What are the common uses of metoprolol. How does metoprolol affect heart rate. What are the potential side effects of metoprolol. Which medications interact with metoprolol. Who should avoid taking metoprolol. What are the different dosage forms of metoprolol. How much does metoprolol typically cost.

Understanding Metoprolol: A Powerful Beta Blocker

Metoprolol, marketed under brand names such as Lopressor, Toprol, and Toprol XL, is a widely prescribed medication belonging to the beta blocker class. These drugs are designed to reduce the strain on the heart, making them invaluable in treating various cardiovascular conditions. But how exactly does metoprolol work, and what should patients know before starting this medication?

How Does Metoprolol Function in the Body?

Metoprolol’s primary mechanism of action involves blocking epinephrine (adrenaline) from binding to beta receptors in the heart muscle. This blockade results in several beneficial effects:

• Decreased heart rate
• Reduced force of heart contractions
• Lowered blood pressure
• Improved chest pain symptoms

By modulating these cardiac functions, metoprolol effectively lightens the workload on the heart, making it a valuable tool in managing various cardiovascular conditions.

Common Uses of Metoprolol in Cardiovascular Care

Healthcare providers prescribe metoprolol for a range of heart-related conditions. What are the primary uses of this medication?

• Hypertension (high blood pressure) management
• Treatment and prevention of angina (chest pain)
• Heart failure therapy
• Control of fast or irregular heartbeats (e.g., atrial fibrillation, atrial flutter)
• Post-heart attack (myocardial infarction) care

The versatility of metoprolol in addressing multiple cardiovascular issues makes it a cornerstone in modern cardiac care. However, its efficacy must be balanced against potential side effects and interactions.

Navigating Metoprolol Side Effects: From Mild to Severe

Like all medications, metoprolol can cause a spectrum of side effects ranging from mild inconveniences to more serious concerns. Understanding these potential effects is crucial for patients and healthcare providers alike.

Common Side Effects of Metoprolol

Many patients experience mild side effects when starting metoprolol. These often subside as the body adjusts to the medication. Common side effects include:

• Skin rash or itching
• Gastrointestinal disturbances (nausea, vomiting, diarrhea, stomach pain)
• Mood changes, including depression
• Dizziness and vertigo
• Fatigue or tiredness
• Cold extremities
• Dry mouth and eyes
• Mild breathing difficulties
• Slight weight gain (average of 1.2 pounds)
• Sexual dysfunction

While these side effects are generally not cause for alarm, patients should report persistent or bothersome symptoms to their healthcare provider.

Serious Side Effects Requiring Immediate Attention

Some side effects of metoprolol can be more serious and may require prompt medical intervention. These include:

1. Bradycardia (excessively slow heart rate)
2. Hypotension (dangerously low blood pressure)
3. Exacerbation of asthma or COPD
4. Masking of hypoglycemic symptoms in diabetic patients
5. Heart block (disruption of the heart’s electrical system)
6. Worsening of heart failure symptoms

Patients experiencing any of these serious side effects should seek immediate medical attention. It’s important to note that women taking beta blockers like metoprolol may have a higher risk of heart failure during acute coronary syndrome (ACS) compared to men.

Critical Warning: The Dangers of Abrupt Discontinuation

The FDA has issued a black box warning, its most serious type, regarding the abrupt discontinuation of metoprolol. Stopping this medication suddenly can lead to severe consequences, including:

• Acute chest pain
• Increased risk of heart attack (myocardial infarction)

Can patients safely stop taking metoprolol if needed? Yes, but it must be done under close medical supervision. Healthcare providers will typically implement a gradual dose reduction plan to safely wean patients off the medication when necessary.

Metoprolol Interactions: Medications to Watch

Drug interactions can significantly impact the effectiveness and safety of metoprolol. What medications should patients and healthcare providers be aware of when considering metoprolol therapy?

• Monoamine oxidase inhibitors (MAOIs)
• Calcium channel blockers (e.g., verapamil, diltiazem)
• Other beta blockers
• Certain antiarrhythmic medications
• Some antidepressants
• Certain antipsychotic drugs

This list is not exhaustive, and patients should always consult their healthcare provider or pharmacist about potential interactions before starting metoprolol or any new medication.

Who Should Exercise Caution with Metoprolol?

