Comparative analysis of the effectiveness and safety of various dosage forms of metoprolol in the treatment of cardiovascular diseases

Pharmacodynamics and pharmacokinetics

The drug has antiarrhythmic, antianginal and hypotensive effects. The drug does not have internal SMA and does not have a membrane-stabilizing effect.

The hypotensive effect is due to a decrease in the synthesis of renin, monooxygenase, inhibition of the activity of the renin-angiotensin system and the central nervous system. The drug can lower blood pressure during stress and physical exertion at rest.

The antianginal effect is ensured by a decrease in pulse rate, as well as a decrease in the need for oxygen in myocardial tissue. Long-term use of the medication increases exercise tolerance and reduces the severity of angina attacks and their frequency. As a result of eliminating arrhythmogenic factors (arterial hypertension, increased cAMP content, tachycardia, increased activity of the sympathetic nervous system), an antiarrhythmic effect is achieved.

For thyrotoxicosis, heart diseases of functional origin, sinus tachycardia , atrial fibrillation, supraventricular tachycardia, Metoprolol allows you to restore sinus rhythm and reduce heart rate. The drug prevents the formation of migraines.

Average therapeutic dosages of metoprolol, unlike other beta-blockers, have a less pronounced effect on the organs in which beta-2-blockers are located (uterus, bronchi, smooth muscle tissue of peripheral arteries, skeletal muscles, pancreas) and on carbohydrate metabolism.

Long-term use of the medication leads to a decrease in blood cholesterol levels.

pharmachologic effect

Manufacturer: Ozone (Russia)
Release form: tablets

Active ingredient: metoprolol

Analogs: Bisoprolol, Anaprilin, Betalok zok

Metoprolol belongs to the group of selective beta-blockers. Based on the chemical composition, there are 2 forms of the drug: Metoprolol tartrate and Metoprolol succinate. The medication reduces the frequency and severity of angina attacks, lowers blood pressure and restores the rhythm of heart contractions.

Under the influence of the drug, the need for oxygen in the cellular structures of the myocardium decreases, and the tolerance of the heart muscle to physical activity increases.

Indications for use of Metoprolol

The medicine is used for myocardial infarction , unstable angina , exertional angina , coronary , arterial hypertension arterial hypertension crisis .

The drug is used for rhythm disturbances: supraventricular arrhythmia , ventricular form of arrhythmia, sinus tachycardia , atrial tachycardia, atrial flutter, atrial fibrillation , ventricular extrasystole .

The drug is used for thyrotoxicosis (in complex therapy), for tremor (senile, essential forms), for migraines, withdrawal syndrome , akathisia when taking antipsychotics, and for anxiety.

Release form of Metoprolol

Metoprolol is available in tablet form for systemic treatment. The main substance is metoprolol tartrate, which can be contained in the amount of 25 mg, 50 mg or 100 mg in one tablet. Auxiliary components:

• magnesium stearate;
• silica;
• sodium carboxymethyl starch;
• microcrystalline cellulose.

The drug belongs to the cardioselective beta-blockers.

Contraindications

Metoprolol is not prescribed for 2-3 degree atrioventricular block, cardiogenic shock , intolerance to the active substance, acute form of heart failure , and arterial hypotension , Prinzmetal's angina , breastfeeding, in the acute period of myocardial infarction, simultaneous use of an MAO inhibitor, with intravenous infusion of Verapamil.

With metabolic acidosis , myasthenia gravis, diabetes mellitus, liver failure, pheochromocytoma, chronic renal failure, COPD (chronic obstructive bronchitis , emphysema ), with bronchial asthma, obliterating disease of peripheral vessels, during pregnancy, thyrotoxicosis, psoriasis, depression, in pediatric practice, persons In elderly patients, the medicine is prescribed with caution.

Metoprolol or Concor - which is better for arrhythmia

Manufacturer: Merck KGaA (Germany)
Release form: tablets

Active ingredient: bisoprolol

Metoprolol and its analog Concor have the same indications, but a different mechanism of action due to different active components. Medicines are used for chronic heart failure, arterial hypertension, coronary heart disease complicated by angina pectoris.

