Rational pharmacotherapy in cardiology journal. Rational pharmacotherapy of cardiovascular diseases - Chazov E.I. Rational pharmacotherapy in cardiology

Scientific and practical peer-reviewed journal for cardiologists and therapists "Rational Pharmacotherapy in Cardiology" has been published since 2005 with the support of the Russian Society of Cardiology and the State Research Center for Preventive Medicine. It is an all-Russian publication with a frequency of 6 issues per year. Included in the List of publications of the Higher Attestation Commission for the publication of the results of candidate and doctoral dissertations. Distributed by subscription and free of charge at specialized events.

The Editorial Board includes leading Russian scientists in the field of cardiology, preventive cardiology, internal medicine, clinical pharmacology and preventive pharmacotherapy, including 38 doctors of science, including 6 academicians of the Russian Academy of Sciences. The International Editorial Board includes well-known foreign cardiologists.

The main content of the journal is presented by original scientific articles, scientific reviews, lectures, results of the analysis of clinical practice. The journal highlights the problems of early diagnosis, primary and secondary prevention of cardiovascular diseases and comorbidity, effective use drug therapy, topical issues of experimental and clinical pharmacology.

All materials are posted free of charge and undergo a thorough scientific examination: double-blind peer review, plagiarism check, multi-stage editing. Authors are required to provide a declaration of disclosure of conflicts of interest related to the publication. Reviewers are experts in the subject of peer-reviewed materials. In each issue, the best original articles are translated and published in Russian and English.

The journal has a website in Russian (www.rpcardio.ru) and English (www.rpcardio.com) languages, in which full texts of published materials for all years are placed in open access. The journal is also available in the public domain on the website of the Scientific electronic library(NEB) and included in the Russian Science Citation Index (RSCI). In May 2016, the two-year RSCI impact factor for 2015 was 1.051. Full-text electronic versions of all published materials are also available on the websites of the Russian Scientific Electronic Library CyberLeninka and the international open access website DOAJ. Published materials are presented in the electronic databases Web of Science, SCOPUS, EMBASE, Index Copernicus, Ulrich's Periodicals Directory.

Members of the editorial board:

Editor-in-Chief - Boitsov S.A.

Deputy Chief Editors:

Drapkina O.M., Martsevich S.Yu., Oganov R.G., Shalnova S.A.

Lishuta A.S. (Commissioning Editor)

Butina E.K. (executive Secretary)

Editorial board:

Anichkov D.A., Akhmedzhanov N.M., Burtsev V.I. , Vasyuk Yu.A., Gilyarevsky S.R., Gorbunov V.M., Deev D.A., Doshchitsin V.L., Zadionchenko V.S. , Kalinina A.M., Kontsevaya A.V., Kutishenko N.P., Kukharchuk V.V., Lukyanov M.M., Martynov A.I., Napalkov D.A., Nebieridze D.V., Podzolkov V.I., Pozdnyakov Yu.M., Savenkov M.P. , Smirnova M.I., Tkacheva O.N., Chazova I.E. , Shostak N.A., Yakusevich V.V., Yakushin S.S.

Editorial Council:

Adamyan K. G. (Yerevan, Armenia), Vardas P. (Heraklion, Greece), Vijeyraghavan G.

(Thiruvananthapuram, India), Golikov A.P. (Moscow, Russia), DeMaria A. (San Diego, USA),

Dovgalevsky P.Ya. (Samara, Russia), Dzhusipov A.K. (Almaty, Kazakhstan), Zakirova A.N. (Ufa,

Russia), Kenda M.F. (Ljubljana, Slovenia), Kovalenko V.N. (Kyiv, Ukraine), Konradi A.O.

(St. Petersburg, Russia), Kurbanov R. D. (Tashkent, Uzbekistan), Latfullin I. A. (Kazan, Russia) ,

Lopatin Yu.M. (Volgograd, Russia), Matyushin G.V. (Krasnoyarsk, Russia), Mrochek A. G. (Minsk,

Belarus), Nikitin Yu.P., (Novosibirsk, Russia), Oleinikov V.E. (Penza, Russia), Perova N.V.