While metoprolol is generally safe and effective for many patients, certain groups should use this medication with caution or avoid it altogether. Who are these individuals?

• Patients with severe asthma or COPD
• Individuals with certain types of heart block
• Those with severe peripheral artery disease
• Patients with pheochromocytoma (a rare adrenal gland tumor)
• Individuals with severe liver disease
• Pregnant women (especially in the second and third trimesters)

Healthcare providers will carefully weigh the risks and benefits of metoprolol for these patients, often considering alternative treatments or modified dosing strategies.

Metoprolol Formulations: Tailoring Treatment to Patient Needs

Metoprolol is available in various formulations, allowing healthcare providers to customize treatment plans. What are the different dosage forms of metoprolol?

• Immediate-release tablets
• Extended-release tablets (Toprol XL)
• Oral solution
• Injectable form (for hospital use)

The choice of formulation depends on factors such as the specific condition being treated, patient preferences, and individual response to the medication. Extended-release formulations, for example, may offer the advantage of once-daily dosing, potentially improving medication adherence.

The Cost Factor: Understanding Metoprolol Pricing

The cost of metoprolol can vary significantly depending on several factors. What influences the price of this medication?

• Brand name vs. generic formulations
• Dosage strength
• Quantity prescribed
• Pharmacy pricing
• Insurance coverage

Generic metoprolol is generally more affordable than brand-name versions. Patients can often find cost-saving opportunities by comparing prices at different pharmacies or using prescription discount programs. It’s important to discuss any cost concerns with healthcare providers, as they may be able to suggest more economical alternatives or assist in finding financial assistance programs.

Typical Price Ranges for Metoprolol

While prices can fluctuate, here are some general price ranges for metoprolol:

• Generic immediate-release tablets: $10-$30 for a 30-day supply
• Brand-name Lopressor: $50-$100 for a 30-day supply
• Generic extended-release tablets: $20-$50 for a 30-day supply
• Brand-name Toprol XL: $100-$200 for a 30-day supply

These prices are approximate and can vary based on location, pharmacy, and other factors. Patients should always check with their insurance provider and local pharmacies for the most accurate pricing information.

Metoprolol Side Effects: What to Watch Out For

1. What are the side effects of metoprolol?
2. Which drugs interact with metoprolol?
3. Who should avoid taking metoprolol?
4. Dosage forms of metoprolol
5. Cost of metoprolol

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

Metoprolol (brand name Lopressor, Toprol, Toprol XL) is a type of medication known as a beta blocker. This class of medications decreases strain on the heart. Metoprolol is most commonly used to prevent, treat, or improve symptoms for the following conditions (Morris, 2020):

• High blood pressure (hypertension)
• Chest pain (angina)
• Heart failure
• Fast, irregular heartbeat like atrial fibrillation or atrial flutter
• Heart attack (myocardial infarction)

Metoprolol works by stopping epinephrine (also known as adrenaline) from binding to beta receptors in your heart muscle. Blocking the beta receptors allows metoprolol to decrease the workload on the heart. Metoprolol causes your heart to beat slower and squeeze less forcefully, thereby lowering blood pressure and improving chest pain.

Metoprolol is an effective drug, but, like most medicines, it can have both mild and severe side effects.

Common side effects of metoprolol include (UpToDate, n.d.):

• Skin rash
• Itching
• Gastrointestinal problems like nausea, vomiting, diarrhea, or stomach pain
• Depression
• Dizziness
• Tiredness
• Vertigo
• Cold hands and feet
• Dry mouth
• Dry eyes and/or blurred vision
• Breathing difficulties like shortness of breath, wheezing, and cough
• Weight gain – 1.2 pounds of weight gain on average (Sharma, 2001)
• Sexual dysfunction

Black box warning from the FDA (the most serious warning they issue): Do not abruptly stop taking metoprolol without talking to your healthcare provider. Stopping metoprolol suddenly may cause chest pain or heart attack (myocardial infarction). If you need to stop metoprolol, your healthcare provider will help you decrease the dose gradually (FDA, 2006). Serious side effects of metoprolol include (UpToDate, n.d.):