For arrhythmia, the best substitute for Metoprolol is Concor, since the drug is fast-acting. The patient's condition improves within half an hour from taking the medicine.

Side effects

Nervous system: slower speed of motor and mental reactions, weakness, headaches, increased fatigue, paresthesia in the extremities, convulsions, tremors, drowsiness, attention disorders, anxiety, insomnia, myasthenia gravis, hallucinations, memory impairment, confusion, “nightmare” dreams, asthenia.

Sense organs: eye pain, decreased vision, conjunctivitis, dry eyes, decreased tear production.

Cardiovascular system: orthostatic hypotension , loss of consciousness, dizziness, drop in blood pressure, sinus bradycardia, swelling, decreased myocardial contractility, cardialgia , myocardial conduction disorders, manifestation of vasospasm, CHF, rarely worsening of impaired atrioventricular conduction is observed.

Digestive tract: changes in taste, disturbances in liver function (cholestasis, darkening of urine, yellowing of the skin and sclera).

Skin: photodermatosis , psoriasis-like skin reactions, exacerbation of psoriasis, skin rashes, exanthema, reversible form of alopecia, increased sweating.

Respiratory system: bronchospasm, nasal congestion, shortness of breath.

Endocrine system: hypoglycemia (in insulin-requiring diabetes mellitus), hyperglycemia (in persons with non-insulin-dependent diabetes mellitus), hypothyroid state. Possible development of rash, itching, allergies, thrombocytopenia, hyperbilirubinemia, agranulocytosis.

The effect of Metoprolol on the fetus: hypoglycemia, intrauterine growth retardation, bradycardia.

The drug can cause decreased potency, libido, weight gain, and joint pain. Abrupt cessation of taking the drug causes the development of “withdrawal syndrome”.

Side effects of Metoprolol

Taking Metoprolol in rare cases can cause a number of side effects:

• increased fatigue;
• drowsiness;
• decreased concentration;
• sleep disorders.

Less common are negative effects on the organ of vision: dry tear duct, dry eye syndrome and pain.

From the digestive tract - taste disturbance and decreased liver function. In addition, skin reactions in the form of photodermatosis also occur. If the patient has a manifestation of psoriasis on the skin, the affected area may increase or enter an acute stage. In some patients, the intensity of sweating increases.

From the respiratory system - nasal congestion, bronchospasm or shortness of breath appears.

Metoprolol tablets, instructions for use (Method and dosage)

The medicine is taken orally. Tablets should not be divided in half, chewed, or broken. The average dosage for arterial hypertension is 100-150 mg for 1-2 doses per day.

Angina: 2-3 times a day 50 mg.

Thyrotoxicosis, hyperkinetic cardiac syndrome, tachyarrhythmia: 1-2 times a day, 50 mg.

For secondary prevention of myocardial infarction, 200 mg of metoprolol is indicated.

For the prevention of migraine, 100-200 mg per day is prescribed for 2-4 doses.

In case of paroxysmal supraventricular tachycardia, in order to stop the attack, it is administered parenterally under inpatient observation.

In case of acute myocardial infarction, Metoprolol is administered immediately after hospitalization of the patient; it is necessary to monitor the level of blood pressure, pulse, ECG, and atrioventricular conduction.

For elderly people, therapy begins with 50 mg per day. In case of pathology of the hepatic system, dosage adjustment is not carried out (it is preferable to prescribe drugs that are not metabolized in the hepatic system).

Instructions for use of Metoprolol Ratiopharm and Metoprolol Acri are similar.

Metoprolol or Bisoprolol - which is better for arrhythmia and tachycardia, what is the difference

Manufacturer: VERTEX (Russia)
Release form: tablets

Active ingredient: bisoprolol

Metoprolol and Bisoprolol belong to the same pharmacological group, have equivalent indications for use, but have a different mechanism of action, which is due to different active substances.