(Moscow, Russia), Popovich M. I. (Kishinev, Moldova), Pushka P. (Helsinki, Finland),

Stachenko S. (Edmonton, Canada), Fishman B.B. (Veliky Novgorod, Russia),

Tsinamdzgvrishvili B.V. (Tbilisi, Georgia), Shalaev S.V. (Tyumen, Russia).

Year of issue: 2005

Genre: Cardiology

Format: PDF

Quality: eBook (originally computer)

Description: The practical guide "Rational pharmacotherapy of cardiovascular diseases" provides a classification and clinical pharmacology of drugs used in cardiovascular diseases. Typical clinical manifestations, diagnostic criteria, basic principles and treatment regimens for cardiovascular diseases with levels of evidence are described. The features of the management of different groups of patients are highlighted, algorithms for the treatment of individual nosological forms are given. The guide contains a wide range of reference Information facilitating a rational individualized choice of drug and treatment regimen.
The practical guide "Rational pharmacotherapy of cardiovascular diseases" is intended for practicing physicians, students of higher medical educational institutions and students of refresher courses.

Clinical pharmacology of drugs for the treatment of cardiovascular diseases
Beta blockers
calcium antagonists (blockers) calcium channels)
Angiotensin-converting enzyme inhibitors
Angiotensin II receptor blockers
Centrally acting antihypertensives
Central a2 receptor agonists
Imidazoline 1-receptor agonists
Direct acting vasodilators (myotropic)
Alpha blockers
Ganglioblockers
Diuretics
Loop (potent) diuretics
Thiazide and thiazide-like diuretics
Carbonic anhydrase inhibitors
Potassium sparing diuretics
Aldosterone receptor antagonists
Nitrates
cardiac glycosides
Adrenomimetics
Antiarrhythmic drugs
Drugs affecting blood coagulation and platelet function
Direct acting anticoagulants
Unfractionated (standard) heparin
Low molecular weight (fractionated) heparins
Fondaparinux sodium
Direct acting thrombin inhibitors
Indirect anticoagulants
Antiplatelet agents
Acetylsalicylic acid
Thienopyridine derivatives
Blockers of glycoprotein IIb/IIIa platelet receptors
fibrinolytics
Lipid-lowering drugs
HMG-CoA reductase inhibitors (statins)
Fibric acid derivatives (fibrates)
Nicotinic acid and its derivatives
Bile acid sequestrants
Non-steroidal anti-inflammatory drugs
Narcotic analgesics
Phlebotonizing agents
Clinical guidelines
Chronic ischemic heart disease
Unstable angina
myocardial infarction
Atherosclerosis. Lipid metabolism disorders
arterial hypertension. Hypertonic disease
Secondary (symptomatic) arterial hypertension
hypertension due to kidney disease
AG in glomerulonephritis and pyelonephritis
hypertension in diabetic nephropathy
Vasorenal hypertension
Hypertension due to diseases of the cardiovascular system
AH in coarctation of the aorta
AH in nonspecific aortoarteritis
Hypertension due to diseases of the endocrine system
Hypertension in hypersecretion of mineralocorticoids
Hypertension in hypersecretion of glucocorticoids (syndrome and Itsenko-Cushing's disease)
AH in pheochromocytoma
hypertension in hypothyroidism
metabolic syndrome
Pulmonary hypertension
Heart rhythm disorders
Changes in automatism of the sinoatrial node
sinus arrhythmia
Sinus bradycardia