• Slow heartbeat (bradycardia): One of the ways that metoprolol works is by decreasing the heart rate to lighten the load on the heart—so a somewhat lower heart rate is expected. However, some people may experience a heart rate that is too low, causing fainting spells (syncope), dizziness, chest pains, fatigue, and confusion. 
• Low blood pressure (hypotension): Metoprolol is often given to help lower blood pressure in people with high blood pressure or other heart conditions. Sometimes, the blood pressure can drop too low. Symptoms include dizziness, fainting, blurred vision, fatigue, shallow breathing, rapid pulse, and confusion. Your blood pressure may drop only after standing up from a sitting or laying down position—this is called orthostatic hypotension. Severely low blood pressure is a life-threatening emergency. 
• Worsening asthma or chronic obstructive pulmonary disease (COPD): Metoprolol, a beta-blocker, has a small risk of triggering an asthma attack or worsening COPD by causing bronchospasm (tightening of the airways). This is because the beta receptors that line the lungs are similar to the ones that metoprolol targets in the heart and blood vessels. However, metoprolol is less likely to cause breathing issues than some of the other beta blocker drugs.
• Masking of hypoglycemic symptoms: When your blood sugar drops too low, your body gives you signals to let you know so that you can replenish your glucose reserves—these signals typically include shakiness, anxiety, confusion, rapid heartbeat (palpitations), lightheadedness, etc. However, metoprolol may mask these signs, preventing you from realizing that your blood sugars are too low. Keeping your blood sugars too low for too long can lead to seizures, unconsciousness, and even death in rare cases.
• Heart block: Metoprolol can interfere with the normal electrical system of the heart; this can lead to heart block, which causes an irregular heartbeat.
• Worsening of heart failure: People with heart failure who are taking metoprolol may notice a worsening of their heart failure symptoms; this may be especially true for women (DailyMed, 2018). An American Heart Association journal reported that women who are taking beta blockers (like metoprolol) have a higher risk of heart failure during an acute coronary syndrome (ACS) than men (Bugiardini, 2020).

This list does not include all possible side effects and others may exist. Check with your pharmacist or healthcare provider for more information.

Before starting metoprolol, or any other new medication, seek medical advice about potential drug interactions. Medicines that may interact with metoprolol include (DailyMed, 2018):

• Monoamine oxidase inhibitors (MAOIs): These drugs are often used to treat depression and may increase the effects of metoprolol and can potentially increase side effects. Examples include isocarboxazid, phenelzine, selegiline, and tranylcypromine.
• Epinephrine: People who take metoprolol and use epinephrine for severe allergic reactions, may find that the usual dose of epinephrine does not work as well. If you have a history of severe allergic reactions, be sure to let your healthcare provider know that you are taking a beta blocker.
• Inhibitors of the CYP2D6 system: Metoprolol is broken down by the CYP2D6 system in the liver. Drugs that interfere with the CYP2D6 system prevent metoprolol from being metabolized. As a result, you can have double the typical amounts of metoprolol circulating in your bloodstream; this increases your risk of side effects. Examples of these medications include quinidine, fluoxetine, paroxetine, and propafenone.
• Medications that slow the heart rate: Since metoprolol lowers the heart rate, combining it with other drugs that also decrease the heart rate increases your risk of having a very slow heart rate (bradycardia). Examples include digoxin, clonidine, diltiazem, and verapamil.
• Sildenafil (brand name Viagra; see Important Safety Information) or other phosphodiesterase-5 (PDE5) inhibitors: Metoprolol may cause more of a drop in blood pressure if taken with PDE5 inhibitors.
• Alcohol: Some types of metoprolol (namely metoprolol succinate) are available in an extended-release formulation. In the presence of alcohol, this extended-release action is sped up, and the metoprolol is released into your system faster.

This list does not include all possible drug interactions with metoprolol and others may exist. Check with your pharmacist or healthcare provider for more information.

Certain groups of people should avoid using metoprolol or use it with caution (DailyMed, 2018):

• People with asthma: Metoprolol may trigger an asthma attack, and people with asthma or COPD should avoid using it. Make sure your healthcare provider is aware that you have asthma before starting metoprolol.
• People with diabetes: Metoprolol can block the signs of low blood sugar, like increased heart rate, sweating, and tremors.
• People with a slow heart rate (bradycardia) or low blood pressure (hypotension): Metoprolol lowers blood pressure and heart rate.
• Pregnant women: The U.S. Food and Drug Administration (FDA) has deemed metoprolol as pregnancy category C; this means that there is not enough information to determine the risk to the pregnancy (FDA, 2006). Women and their healthcare providers should weigh the benefits of taking metoprolol against the risk to the fetus.
• Nursing mothers: Metoprolol does get into the breastmilk, in small quantities, and no adverse effects have been reported. Women and their healthcare providers should weigh the risks and benefits of the medication (FDA, 2006).
• People with liver disease: Since metoprolol is broken down by the liver, people with liver disease may have higher than expected levels of metoprolol in their system. They may need a lower dose of metoprolol (DailyMed, 2018).