The action of Bisoprolol is aimed at reducing the symptoms of myocardial ischemia, normalizing blood pressure and restoring the heart rate. Despite the similarity of medications, there are differences between them:

• Metoprolol begins to act within half an hour after taking the drug, and Bisoprolol - 1–1.5 hours after its use;
• the duration of activity of the Bisoprolol analogue reaches 12 hours, so the drug is taken once a day, while for Metoprolol it lasts only up to 4 hours and is taken several times a day;
• Metoprolol is excreted from the body only through the liver, which creates additional stress on the organ, and Bisoprolol is removed through the kidneys and liver.

According to doctors, Bisoprolol is well tolerated and is more often prescribed for arrhythmia or tachycardia, since it effectively copes with this cardiac pathology and is convenient to take once a day.

Overdose

Manifested by dizziness, drop in blood pressure, sinus bradycardia , arrhythmias, fainting, ventricular extrasystole , cardiogenic shock, heart failure, cardiac arrest, bronchospasm , nausea, vomiting, coma, loss of consciousness.

The first symptoms are observed 20 minutes after taking increased doses of the drug.

The administration of enterosorbents and timely gastric lavage are required. If there is a significant drop in blood pressure, the patient is placed in a Trendelenburg position and norepinephrine, Dobutamine , and Dopamine . Later glucagon , and an intracardial pacemaker is installed in a transvenous manner as needed.

Diazepam is administered slowly intravenously . When bronchospasm develops, beta-2 adrenergic stimulants are administered intravenously.

Hemodialysis has not proven effective.

Nebivolol

Manufacturer: Salutas Pharma GmbH (Germany)
Release form: tablets

Active ingredient: nebivolol

Nebivolol belongs to the group of beta-blockers and is a racemate consisting of 2 enantiomers - L-Nebivolol and D-Nebivolol. The drug reduces blood pressure and pulse with a single dose. A stable hypotensive effect is observed 1–2 weeks after regular use of the drug.

Nebivolol is prescribed 2.5-5 mg 1 time in 1 half day. According to indications, the dosage of the medicine can be increased to 10 mg per day.

Interaction

Extracts of allergens used for skin testing, the allergens themselves significantly increase the likelihood of developing anaphylaxis, severe systemic allergic reactions in patients who use Metoprolol.

The risk of developing anaphylactic reactions increases with intravenous administration of radiocontrast drugs based on iodine . Medicines for general inhalation anesthesia, phenytoin when administered intravenously increase the likelihood of a drop in blood pressure and increase the severity of the cardiodepressive effect.

Metoprolol can mask the symptoms of hypoglycemia (high blood pressure, tachycardia ) and change the effectiveness of oral forms of hypoglycemic agents, insulin.

The drug reduces the clearance of xanthines, lidocaine , increasing their concentration in the blood plasma, especially in patients with increased clearance of theophylline with concomitant smoking.

Estrogens, glucocorticosteroids, NSAIDs weaken the hypotensive effect of the drug.

Methyldopa , Reserpine , BMCC, cardiac glycosides, antiarrhythmic drugs, Amiodarone , Diltiazem , Verapamil , guanfacine - aggravate the course of bradycardia , heart failure , atrioventricular block .

When taking Nifedipine, a significant drop in blood pressure is observed. Hydralazine , sympatholytics, clonidine , diuretics, and other antihypertensive drugs can provoke a sharp and excessive drop in blood pressure.

Metoprolol prolongs the period of anticoagulant action of coumarins and increases the period of action of non-depolarizing muscle relaxants. Antipsychotic drugs, tetracyclic antidepressants, neuroleptics, tricyclic antidepressants, hypnotics and sedatives, ethanol - enhance the inhibitory effect of metoprolol on the central nervous system.

The simultaneous administration of MAO inhibitors is unacceptable due to the risk of a sharp drop in blood pressure.

Impaired peripheral circulation is observed when non-hydrogenated ergot alkaloids are prescribed.

Metoprolol or Anaprilin - which is better?