Sinus tachycardia
Sick sinus syndrome
Ectopic beats and rhythms
Passive (substituting or slipping) complexes and rhythms
Active ectopic impulses (complexes) and rhythms. Extrasystole Supraventricular tachycardia
Automatic atrial tachycardia
Reciprocal tachycardias
Reciprocal AV nodal tachycardia
atrial flutter
Atrial fibrillation (atrial fibrillation)
Ventricular tachycardia
Flutter and ventricular fibrillation
WPW syndrome
Thromboembolic complications in patients with atrial fibrillation
Heart failure
Cardiomyopathy
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy
Myocarditis
Diseases of the pericardium
Pericarditis
Cardiac tamponade
Constrictive pericarditis
Infective endocarditis
Acute rheumatic fever and rheumatic heart disease
Systemic vasculitis
Polyarteritis nodosa
Microscopic polyangiitis
Wegener's granulomatosis
Churg-Strauss syndrome (allergic angiitis and granulomatosis)
Hemorrhagic vasculitis (Schonlein-Henoch purpura)
Giant cell arteritis and polymyalgia rheumatica
Arteritis Takayasu (nonspecific aortoarteritis)
Essential cryoglobulinemic vasculitis
Deep vein thrombosis and pulmonary embolism
Chronic venous insufficiency of the lower extremities
Descriptions of medicines
Aymalin
Acridilol
Acripamide
Aksetin
Actovegin
Amiodarone
Amlodipine
Amphetamine
Aponil
Aspirin cardio
Atenolol
Atorvastatin
Acenocoumarol
Acetazolamide
Bezafibrate
Bendazol
Betak
Betaxolol
Bisogamma
bisoprolol
Bretylium tosylate
bumecain
Warfarin Nycomed
Verapamil
Veroshpiron
Vincamine
Gallopamil
Gemfibrozil
Heparin sodium
Heparinoid
Hydralazine
Hydrochlorothiazide
Glukobay
Glucophage
Dalteparin sodium
Detralex
diazem
Diakarb
Digitoxin
Digoxin
Diltiazem
Dipyridamole
Diroton
Doxazosin
Isoprenaline
Isosorbide dinitrate
Isosorbide mononitrate
Invoril
Indapamide
Indapamide
Indobufen
Ionic
Irbesartan
Iruzid
Irumed
Candesartan
Kapoten
Captopril
Carvedilol
Cardiomagnyl
Clexane
clerimed
Clonidine
Clopamid
Concor
Concor Core
Xanthinol nicotinate
Lanatoside C
Lappaconitine hydrobromide
Lacidipine
Lisinopril
Lovastatin
Losartan
Medakson
Medoklav
Medostatin
Melox
Methyldopa
Metocard
metoprolol
Mildronate
Minoxidil
Moxonidine
molsidomine
Moexipril
Nadolol
Nadroparin calcium
Nebivolol
non-ticket
Nicardipine
A nicotinic acid
Nimodipine
Nitrendipine
Nitroglycerine
Nitrocore spray
Nifedipine
Nifecard HL
Nicergoline
Normodipin
Oxprenolol
Omelar Cardio
Osmo-Adalat
Perindopril
Pindolol
Pravastatin
Prazosin
Primalium bitartrate
Preductal MV
Prestarium
Procainamide
propafenone
propranolol
Proroxan
Purolase
Ramipril
Renipril
Renipril GT
Rilmenidine
Riodipine
Selemycin
Simvastatin
Simvor
HoneycombGEXAL
Spirapril
Talinolol
Telmisartan
Terazosin
Ticlopidin
Tinzaparin sodium
Trandolapril
Triamterene
Trimetazidine
Trinitrolong
ouabain
Urapidil
Urokinase
Felodipine
phenindione
Phenytoin
Fenofibrate
Phentolamine
fluvastatin
Flunarizine
Fosinopril
Quinapril
Quinidine
Chlortalidone
Celiprolol
Cilazapril
Cinnarizine
Ciprofibrate
Ednit
Enalapril
EnalaprilGEKSAL
Enalaprilat
Enam
Enarenal
Enoxaparin sodium
Eprosartan
Eptifibatide
Esmolol
Ethyl biscumacetate
LITERATURE

For citation: Maksimov M.L. Rational pharmacotherapy of coronary heart disease: b-blockers and calcium antagonists in the treatment of stable angina // BC. 2014. No. 2. S. 124