This list does not include all possible at risk groups and others may exist. Check with your pharmacist or healthcare provider for more information.

There are two different types of metoprolol: metoprolol tartrate and metoprolol succinate. Metoprolol tartrate (brand name Lopressor) is used in immediate-release tablets and comes in 25 mg, 37.5 mg, 50 mg, 75 mg, and 100 mg pills. Metoprolol succinate (brand name Toprol XL) is used in the extended-release capsules and tablets and comes in 25 mg, 50 mg, 100 mg, and 200 mg pills. The specific dose recommended by your healthcare provider will vary depending on the condition being treated, as well as your other medical issues.

Both forms of metoprolol are available as generic medications. Metoprolol tartrate ranges from $4 to $9 for a 30-day supply, depending on the dose. Metoprolol succinate varies from $6 to $18 for a 30-day supply, again depending on the dose.

1. Bugiardini, R., Yoon, J., Kedev, S., Stankovic, G., Vasiljevic, Z., Miličić, D., et al. (2020). Prior Beta-Blocker Therapy for Hypertension and Sex-Based Differences in Heart Failure Among Patients With Incident Coronary Heart Disease. Hypertension https://doi.org/10.1161/HYPERTENSIONAHA.120.15323. Retrieved from https://www.ahajournals.org/doi/10.1161/HYPERTENSIONAHA.120.15323 
2. DailyMed. (2018). U.S. National Library of Medicine and the National Institutes of Health (NIH): Metoprolol succinate capsule, extended-release. Retrieved on Aug. 12, 2020 from https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90aa06a3-100f-4466-b950-506303707b01
3. Morris, J. & Dunham, A. (2020). Metoprolol. StatPearls [Internet]. Retrieved on Aug. 12, 2020 from https://www.ncbi.nlm.nih.gov/books/NBK532923/ 
4. Sharma, A. M., Pischon, T., Hardt, S., Kunz, I., & Luft, F. C. (2001). Hypothesis: β-Adrenergic Receptor Blockers and Weight Gain. Hypertension, 37(2), 250–254. doi: 10.1161/01.hyp.37.2.250. Retrieved from  https://www.ahajournals.org/doi/full/10.1161/01.hyp.37.2.250
5. UpToDate. (n.d.). Metoprolol: Drug Information. Retrieved on Aug. 12, 2020 from https://www.uptodate.com/contents/metoprolol-drug-information?search=metoprolol&source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F195759
6. U.S. Food and Drug Administration (FDA). (2006). Metoprolol succinate, extended-release tablets. Retrieved on Aug. 12, 2020 from https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/019962s032lbl.pdf

Dr. Mike is a licensed physician and the Director, Medical Content & Education at Ro.

Your Good Health: Metoprolol can lower heart rate excessively

Dear Dr. Roach: My husband has been on metoprolol for about eight years. He was prescribed that medication right after he had a stent put in due to a clogged heart vessel. He is doing very well. His recent stress test was normal.

Dear Dr. Roach: My husband has been on metoprolol for about eight years. He was prescribed that medication right after he had a stent put in due to a clogged heart vessel. He is doing very well. His recent stress test was normal. The metoprolol took his heart rate down to a pulse of between 55 and 60 shortly after he started it. He is an active 79-year-old and in good shape. But he was told years ago, when the metoprolol lowered his pulse, that he may eventually need a pacemaker.

If the metoprolol is giving him a lower heart rate, causing a future need for a pacemaker, I would think the cardiologist would just give him a different blood pressure prescription that doesn’t lower the heart rate. He does not want a pacemaker due to a medication side-effect. Do you think a replacement for the metoprolol would keep his pulse in the normal range and dismiss the thought of a future pacemaker?

N.F.