Manufacturer: Sintez OJSC (Russia)
Release form: tablets

Active ingredient: propranolol

Anaprilin and Metoprolol are beta-blockers, the active substances of which are:

• reduce heart rate;
• reduce myocardial oxygen demand;
• reduce blood pressure;
• effectively reduce attacks of angina in coronary heart disease;
• restore heart rhythm.

In this case, Metoprolol will be the best, since it is more active due to the larger amount of active ingredient in the drug. Its concentration in the blood plasma remains for up to 12 hours, while its analog Anaprilin is eliminated from the body after 3-4 hours.

special instructions

Monitoring of patients using beta-blockers includes regular monitoring of blood pressure, pulse, and sugar levels. It is important to teach the patient to keep track of the pulse rate, and in case of bradycardia, he needs to seek the help of his attending physician.

Elderly people need to monitor the functioning of the renal system.

Metoprolol can cause peripheral arterial circulatory disorders.

Metoprolol is withdrawn gradually over at least 10 days.

Taking more than 200 mg per day leads to a decrease in cardioselectivity.

When taking the drug, it is possible to mask the clinical picture of thyrotoxicosis ( tachycardia ).

When planning a surgical intervention, it is necessary to notify the anesthesiologist about taking the drug Metoprolol, and do not stop taking the drug.

arterial hypotension , increasing bradycardia , ventricular arrhythmia , atrioventricular block, severe pathology of the liver and kidneys are registered in elderly people

Treatment is stopped if depression develops or skin rashes appear.

When taking the drug during pregnancy, it should be discontinued 48-72 hours before the expected birth.

Metoprolol has an effect on driving vehicles and performing complex work.

Recipe in Latin:

Rp: Metoprololi 0.05 D. td No. 100 in tab. S. 1 tablet. 2-3 times a day.

Metoprolol or Betaloc ZOK – which is better?

Manufacturer: AstraZeneca AB (Sweden)
Release form: tablets

Active ingredient: metoprolol succinate

Betaloc ZOK is a selective beta1-blocker. Its characteristic feature is the prolonged release of the active substance. This effect of the medication tablets helps maintain a constant concentration of the drug in the blood for 24 hours or more. It is prescribed for the following pathologies:

• angina pectoris;
• heart rhythm disturbance;
• arterial hypertension.

The drug is used for myocardial infarction after the acute phase, as well as to prevent the development of a repeated acute ischemic state.

According to reviews from cardiologists, the best treatment for coronary heart disease, arrhythmia and high blood pressure is Betaloc ZOK. This is a long-acting drug, the concentration of which in the blood is maintained for a day or more.

It is well tolerated by patients, has a mild effect and rarely causes side effects. The Betaloc analogue is convenient to take, as it is taken once a day.

Metoprolol analogs

Level 4 ATC code matches:
Biol

Metocard

Metozok

Nebilet

Nebilong

Betaxolol

Bisogamma

Aritel

Cordinorm

Vasocardin

Corvitol

Bidop

Bisoprolol

Nebivolol

Biprol

Bisoprol

Concor Cor

Lokren

Concor

Niperten

Metoprolol-Acri, Metoprolol-Ratiopharm, Metoprolol-OBL, Metoprolol Organica, Metoprolol Zentiva are synonymous drugs.

The following analogues of Metoprolol are also distinguished:

• Egilok
• Betalok
• Metocard
• Metocore
• Serdol
• Anepro
• Vasocardin
• Corvitol
• Metobloc
• Metoprol
• Emzok

Metoprolol or Egilok – which is better?

Manufacturer: Egis (Hungary)
Release form: tablets

Active ingredient: metoprolol

Metoprolol and its analogue Egilok have the same active ingredient. Both drugs actively stop attacks of atrial fibrillation and tachycardia, reduce pulse and blood pressure to normal within 2 weeks of taking the drug. Egilok, with fewer side effects, is well tolerated by patients.

According to doctors, the best results are observed with treatment with Egilok. This is a “purer” drug, since higher quality raw materials are used in its production.