According to official statistics, the first line in the structure of causes of death in Russia is invariably occupied by mortality from diseases of the circulatory system, which account for more than 55% of the total number of deaths in the country. Diseases of the circulatory system in the first half of 2013 alone caused the death of 525,431 people. Ischemic disease heart disease (IHD) and cerebrovascular diseases are the leading causes of death in Russia. They account for 29.1% and 16.9% of deaths from all causes, respectively. The frequency of angina pectoris increases sharply with age: in women from 0.1-1% at the age of 45-54 years to 10-15% at the age of 65-74 years; in men from 2-5% at the age of 45-54 to 10-20% at the age of 65-74. Most European countries the prevalence of angina pectoris is 20-40 thousand per 1 million population. This explains the great interest of practitioners in the proper management of patients with angina pectoris and the choice of optimal treatment methods. The high mortality that exists in Russia can be reduced with a decisive transition of each doctor from the tactics of symptomatic treatment to a strategy of comprehensive and systematic secondary prevention.

The main pathophysiological mechanism of coronary artery disease is a discrepancy between myocardial oxygen demand and the ability of coronary blood flow to satisfy them. Atherosclerosis and dynamic obstruction contribute to the development of this discrepancy. coronary arteries due to their spasm, violation of the mechanisms of expansion of the coronary vessels (insufficiency of local vasodilating factors against the background of high myocardial oxygen demand, an unusually large increase in myocardial oxygen demand under the influence of intense physical activity, emotional stress, leading to the release of catecholamines into the blood, the excess level of which has cardiotoxic effect).

In the treatment of angina pectoris, two main goals are defined: to improve prognosis, prevent the occurrence of myocardial infarction and sudden death and increase life expectancy, as well as reduce the frequency and intensity of angina attacks and improve the patient's quality of life. To achieve these goals, in addition to non-drug treatment, reducing modifying risk factors, educating patients, it is necessary to prescribe rational daily pharmacotherapy with individual selection and correction of drugs according to clinical, instrumental and laboratory research data. It is advisable for patients to avoid exertion that causes angina pectoris and take nitroglycerin under the tongue to relieve it. It is also important to adequately treat concomitant diseases: arterial hypertension (AH), diabetes mellitus, hypo- and hyperthyroidism, etc. In patients with IHD, the level of blood pressure should be reduced to the target value of 130/85 mm Hg. Art. In patients diabetes and/or kidney disease, target BP should be less than 130/85 mm Hg. Art. Conditions such as anemia, hyperthyroidism require special attention. lifestyle modification, medicines and revascularization help to minimize symptoms or completely eliminate angina, although not all of these approaches may be necessary for a particular patient.

1. Drugs that improve prognosis in patients with angina pectoris

Acetylsalicylic acid (ASA) 75-150 mg/day in all patients in the absence of contraindications (active gastrointestinal bleeding, ASA allergy or intolerance) (A).

Statins in all patients with coronary heart disease (A).

Oral beta-blockers in patients with a history of myocardial infarction or heart failure (A).

ACE inhibitors or ARBs in the presence of hypertension, heart failure, left ventricular dysfunction, prior myocardial infarction with left ventricular dysfunction, or diabetes mellitus (A).

Class II a

ACE inhibitors or ARBs in all patients with angina and confirmed coronary heart disease (B).

Clopidogrel as an alternative to ASA in patients with stable angina who cannot take ASA, for example due to allergies (B).

High-dose statins, if present high risk(cardiovascular mortality over 2% per year) in patients with proven coronary heart disease (B).

Fibrates for low HDL or high triglycerides in patients with diabetes mellitus or metabolic syndrome (B).

2. Drug therapy aimed at relieving symptoms

Short-acting nitroglycerin for angina relief and situational prophylaxis (patients should receive adequate instructions for the use of nitroglycerin) (B).

Evaluate the effectiveness of b1-blocker and titrate its dose to the maximum therapeutic; evaluate the feasibility of using a long-acting drug (A).

In case of poor tolerance or low efficacy of a b-blocker, prescribe monotherapy with BMCC (A), long-acting nitrate (C).

If monotherapy with a b-blocker is not effective enough, add dihydropyridine BMCC (B).

Class II a

In case of poor tolerance of a b-blocker, prescribe an inhibitor of If-channels of the sinus node - ivabradine (B).