Metoprolol — commonly used in patients with coronary artery blockages — is a beta blocker, and it works mainly by slowing the heart rate down and by decreasing how hard it contracts. Beta blockers reduce the risk of further heart attacks and death in people with coronary artery disease, and they should be given to most people with coronary artery disease unless there is a good reason not to. They also may act to reduce rhythm disturbances by counteracting adrenaline in the blood.

A heart rate of 55-60 is not unusual in people taking metoprolol. However, if a person had a heart rate that slow without a beta blocker, a doctor would be concerned that they would eventually develop symptoms from that slow of a heart rate. Symptomatic slow heart rate (“bradycardia,” from the Greek roots) is a clear indication for a permanent pacemaker, and extreme bradycardia (below 40) gets most cardiologists concerned enough to start thinking about a pacemaker even without symptoms.

In your husband’s case, if his heart rate were to prove too slow, his cardiologist would likely reduce the dose of the metoprolol, or even switch it out for a different drug.

Dear Dr. Roach: I am an 86-year-old man in pretty good health. I ran my entire life, including 10K and 10-mile races until my left hip was replaced three times. Is there any documented health benefit from taking 250 steps per hour (that’s the minimum on my smartwatch) daily? I am no longer doing duration exercises such as walking.

D.M.

Any exercise is better than none. If you are taking 250 steps for every hour you’re awake, that’s 4,000 steps per day, which is a lot better than some other people get. You don’t need 10,000 steps a day to get benefit.

The running and other exercises you did have been part of the reason you have enjoyed mostly good health until age 86.

Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers can email questions to [email protected]

Answers to questions

Oksana Mikhailovna Drapkina , professor, doctor of medical sciences:

– Dear colleagues, we received a lot of questions, and, in general, we need to meet 20 minutes, so let’s – as we spoke. The first is Professor Shevchenko Alexey Olegovich.

Aleksey Olegovich Shevchenko , professor, doctor of medical sciences:

– Yes, thank you, dear colleagues. Indeed, there are several questions. In turn.

“Which is better for the treatment of paroxysmal sinus tachycardias: bisoprolol or metoprolol?”

I will answer this way: beta-blockade. I’m not kidding, I just would like to clarify: even the very first beta-blocker Anaprilin (Propranalol), which appeared in 1964, was the first publication. And, despite the fact that in 1968 it was positioned primarily as an antihypertensive drug, the first publications just concerned the effectiveness of Propranolol in patients with paroxysmal sinus tachycardia in the England Journal of Medicine. And all beta-blockers have this property, and all beta-blockers are good. Another thing is when you start comparing the best with the good. There really were head-to-head comparisons, but, unfortunately, I did not see a comparison of Bisoprolol with Metoprolol. I saw comparisons of Metoprolol with Carvedilol, Bisoprolol with Carvedilol, Carvedilol with Propranolol, but, unfortunately, I did not see Bisoprolol and Metoprolol directly. But here, probably, it does not matter where to start.

The main principle is that beta-blockers effectively reduce the heart rate in patients with sinus tachycardia, and with increasing doses, side effects may occur. Against the background of the appearance of known side effects that are not worth listing now, one should not rush to cancel beta-blockers, but still switch to a more cardioselective one. Once again, Bisoprolol and Nebivolol are beta-blockers with the highest cardioselectivity available. I guess that’s how I would answer your question.

Second question in English, quote. Well, firstly, dear colleagues, let me answer in Russian, because even if a colleague was English-speaking, he understood what was discussed in the report. And, of course, I would like to give a compliment. We always insist: “Dear doctors, try, as Kozma Prutkov said, “to look at the root”, always look at original works.” Here is a small quote from Sripal Bangalore, and most likely it is one of the publications in the Journal of the American College of Cardiology. It is in English, but I will immediately read in Russian: “In an observational study involving patients with either only risk factors for coronary heart disease, or a previous myocardial infarction, or with coronary heart disease without myocardial infarction – in these patients, the use of beta-blockers did not was associated with a reduced risk of composite cardiovascular events.” Sripal Bangalore.