Metoprolol price, where to buy

The price of Metoprolol in tablets of 50 mg is on average 40 rubles per pack of 30 pieces.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine

ZdravCity

• Metoprolol tab.
  50 mg n30MEZ FSUE 54 RUR order
• Metoprolol Organika tablets 50 mg 30 pcs. JSC Organika

  29 RUR order

• Metoprolol Retard-Akrikhin tablets p.p.o. prolonged action 100 mg 30 pcs. JSC Akrikhin

  RUR 358 order

• Metoprolol tablets 50 mg 30 pcs. Ozon LLC

  33 rub. order

• Metoprolol-Akrikhin tablets 50 mg 30 pcs. JSC Akrikhin

  55 rub. order

Pharmacy Dialogue

• Metoprolol (25 mg tablet No. 60) Organics (Novokuznetsk Autonomous Okrug)

  64 RUR order

• Metoprolol (25 mg tablet No. 60) Ozon LLC

  60 rub. order

• Metoprolol retard-Akrikhin extended-release tablets 50 mg No. 30 Akrikhin OJSC

  RUB 216 order

• Metoprolol retard-Akrikhin tablets 100 mg No. 30 Akrikhin OJSC

  RUB 274 order

• Metoprolol retard-Akrikhin extended-release tablets 25 mg No. 30 Akrikhin OJSC

  RUB 171 order

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Pharmacy24

• Metoprolol tartrate 50 mg No. 20 tablets PAT "Farmak", Ukraine
  13 UAH. order
• Metoprolol-KMP 50 mg N30 tablets PAT "Kievmedpreparat", Ukraine

  11 UAH order

• Metoprolol tartrate 100 mg No. 20 tablets PAT "Farmak", Ukraine

  16 UAH order

• Metoprolol-KMP 100 mg N30 tablets PAT "Kievmedpreparat", Ukraine

  20 UAH order

Coronal

Manufacturer: AS Zenvita (Czech Republic)
Release form: tablets

Active ingredient: bisoprolol

Coronal is a selective beta-blocker. Under the influence of the medication, blood pressure is reduced, heart rhythm is restored, and angina attacks are prevented during myocardial ischemia.

The Coronal analogue, after oral administration, is well absorbed into the bloodstream and 90% of the medication enters the blood plasma, reaching its maximum after 2–3 hours. The drug is prescribed at a dose of 2.5-5 mg with possible adjustment according to indications.

Analogues of the drug Metoprolol Succinate

Active analogues of the drug Metoprolol Succinate:

• Betalok;
• Vasocardin;
• Corvitol;
• Metozok;
• Metocard;
• Metolol;
• Serdol;
• Egilok;
• Emzok.

Diseases associated with disruption of the heart and blood vessels cannot be ignored. If your blood pressure regularly increases, you should consult a doctor who will conduct an examination to identify the reasons for the persistent increase. For hypertension, the doctor will prescribe medication.

If a doctor prescribes Metoprolol, you cannot decide on its own to discontinue it or replace it with analogues. You should consult your doctor before you start taking Metoprolol replacement.

Metoprolol in the pharmacotherapy of coronary heart disease and concomitant pathologies

Coronary heart disease (CHD) is the most common reason for adults visiting medical institutions among all cardiovascular diseases in our country. The frequency of this pathology reaches 28% of cases. According to the Russian register of acute coronary syndrome, in almost half of patients with acute coronary insufficiency, the first manifestation of coronary artery disease is myocardial infarction. Therefore, it can be assumed that only 40–50% of all patients with coronary artery disease are aware of the presence of the disease and receive appropriate treatment, while in 50–60% of cases the disease remains unrecognized [1]. This actualizes the topic of clinical examinations, screening identification of risk factors and adequate treatment of pathological processes leading to vascular accident. Prescribing complete drug treatment can improve the quality of life and significantly reduce the incidence of complications and mortality among people with chronic forms of coronary artery disease. Recommendation documents in recent years systematize medications taking into account the strength of the evidence base in terms of the effect on pain and/or exercise tolerance in patients with angina pectoris. A special role is given to drugs that can improve prognosis and reduce the risk of disability and serious cardiovascular events.

