inhibitors and b-AB) in all patients with medium severe and severe CHF who have decreased contractile function of left ventricle in order to decrease mortality risk and readmission frequency and to improve symptoms. A similar point of view is presented in European Society of Cardiology guidelines wh ere MRA also have IA level of evidence to the use as a first line medication (together with ACE inhibitors and b-AB for CHF treatment). The presented clinical case supported by the evidence of previously conducted studies demonstrates the leading role of eplerenon in therapy that results in prognosis improvement in patients with CHF after myocardial infarction who have low left ventricular ejection fraction.

Aim. To evaluate the significance of potassium and magnesium in human health formation and their role in development of functional disorders of cardiovascular and nervous system and in development and progression of cardiovascular diseases. Materials and methods. Data from 55 literature sources published in Russia and abroad in the period of 1972-2018 years are reviewed. Results. Potassium has an important role in cells bioelectrical activity organization, cell action potentials formation and neuromuscular excitability and conductibility sustentation. Hypokalemia symptoms can be quite various. Frequent ones include neuromuscular conductibility disorders, various changes in cardiovascular system (myocardial contractile function decrease, blood pressure (BP) decrease, cardiac cavities dilatation). Potassium intake increase is followed by lower incidence of cardiovascular and cerebrovascular events, new cases of diabetes mellitus (DM) type 2, left ventricular hypertrophy, cardiac insufficiency, and arrhythmias. Magnesium is a universal regulator of biochemical and physiological processes in the body, a cofactor of more than 300 enzymes participating in biochemical reactions, and a natural physiologic potassium antagonist. It reduces potassium release from sarcoplasmic reticulum and protects cells from potassium overload in conditions of ischemia. Therefore magnesium reduces systemic and pulmonary vascular resistance that results in systemic BP reduction and moderate cardiac index increase. Also reliable evidence indicating moderate but clinically significant antihypertensive effect of magnesium medications was received. Magnesium deficiency is associated with increase of total cholesterol level, low-density lipoprotein, and triglycerides. Serum magnesium level is inversely proportional to the degree of cardiovascular disorders development risk, particularly of cardiac rhythm disorders and IHD complications. European Food Safety Authority (EFSA) confirmed that patients’ health status improved after a period of magnesium adequate intake. Even severe hypokalemia and hypomagnesemia often remain non-diagnosed in clinical practice. Medical practitioner of any kind should remember of potassium and magnesium deficiency clinical manifestations in order to manage it or prevent its development in patients with risk factors by adequate treatment assignment. Described potassium and magnesium interrelations as well as relatively high frequency and severity of combined deficit of these macronutrients justify advisability of the use of combined medications containing К+ and Mg2+in treatment of many disorders. An additional effect is observed when these electrolytes levels are corrected together. Conclusion. Control of electrolyte balance, first of all, of potassium and magnesium balance, should be an intrinsic part of present day clinical practice. In patients with high risk of hypokalemia and hypomagnesemia development either its correction in case of detection or prevention of potassium and magnesium deficiency development should be performed. Potassium and magnesium balance maintenance provides additional therapeutic effect in patients with AH, DM, congestive heart failure, IHD (including myocardial infarction), as well as in patients with high risk of stroke or severe ventricular arrhythmia development.

Background. According to present 2016-2017 recommendations, propafenone and amiodarone are the main antiarrhythmic medications (AAM) for medicamentous sinus rhythm (SR) restoration. Direct effectiveness and safety comparison of these medications injectable forms for atrial fibrillation (AF) paroxysm treatment on pre-hospital stage is one of the pressing issues. Aim. To compare effectiveness and safety of propafenone and amiodarone use in urgent SR restoration in patients with paroxysmal AF on pre-hospital stage. Materials and methods. An open randomized multicenter prospective study PROMETEI-INSK was conducted. The study included 388 patients with AF paroxysm with mean lasting time of 195 minutes. For the purpose of AF paroxysm treatment amiodarone intravenous bolus was used, in group 2 (268 patients) - propafenone intravenous bolus. The compared groups were matched by sex, age, electrocardiogram (ECG) parameters, and anamnesis of arrhythmic events, comorbid pathology, and therapy. The following investigations were performed: physical examination, medical history taking, ECG before and after rhythm restoration, as well as basic vital factors evaluation (such as heartbeat rate, blood pressure). Study results were processed with the use of statistical data analysis software package Statistica 10 for Windows (StatSoft Inc., USA). Results. AAM effectiveness was evaluated for 24 hours until SR restoration. In the group 1 (amiodarone use) the effectiveness was 61.7% (n=74), in group 2 (propafenone) - 77.6% (n=208); p<0.05. The mean time of rhythm restoration in group 1 was 110 minutes, in group 2 - 22 minutes (p<0.05). Relief of AF paroxysm happened in less than 60 minutes in 25.83% (n=31) of patients in group 1, and in 64.5% (n=173) in group 2; p<0.05. There were no significant differences observed in proarrhythmic and other adverse effects. Conclusion. Propafenone in injectable form is an effective and safe AAM in AF paroxysmal form treatment in comparison with amiodarone on pre-hospital stage. In patients with AF who have no changes in cardiac structure amiodarone is not a first line drug for emergency management of recently emerged AF.

Aim. To demonstrate significance and relevancy of the first angiotensin-converting enzyme inhibitor (ACE inhibitor) captopril use in treatment of patients with cardiovascular disorders. Materials and methods. The article covers the issues of captopril use launch, results of the main randomized clinical studies of it, basic pharmacokinetic characteristics, and indications for captopril use from the perspective of the present clinical guidelines. Conclusion. The first oral ACE inhibitor captopril that was developed more than 40 years ago still holds a valuable place in treatment of cardiovascular diseases such as arterial hypertension, myocardial infarction, congestive heart failure and diabetes mellitus complications. Despite development of ACE inhibitors with longer duration of action and new properties, captopril still remains one of the most effective medications with a wide range of clinical use - from uncomplicated hypertensive crises arrest to long-term use in patients with arterial hypertension, diabetes mellitus, and congestive heart failure. Captopril remains one of the few ACE inhibitors that have changed approaches to treatment of patients with heart failure and improved the survival rate of patients after acute myocardial infarction.

Background. Management of patients with dyspnea syndrome remains complicated in terms of diagnostics and treatment in outpatient conditions. Aim. To present a summary of contemporary view of diagnostic search directions, differential diagnosis in dyspnea syndrome as well as of the main points of therapeutic approach with the focus on diuretics use. Materials and methods. We systematized materials from Russian and foreign publications (PubMed, eLIBRARY and other) for the past 2-15 years as well as present clinical recommendations and guidelines, and provided citations and beliefs of Russian medicine classics about the discussed phenomena in order to write this review. Results. The diagnostic approach in dyspnea syndrome is based in analysis of anamnestic, objective, laboratory and instrumental data and requires from the medical practitioner a scrupulous analytic approach to identify the cause of the disorder and to manage it prescribing pathogenic therapy on time. Diuretics use remains one of the basic approaches to pathogenic therapy. Conclusion. Management of a patient with dyspnea in outpatient conditions remains challenging. It is an interdisciplinary issue that is not completely worked out in terms of diagnostics and treatment and requires fundamental knowledge and awareness of modern approaches to diagnostics and treatment of major disorders characterized with dyspnea syndrome.