Here I would like to say that it was the same Sripal Bangalore, a respected American professor who was one of the first to raise and, perhaps, most often raises the topic (and just on the pages of the Journal of the American College of Cardiology) about the fact that beta- blockers as a class are not quite simple. And what I talked about in the report very briefly, but, nevertheless, a really large meta-analysis, primarily with the participation of Atonalol, showed some shortcomings that had their own explanations. Secondly, here in this quote, an observational study is mentioned. With all the advantages, the observational study belongs to the class of the so-called “hypothesis-generating”, that is, they allow one to assume. And they do not always reflect the true essence … As, remember, with hormone replacement drugs, when in observational studies we saw an almost two-fold reduction in mortality and adverse events of cardiovascular diseases, while a prospective study showed that all – That’s a little different. It’s exactly the same here: yes, observational studies, where a huge number of factors, in addition to the drug therapy taken, really show that we really doubt (and this was exactly what we were talking about, that we always have to doubt: we doubt our every act, every action, especially when it comes to the patient). But at the moment I would still like to say that a large number of prospective studies with beta-blockers show that they effectively reduce the risk of adverse cardiovascular events in heart failure, in secondary prevention in patients with atherosclerosis, and perhaps in many cases in primary prevention in patients with arterial hypertension and in a number of other situations.

Next question. If an elderly patient with isolated systolic arterial hypertension has elevated pulmonary artery pressure, what is the correct combination of antihypertensive therapy? Here I would like to quote again recent works, perhaps recommendations, perhaps observations, that all the same, in older people, all five classes of the main drugs that we use are equally effective. And here, probably, it will no longer be the age of the patient that will play a role, but comorbidities and the possibility of developing side effects, as well as the fact that arterial hypertension plays a leading role in the pathogenesis, because arterial hypertension is a polyetiological syndrome, a disease, and each patient has a ratio these mechanisms are different. But still, if there is a concomitant increase in pressure in the pulmonary artery, calcium antagonists should probably be in the first place; probably, it would be necessary to put thiazide or thiazide-like diuretics; maybe then after them it would be possible to take ACE inhibitors. Although, again, we immediately recall drugs like Sildenafil that affect phosphodiesterase, which are effective in patients with increased pressure in the pulmonary artery, although this no longer applies to the group of antihypertensive drugs.

Last question. How does bisoprolol affect central pulse pressure? I immediately say: I do not know the work with Bisoprolol, but I saw the work of physiologists with different beta-blockers, maybe there was Bisoprolol. At least it was shown that in apparently healthy volunteers, any decrease in pulse rate – whether it be a beta-blocker, whether it be a drug that selectively affects only the heart rate – this led in a short study to an increase in the central pulse pressure in the aorta. On the other hand, the pressure in the aorta was never measured in these cases in a direct way: no one in these patients inserted a transducer into the aorta, because it still increased the risk. The method of applanation tonometry was used, which is based on the fact that according to the pulse curve, with the help of a certain algorithm, the computer seemed to restore the pressure in the central aorta.

I repeat once again: a number of authors even showed that with Verapamil, which is a calcium antagonist and pulse-lowering, this effect is also possible, but due to the influence of this calcium antagonist on the tone of the vascular wall (calcium antagonists reduce the tone of the vascular wall more pronouncedly, than beta-blockers) this increase was not as pronounced. And, again, let’s recall the latest recommendations for the treatment of patients with arterial hypertension, when we have combination therapy in the first place, and it is still better to combine beta-blockers not with diuretics, but with calcium antagonists such as Amlodipine, where this effect will be minimized.

Drapkina O.M. :

– How do you feel about the prescription of Metformin for metabolic syndrome? I’m fine.

Has statins and ACE inhibitors been studied for epicardial fat layer thickness? No, it hasn’t.

How does Lisinopril affect non-alcoholic fatty liver disease? I would say that it is not that it affects non-alcoholic fatty liver disease, but that it affects the level of blood pressure in patients with metabolic syndrome who have non-alcoholic fatty liver disease, but the increase in transaminase levels has not been carried out against this background. Although, bearing in mind that this is pre-fibrosis, we can say that the effect on the rhinin-tensino-aldosterone system and in the liver is good. What is good for the heart is good for the liver.

Good afternoon. Grodno Medical University, Belarus. What are the criteria for the diagnosis of non-alcoholic fatty liver disease? In fact, it is an invisible disease. It may not appear in any way, but if there is a change in the echo signal on ultrasound, if the level of transaminases is elevated, while there is fatty infiltration on histological examination of more than 5% without alcohol, we can make this diagnosis.