Antianginal drugs that can reduce the frequency, duration and intensity of angina attacks include nitrates, calcium antagonists, and beta-blockers [2]. According to modern clinical guidelines for the treatment of stable coronary artery disease, angina pectoris is an indication for the prescription of beta-blockers [3]. Traditionally, in cardiology, preference is given to selective beta-blockers. Metoprolol tartrate has been used as an antianginal agent for more than twenty years. The mechanism of the antianginal action of the drug has been studied in detail. The “Pharmacodynamics” section of the instructions for the state register of metoprolol tartrate drugs emphasizes the ability of the drug to reduce myocardial oxygen demand by reducing systemic blood pressure, heart rate and myocardial contractility. By lengthening diastole when taking metoprolol, blood supply and oxygen uptake by the myocardium with impaired blood flow are improved. Therefore, for exertional angina, the drug reduces the number, duration and severity of attacks, as well as asymptomatic manifestations of ischemia, and improves the patient’s physical performance [4]. If symptoms are not well controlled, a combination of beta-blockers with dihydropyridine calcium antagonists is recommended [5,6].

In addition to its antianginal properties, metoprolol is a typical antihypertensive drug. The results of a large-scale meta-analysis by M.Law et al indicate that beta-blockers as initial therapy prevent coronary outcomes [7]. In arterial hypertension (AH), metoprolol reduces blood pressure (BP) by slowing the rhythm. The long-term antihypertensive effect is associated with a gradual decrease in total peripheral resistance. In hypertension, long-term use of the drug leads to a statistically significant decrease in the mass of the left ventricle and an improvement in its diastolic function [4]. The greatest effectiveness of beta-blockers was detected when used by patients with concomitant cardiac pathology, in particular, coronary artery disease and hypertension. The combination of coronary artery disease and hypertension is an almost daily clinical situation in the real practice of internists working both in hospitals and in outpatient settings. Among outpatients with cardiovascular diseases, the incidence of the combination of hypertension and ischemic heart disease reaches 67%. This result is known from the data of the Russian PREMIER study, conducted in 14 cities of Russia with the participation of more than 14,000 patients [8]. Similar data were published in the REACH (Reduction of Atherothrombosis for Continued Health) registry. Arterial hypertension in patients with coronary artery disease occurred in more than 80% of cases [9].

The recommended target blood pressure level for patients with hypertension and coronary artery disease is less than 140/90 mm Hg. Art. [10]. In this regard, drugs with two indications are of particular interest: arterial hypertension and coronary heart disease. Of the listed antianginal drugs, only calcium antagonists (dihydro- and non-dihydropyridine) and beta-blockers have such indications. It should be noted that the doses of the same drug in the treatment of different nosologies may differ, despite the common pathogenetic processes. Thus, in accordance with the instructions of the State Register of Medicines (GRLS), for hypertension, the initial dose of metoprolol tartrate is 25-50 mg twice a day, if necessary, the daily dose is gradually increased to 100-200 mg/day or another antihypertensive drug is added [4 ]. The usual daily dose after myocardial infarction is 100-200 mg/day, divided into 2 doses. Concomitant renal pathology in patients does not require a change in dosage regimen for any of the indicated nosologies. Due to the low binding of metoprolol to plasma proteins (5-10%), dose reduction in liver cirrhosis is also not recommended and may only be required in severe liver failure [4]. For angina pectoris, the initial dose of metoprolol tartrate is 25-50 mg, it can be taken two to three times a day with a gradual increase to 200 mg/day.

Blood pressure control in hypertensive patients with coronary artery disease is important, since the risk of developing recurrent coronary events largely depends on blood pressure levels [11]. However, it is necessary to remember the threshold value of DBP level is 70-75 mmHg. Art., in which a further decrease may be accompanied by a worsening of the disease.