If monotherapy with CBCC or combination therapy with CBCC and a β-blocker is ineffective, replace CBCC with long-acting nitrate. Avoid development of nitrate tolerance (C).

⎯Metabolic drugs (trimetazidine MB) can be used in addition to standard drugs or as an alternative to them in case of poor tolerance (B) .

Beta-blockers (BABs) are drugs that selectively block β-adrenergic receptors and eliminate the effects of adrenaline on effector organs mediated through β-adrenergic receptors.

Beta-blockers represent a group of drugs that is very heterogeneous in terms of their pharmacological effects, the only common property of which is competitive antagonism against β1-adrenergic receptors. Along with the blockade of β1-adrenergic receptors, β-blockers can block β2-adrenergic receptors. In the first case, they talk about non-selective BBs, in the second - about β1-selective drugs. BABs also differ in the presence or absence of internal sympathomimetic activity (ISA), vasodilating action, and lipophilicity. The drugs of this group competitively displace adrenaline from its connection with β-adrenergic receptors on the effector organ.

BABs that selectively act on the heart (selective) are distinguished by a higher affinity for myocardial β1-adrenoreceptors than for β2-adrenergic receptors of blood vessels and bronchi (mainly in therapeutic doses). Non-selective BBs act on both β1 and β2-adrenergic receptors. BABs have hypotensive, antianginal, antiarrhythmic, negative foreign-, chrono-, dromo- and bathmotropic effects. By inhibiting β-adrenergic receptors of the heart, 75% of which are β1 and 25% - β2 receptors, they reduce the formation of cAMP from ATP stimulated by catecholamines, and reduce the intracellular current of calcium ions. This leads to a decrease in heart rate, inhibition of conduction and a decrease in myocardial contractility.

The antianginal effect of BAB is due to a decrease in myocardial oxygen demand as a result of a decrease in heart rate (diastole lengthens and myocardial perfusion improves) and a decrease in contractility, as well as a narrowing of the coronary vessels of non-ischemic areas, which leads to redistribution of blood to the zones of ischemic areas of the myocardium. The mechanism of the hypotensive action of BAB is the inhibition of presynaptic β2 receptors, in connection with which the release of noradrenaline into the synaptic cleft decreases, and, consequently, the stimulation of α receptors blood vessels, a decrease in the activity of the renin-angiotensin-aldosterone system (blockade of β1 receptors of the juxtaglomerular cells of the kidneys), inhibition of the vasomotor center (for drugs that penetrate the central nervous system), restoration of the baroreceptor mechanism (due to a decrease in cardiac output).

The antiarrhythmic effect of BAB is determined by the inhibitory effect on factors such as an increase in the activity of the sympathetic nervous system and cAMP, which plays an important role in the occurrence of ventricular fibrillation in myocardial ischemia and increased blood pressure. BAB inhibit impulse conduction in the antegrade and, to a lesser extent, in the retrograde directions through the AV node and along additional pathways. Most selective β-blockers in therapeutic doses do not have a cardiodepressive effect, do not affect glucose metabolism and do not cause retention of sodium ions in the body. Selective β-blockers affect insulin release and carbohydrate metabolism to a lesser extent than non-selective ones, mask the symptoms of hypoglycemia in patients with diabetes mellitus, increase triglycerides, reduce free fatty acids and high-density lipoproteins. When used in therapeutic doses, selective BBs have less pronounced influence on the smooth muscles of the bronchi and peripheral arteries and on lipid metabolism than non-selective ones.

BBs are first-line drugs (A) in patients with angina attacks, who have had a myocardial infarction, or when diagnosing episodes of myocardial ischemia in patients using instrumental methods. Due to the decrease in adrenergic activation of the heart, β-blockers increase exercise tolerance and reduce the frequency and intensity of angina attacks, resulting in an improvement in symptoms, and reduce myocardial oxygen demand. In addition, they increase the delivery of oxygen to the myocardium (due to increased collateral blood flow and its redistribution in favor of the ischemic layers of the myocardium - the subendocardium). The choice of drug for angina pectoris depends on the clinical situation and the patient's individual response.