How long should bifidum bacteria be used together with antihypertensive drugs? Alma-Ata. Use as much as you want. I just want to say that the data that Olga Nikolaevna spoke about is the influence of flora on obesity – here, of course, the preparation must contain two forms of bacteria: both bifidum- and lacto-. In Russian practice, there is now such a drug – Florasan, therefore, probably, it is the most indicated.

Is Diroton the drug of choice in patients with hypertension in combination with metabolic syndrome? Thank you. Kazakhstan, Shymkent. Dear colleagues, you know, after all, inhibitors are all different, and there is not enough data for me to say what will be the drug of choice. But if you’re talking about metabolic syndrome, it’s probably already a high risk, and you’ll go for combination therapy. Thank you.

Sergei Rudzherovich Gilyarevsky Professor, Doctor of Medical Sciences:

– High dose statins are a new trend. Isn’t it the intrigues of pharmaceutical companies in pursuit of profit when the patent protection for the main statins – Rosuvastatin, Atorvastatin – ended? In fairness, it must be said that the TNT, PROVE-IT studies were carried out when the patent protection was not over, just like the JUPITER study. So this is not a machination, it’s just a trend to prove that a more intensive statin regimen is more effective, and this has been proven. But it’s another matter that very often you can reach the target level using a lower dose of a statin, and, probably, under the intensive regimen, it should be understood first of all not the doses, but the achievement of the target cholesterol level, which we have talked about so much.

What course of therapy with Rosuvastatin should be carried out in patients with type 2 diabetes mellitus, and what dosages are most preferable? What course – in patients with diabetes, we probably do not conduct a course, that is, not probably, but definitely. If we decide to reduce the risk of complications with statins, then we prescribe constantly. But I think that the choice of statin is determined by the target level. The current recommendation is less than 1.8, so you can start with 10 milligrams, if not enough, you can add up to 20 milligrams.

Fenofibrate and statins, given the adverse interactions, it is scary to prescribe . .. Fenofibrate does not have much interaction with statins, and there were two studies: one was simply prescribed often off protocol – this is the FIELD study of fibrate and statin in diabetic patients, and already in the ACCORD Lipid study, fenofibrate was administered over a statin according to the protocol. And there were side effects, but not related to their interaction, but simply different. When are fibrates prescribed unambiguously? When the initial triglyceride concentration is more than 5 millimoles per liter, because from this level the danger of pancreatitis begins, and when we do not reach the target level of triglycerides when using statins, we also consider the addition of fibrates.

4 months of waiting for a decrease in CPK from 2800 on a dose of Vazelip 10 milligrams. Consultation at the Research Institute of Rheumatology, where they deal with this problem. The case is very instructive, extremely careless prescription of statins. Dear colleagues, in general, muscle disease can be both myopathy and myositis. This is a disease that is not so common, but it does occur, and it is not necessarily associated with the use of statins. Another thing is that against the background of the use of statins, some slight myopathy may be, and may not be so rare, but this is not of great clinical significance. I would like to emphasize once again that the question of the abolition of statins against the background of myopathy is accepted in two cases: either if the symptoms of myopathy are very pronounced, and the second – if the level of CPK exceeds 10 times the upper limit of normal. Therefore, here the issue must be resolved individually, but in your case, most likely, this is not related to the use of a statin, it is just an independent disease, especially since you correctly applied to the Institute of Rheumatology, which deals specifically with myopathies, inflammatory muscle diseases.

Prescribing high doses of statins 80 milligrams. How do you convince doctors to prescribe such doses and what to do with the appearance of complications? I want to say that after all, among the side effects of 80 milligrams of Atorvastatin, it was mostly an asymptomatic increase in transaminase levels. It is, in general, probably not so dangerous. But there is an alternative – 40 milligrams and 20 milligrams of Rosuvastatin. Such regimens of taking Rosuvastatin are no less, and perhaps even more effective in lowering cholesterol levels. When prescribing, no one is guaranteed against side effects, so the doctor, prescribing such a dose, always correlates the risk of side effects and always responds.