In hypertensive patients who have suffered a myocardial infarction, early administration of beta-blockers reduces the risk of recurrent infarction and death [10-12]. A meta-analysis by Law MR showed that beta-blockers are highly effective in preventing cardiovascular events in patients with a recent myocardial infarction [7]. The results of the metoprolol study (Göteborg Metoprolol Trial) also indicate the high effectiveness of the drug in patients after myocardial infarction: the use of metoprolol for 90 days reduced mortality by 36%. This effect persisted regardless of age, previous infarction, or history of beta-blocker use. After three months, all patients were recommended to continue taking the drug, and the difference in mortality between the placebo group and the control group remained. Fewer episodes of ventricular fibrillation were recorded with metoprolol than in the placebo group (six versus 17 patients). In the metoprolol group, lidocaine, furosemide and analgesics were used less frequently [13].

In myocardial infarction, metoprolol is known to reduce mortality rates by reducing the risk of sudden death. This effect is primarily associated with the prevention of episodes of ventricular fibrillation. A reduction in mortality can be observed in both the early and late phases of myocardial infarction, in high-risk patients and patients with diabetes mellitus [4].

The delayed positive effect may be associated not only with the specific properties of beta-blockers. A significant role is assumed to be played by factors such as limiting the damaging effects of hyperactivation of the sympathetic nervous system, blocking the release of free fatty acids from adipose tissue caused by catecholamines, reducing oxidative stress, and reducing insulin resistance [14].

The effectiveness of long-term use of beta-blockers after myocardial infarction has been shown in a large number of studies [15]. However, these studies were generally conducted before the introduction of modern reperfusion techniques and drug therapy. However, in the absence of contraindications, beta-blockers are considered recommended for all patients who have suffered a myocardial infarction. They are most effective in patients with reduced left ventricular ejection fraction [15].

In addition to hypertension, which makes a dominant contribution to the statistics of death from coronary artery disease, there is another strategic component of hemodynamics - heart rate (HR), which is also influenced by beta-blockers and calcium antagonists, excluding the subgroup of dihydropyridines. Taking into account the contraindications to non-dihydropyridine calcium antagonists (verapamil, diltiazem) in chronic heart failure (CHF) and a significant amount of positive evidence confirming the effects of suppressing sympathetic activation, beta-blockers are becoming the dominant alternative in the combination of hypertension, tachyforms of arrhythmias and CHF. The fact of the relationship between high heart rate and mortality and other cardiovascular outcomes has been proven in a number of observational and epidemiological studies [16-20].

The results of the Framingham study showed an increase in both overall and cardiovascular mortality in patients with arterial hypertension, regardless of gender and age, with increasing heart rate. It is known that for every 40 beats per minute, the odds ratio of death from complications of cardiovascular disease was 1.68 and 1.70, and death from any cause was 2.14 and 2.18, respectively, for men and women [21]. Heart rate is the target parameter for exertional angina. The target heart rate, according to the results of a number of studies, was 55-60 beats per minute [22,23]. Cordero A et al [24] conducted an observational, multicenter study that included almost three hundred thousand patients with coronary artery disease. Compared with other drugs (including non-dihydropyridine calcium antagonists), patients receiving beta-blockers (atenolol, bisoprolol, metoprolol) had a significantly lower heart rate (67.2 versus 73.0 beats/min, P <0.01). Metoprolol, independently of other factors (OR: 1.29, 95% CI: 1.04 -1618; P = 0.04), was associated with heart rate control. At the same time, the authors concluded that in everyday practice, heart rate control in patients with coronary artery disease is insufficient.