In the pharmacotherapy of patients with coronary artery disease, preference should be given to selective long-acting BBs, without ICA. These medications much less frequently than non-selective BBs, they cause side effects of therapy and therefore can be used in patients with coronary artery disease with a tendency to bronchospasm, patients with COPD, with metabolic syndrome, diabetes mellitus and with peripheral circulatory disorders. Their effectiveness has been proven in large clinical trials. Such data were obtained using sustained release metoprolol, bisoprolol, nebivolol and carvedilol. Therefore, these BABs are recommended for patients who have had AMI. When prescribing alprenolol, atenolol, oxprenolol positive results failed to receive. A meta-analysis of 82 randomized trials showed that long-term use of β-blockers leads to an additional reduction in the risk of death and the development of recurrent MI in patients who have had MI and who took ASA, fibrinolytics, and ACE inhibitors.

Data from large prospective studies suggest that long-term use of β-blockers increases the survival rate of patients with MI by 25% due to a significant reduction in the number of deaths from cardiovascular diseases, including sudden death and recurrent MI. In patients with coronary artery disease, the most pronounced cardioprotective effect is exerted by lipophilic drugs (reducing mortality by an average of 30%) - betaxolol, carvedilol, metoprolol, propranolol, timolol, etc. and BAB without ICA (by an average of 28%): metoprolol, propranolol and timolol. At the same time, neither BAB with ICA (alprenolol, oxprenolol and pindolol), nor hydrophilic drugs (atenolol and sotalol) prevent death in this category of patients with long-term use. Bisoprolol is a highly selective β1-adrenergic blocker, without ICA, successfully combines the advantages of lipo- and hydrophilic β-blockers, a long half-life and a small number of side effects.

Bisoprolol has a dual route of elimination - metabolism in the liver and filtration in the kidneys (balanced clearance), which makes it possible to use it in case of impaired liver or kidney function. However, in severe renal / hepatic insufficiency, the dose is recommended to be reduced by 2 times. It binds to plasma proteins by 30%, therefore, interaction with other drugs at the level of protein binding is excluded. Metabolized by 40-60%. The main metabolic pathway is CYP2D6 oxidation, which is characterized by genetic polymorphism. However, unlike propranolol, metoprolol, carvedilol, nebivolol, the pharmacokinetics of bisoprolol does not depend on the genetic polymorphism of CYP2D6, thus, its pharmacokinetics does not depend on the genetic characteristics of the patient. Bisoprolol can be used in patients with COPD, provided adequate concomitant bronchodilator therapy under careful monitoring of the clinical condition of patients and respiratory function parameters.

As real clinical practice shows, drugs with different trade names, based on the same active substance, can differ significantly in therapeutic efficacy. The study "Comparison of the clinical efficacy of the original drug bisoprolol and its generic drug in patients with stable angina in combination with chronic obstructive pulmonary disease" showed that only when prescribing the original drug bisoprolol (Concor, Takeda Pharmaceuticals LLC) the target heart rate range and improvement in endothelial function are achieved, which allows to realize long-term cardiovascular effects and talk about its greater clinical efficacy. The generic drug had no effect on endothelial function: there were no significant changes in EDVD, as well as serum concentrations of nitric oxide metabolites. It was noted that in patients with coronary artery disease with concomitant COPD, only the original bisoprolol is able to improve the functional state of the endothelium. Initially, in all patients in the study, N.Yu. Grigorieva et al. there were violations of bronchial patency. After 12 weeks in patients taking the original drug, the parameters of respiratory function did not change, which is due to the proven high cardioselectivity (1:75) of bisoprolol. In the surveyed, taking a generic drug, after 4 weeks. treatment, there was no significant dynamics in the parameters of respiratory function, however, after 12 weeks. a statistically significant decrease in respiratory function was registered. The deterioration of bronchial patency when taking generic bisoprolol is most likely due to the quality of its main molecule and the excipients contained in it, which could affect bronchial patency. Thus, in order to prevent the development of bronchial obstruction, patients with coronary artery disease with concomitant COPD should be prescribed the original bisoprolol.