A number of similar studies have attempted to determine whether patients achieve chronotropic therapeutic goals in real-life clinical practice. According to international registries, the proportion of patients who reached a heart rate of 55-60 beats/min does not exceed 22%. In twenty centers in 6 cities of the Russian Federation, the heart rate of patients (average age 64 ± 10 years) with angina pectoris FC I - III, taking a beta-blocker for at least two months at a constant dose for 4 weeks before inclusion in the program, was assessed. The proportion of patients with achieved target heart rate was 15.5% [25]. Similar data were obtained in a study designed to determine the adequacy of beta-blockers in outpatient settings in patients with angina pectoris [26]. Over 6 months, 2226 outpatients with stable coronary artery disease and a resting heart rate of more than 60 beats/min were registered. Overall, 45.4% of patients with CAD were not on beta blocker therapy. It is interesting to note that the heart rate values ​​in men were lower than in women. A multiple regression analysis was performed that included beta blocker use as an independent variable. It was found that non-use of beta blockers, female gender (OR 2.55), NYHA classes III-IV CHF (OR 1.62), smoking (OR 0.89) and increased body mass index (OR 0.14) are independent determinants of heart rate in peace. It was proven that the lack of use of beta-blockers (OR 3.35) was the dominant factor in the increase in heart rate, independent of other parameters. Heart rate in patients treated with beta-blockers was significantly lower than in patients not treated (73.6 ± 10.0 vs. 77.1 ± 10.4, P < 0.0001), although it often did not reach values ​​less than 60 beats/min.

In 2014, data from the CLARIFY prospective registry were published [24]. Data from 32,914 patients with angina, myocardial infarction and heart failure from 45 countries were analyzed; 75% of these patients were receiving beta blockers and had a heart rate of 68 ± 11 beats/min. Rates of beta blocker use varied by geographic region (87% to 67%). The main drugs used were bisoprolol (34%), metoprolol tartrate (16%) or succinate (13%), atenolol (15%) and carvedilol (12%); the mean doses were 49%, 76%, 35%, 53%, and 45% of the maximum doses, respectively. Patients, regardless of gender, over the age of 65 years were more likely to receive beta blockers than patients ≥ 75 years (P < 0.0001). Patients with heart rate ≤ 60 bpm received more intense beta blocker regimens than patients with heart rate ≥ 70 bpm (P < 0.0001). Patients with angina, previous myocardial infarction, heart failure, and hypertension were more likely to receive beta blockers (all P <0.0001), while patients with peripheral arterial disease and asthma/COPD were less likely to receive beta blockers (P <0.0001). The authors emphasize that heart rate is not well controlled in many patients, despite clinical recommendations for the management of CAD.

The choice of a beta-blocker within a class is based on the absence of intrinsic sympathomimetic activity, prolonged action, and a convincing evidence base for effectiveness and tolerability [2,10-12]. In addition, it is important that the instructions for the drug contain a wide range of comorbid conditions pathogenetically associated with IHD. The possibility of using one drug for several indications significantly reduces the risks of negative pharmacological reactions of both pharmacokinetic and pharmacodynamic nature. The ability of an antianginal drug to have a negative bathmotropic effect is especially relevant, because IHD is often accompanied by ectopic cardiac activity. Unlike nebivolol, betaxolol, carvedilol, bisoprolol, metoprolol has indications related to rhythm generation disorders [4]. In particular, metoprolol tartrate is indicated for supraventricular tachycardia, ventricular extrasystole, as well as for functional disorders of cardiac activity accompanied by tachycardia. According to the instructions, the drug is prescribed from 25-50 mg/day with a possible dose increase to 200 mg/day. In the “Standard of emergency medical care for tachycardias and tachyarrhythmias” [27], metoprolol is the only selective beta-blocker proposed for the care of adults with ventricular and supraventricular tachycardia, atrial fibrillation and flutter.

Therefore, current guidelines recommend beta blockers along with calcium antagonists as first-line treatment to control angina symptoms and heart rate. There is a significant dissonance between the proven facts about the need for drug reduction of rhythm in patients with coronary artery disease and real clinical practice. Often, patients either do not receive beta-blockers or take doses that are insufficient to maintain target heart rates. It is necessary to remember the relevance of the recommendations of experts from the European Society of Cardiology, focusing on the priority of prescribing beta-blockers. The choice of a selective beta-blocker metoprolol with a long-term mechanism of action and the presence of indications in the instructions related to tachyforms of arrhythmias and/or hypertension will contribute to both the secondary prevention of complications of coronary artery disease and the leveling of angina attacks, which will improve the quality of life of patients.

Literature

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