The data of the conducted studies showed that the use of bisoprolol not only reduces the severity of clinical symptoms, but also significantly improves the prognosis. In patients with stable angina, the number and duration of transient episodes of ischemia can be significantly reduced, there is a decrease in mortality, incidence of coronary artery disease and improvement general condition sick. Bisoprolol promotes exercise tolerance to a greater extent than atenolol and metoprolol, it causes a significant increase in exercise capacity and a dose-dependent effect on exercise tolerance. It has been shown that bisoprolol, to a much greater extent than atenolol and metoprolol, improves the quality of life of patients and reduces anxiety and fatigue. Very importantly, bisoprolol reduces cardiovascular mortality and the risk of fatal MI in high-risk patients undergoing cardiac surgery.

So, in a double-blind study by L. van de Ven et al. demonstrated that in stable angina pectoris, the efficacy of bisoprolol at a dose of 10 mg 1 r./day is significantly higher than that of isosorbide dinitrate at a dose of 20 mg 3 r./day.

In a multicenter controlled study TIBBS (Total Ischemic Burden Bisoprolol Study) compared the effect of bisoprolol (Concor) and prolonged nifedipine on transient myocardial ischemia in patients with stable angina pectoris. This study included 330 patients who had had at least 3 episodes of myocardial ischemia within 48 hours before randomization according to Holter monitoring of the electrocardiogram. Therapy with bisoprolol (Concor) was received by 161 patients, 169 by sustained release nifedipine. All patients received placebo for 10 days, then for 4 weeks. - bisoprolol at a dose of 10 mg / day or retarded nifedipine at a dose of 20 mg 2 times a day. In the next 4 weeks. patients received double doses of the same drugs. At the end of the study, the mean number of episodes of myocardial ischemia was statistically significantly lower in the Concor group. In addition, the number of ischemic episodes in the early morning hours significantly decreased in this group. Bisoprolol was more effective than extended-release nifedipine in terms of the duration of ischemic episodes (bisoprolol - 68%, versus nifedipine - 28%), the severity of ischemic attacks (-70% on bisoprolol and -40% on nifedipine), the number of ischemic episodes (-60% on bisoprolol versus 29% on nifedipine). It is also important that the TIBBS study showed a direct correlation between the number and duration of episodes of myocardial ischemia with the frequency of deaths, fatal cardiovascular events and myocardial revascularization operations. Thus, Concor, eliminating episodes of myocardial ischemia, has a positive effect on the prognosis in stable angina pectoris.

Another important class of drugs used in the complex pharmacotherapy of coronary artery disease, today certainly recognize slow calcium channel blockers (CCB) or (in the terminology of other sources) calcium antagonists. The ability of BMCC to relax the smooth muscles of the walls of muscle-type arteries, arterioles and, thus, reduce the total peripheral vascular resistance (TPVR) served as the basis for the widespread use of these drugs in hypertension and coronary artery disease. Slow calcium channel blockers have a vasodilating effect, and the most powerful vasodilators are drugs from the group of dihydropyridines. In vasospastic angina (variant angina, Prinzmetal's angina), BMCCs, dihydropyridine derivatives, are used to prevent attacks. Dihydropyridines, to a greater extent than other BMCCs, eliminate spasm of the coronary arteries and therefore are the drugs of choice for vasospastic angina pectoris. The mechanism of antianginal and hypotensive action is due to their ability to cause expansion of peripheral and coronary arteries, therefore, these drugs can be considered as an addition, and sometimes as an alternative to nitrates, which also have a vasodilatory effect.

Prescription of short-acting dihydropyridine derivatives should be avoided, since they can worsen the symptoms and prognosis of life in IHD. Powerful vasodilation caused by nifedipine leads to stimulation of the sympathoadrenal system with the development of hypercatecholaminemia, causing tachycardia, facial flushing, and arrhythmogenic effect. In addition, coronary dilatation can cause steal syndrome. According to current recommendations, patients with coronary artery disease should be prescribed only prolonged dihydropyridine BMCC II and III generation, used 1 r./day, especially in the combination of coronary artery disease and hypertension. Amlodipine should be considered the drug of first choice, which has a sufficient evidence base in multicenter clinical trials. Amlodipine causes expansion of large-caliber coronary arteries, as well as coronary arterioles, both intact and ischemic areas of the myocardium. This ensures the supply of oxygen to myocardial cells during spasms of the coronary arteries. In addition, by expanding the peripheral arterioles, amlodipine reduces OPSS, while reflex tachycardia, as a rule, does not develop. The efficacy of amlodipine in patients with angina pectoris is higher than that of diltiazem.

Summarizing the above, we can note the relevance of the appearance on the Russian pharmaceutical market of the combination of the most widely used calcium antagonist (amlodipine) with the most widely used β-adrenergic blocker (bisoprolol) as part of one tablet, administered 1 r./day - Concor AM (LLC "Takeda Pharmaceuticals" ). This combination is a rational hypotensive and anti-ischemic. Complementary effects due to different mechanisms of action: amlodipine reduces central aortic pressure and peripheral vascular resistance, and bisoprolol - left ventricular stroke volume and renin secretion, which prevents vasoconstriction. The drugs weaken the reflex reactions associated with taking another component of the combination: bisoprolol prevents negative effect reflex activation of the SNS caused by taking amlodipine, and amlodipine - reflex vasoconstriction caused by the action of bisoprolol.

It is also worth noting the similar pharmacokinetic parameters of the two drugs: a long half-life, action for 24 hours. So, in a study by R. Rana et al. in 801 patients with newly diagnosed essential hypertension stage 2 within 4 weeks. treatment with Concor AM (5 mg bisoprolol + 5 mg amlodipine), target blood pressure values ​​(<140 и <90 мм рт. ст. для САД и ДАД соответственно) были достигнуты у 82,5% пациентов. Помимо предсказуемой гипотензивной эффективности комбинации было показано отчетливое снижение ЧСС на 10,4%. За 4 нед. терапии средняя ЧСС снизилась с исходного среднего 83,3 уд./ мин. до 74,6 уд./мин. При этом отмечена хорошая переносимость комбинации, низкая частота нежелательных лекарственных реакций. Исследователи отметили отличную или хорошую эффективность препарата у 91,4% пациентов, а 90,6% больных - отличную или хорошую его переносимость . Это важно, поскольку повышенная ЧСС является одним из значимых факторов риска сердечно-сосудистого заболевания. Обоснованием применимости комбинации бисопролола и амлодипина в лечении пациентов с ИБС можно считать: высокую эффективность и безопасность обоих препаратов, особенно при сочетании ИБС и АГ .

Thus, β-blockers in the world and Russian medical practice today are widely used in the treatment and prevention of cardiovascular diseases and their complications. They are recognized as first-line drugs in most international and national guidelines for the treatment of coronary artery disease and hypertension. Bisoprolol and other highly selective β-blockers without ICA are recommended as the main therapy for all forms of coronary artery disease, including patients with acute coronary syndrome and AMI. The drugs in this group are the first choice for the treatment of patients with angina, especially patients who have had myocardial infarction, because they lead to a proven reduction in mortality and the incidence of recurrent myocardial infarction. If BAB monotherapy is insufficient, then nitrates or calcium antagonists from the group of dihydropyridines are added to the treatment.

The combination of bisoprolol in combination with amlodipine (Concor AM) is a rational antihypertensive combination, which, given the decrease in heart rate and myocardial load, can be successfully used in the treatment of coronary artery disease, stable angina, especially in combination with hypertension. The presence of 4 different dose variants of the composition of the drug Concor AM (bisoprolol / amlodipine 5 mg / 5 mg, 5 mg / 10 mg, 10 mg / 5 mg, 10 mg / 10 mg) determines the convenience for the doctor and patient in selecting an adequate dose of the combined drug. Bisoprolol in combination with amlodipine (Concor AM) can be considered an indispensable drug in the treatment of coronary artery disease, especially with poor nitrate tolerance.

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