How would you rate the clinical presentation of a patient with ACS? How much statin myopathy has been encountered in your practice? How to evaluate the clinic, because the patient with ACS does not walk? Firstly, after percutaneous intervention, the patient walks after two or three days, and, accordingly, myopathy may already appear in him. But, again, if we prescribe a large dose of a statin even on the first day, then in order for myopathy to develop, some more time is needed, so, most likely, it will develop – if it develops suddenly – already at the outpatient stage. And evaluate by the clinic, by the symptoms and by the level of increase in the level of creatine phosphokinase, which in the case of myopathy rises much more, and then the MB fraction does not increase.

Is it possible to use rosuvastatin in young people as a preventive therapy? How long is therapy needed? Yes. Statin therapy is usually ongoing. You should not invest in statin prophylaxis if this prophylaxis is 2-4 months. That is, it is impractical to make any breaks, so the duration should be indefinitely long. Another thing is when to use it in very young people, that is, when the risk is less than 1% on the SCORE scale, then, in accordance with the recommendations, we start statin therapy at a level of low-density lipoprotein cholesterol of more than 4.9millimoles per litre. If there are any signs of atherosclerosis, then probably earlier.

What will happen to omega-3 polyunsaturated fatty acids now? The latest meta-analysis disappointed all cardiologists. I think that with omega-3 there will be nothing. This is the only way to answer, because there is no evidence base. Whether they will be applied depends on the relation to the evidence base.

Drapkina O. M. :

– You know, those who counter this say that this meta-analysis included everything in general – not only, for example, drugs, but also fish oil – something that is not drugs. How to answer this?

Gilyarevsky S.R. :

– Food products. There was already an article in the British Medical Journal, where it was shown that in general the prevention of stroke with omega-3s is associated with the use of fish. That is, those who ate fish had fewer strokes, those who took omega-3s did not. Therefore, a meta-analysis is a meta-analysis. It is, in fact, not needed, because there is a result of a large ORIGIN study, where this hypothesis was not confirmed, the omega study. Those who argue – we are open and do not feel … I believe that an expert in evidence-based medicine should not experience any emotions, because this is unprofessional.

Drapkina O.M. :

– How are you.

Gilyarevsky S. R. :

– Yes. Like me. No, of course, a person is weak, and therefore you also sometimes begin to experience, but this is wrong. When I experience – you tell me: “You are unprofessional.” So we have to wait for evidence. If new evidence emerges from well-designed studies showing that omega-3 polyunsaturated fatty acids affect prognosis, we will change our minds along with the entire cardiology world.

Maybe give patients a combination of ubiquinone and a statin right away? Coenzyme Q10 is being discussed – not confirmed. No need.

Which drug should be preferred in thin female patients aged 60-70 years with arterial hypertension, coronary artery disease and severe atherosclerosis? I think that either Atorvastatin or Rosuvostatin, because in this situation there is such a patient, and in thin patients, as Alexandra Nikolaevna says about even the paradox associated with obesity, atherosclerosis flows less favorably, so here it is necessary to reduce . ..

David Vasilyevich Nebieridze Professor, Doctor of Medical Sciences:

– For very thin people. Such a U-shaped curve.

Drapkina O.M. :

– David Vasilievich, but recently there was such a study when they showed that the outcome of cardiovascular events was best for those who had a body mass index of 24 to 29.9.

Nebieridze D.V. :

– That’s what I’m talking about. That is, there is such a point, such a U-shaped one, below which there is the same risk as in overweight patients.

Gilyarevsky S.R. :

– Still, these studies should be treated with caution, because they are observational.

In female patients taking long-term contraceptives, at what dosage should Rosuvostatin therapy be started? Hard to say. There is no evidence. There was evidence that the realization of the negative effect of contraceptives is associated with an increase in the level of C-reactive protein, so it can be assumed that taking statins will level out, but this is an assumption. There is no evidence. And in general, if the attitude towards hormone replacement therapy changes, it will probably be more relevant.

European cardiologists warn against prescribing a dose of 40 milligrams. Comment. First, it is not clear why? I think Rosuvostatin. However, I didn’t see any warnings. 40 milligrams has some kind of evidence base in the same LUNAR study, the METEOR study, and it must be said that in the course of these studies, the use of such a dose was safe. Another thing is that there is no data on the effect on the prognosis. But, perhaps, this is not so important.

Nebieridze D.V. :

– Which ACE inhibitor should be preferred for metabolic syndrome? Dear colleagues, I already said in my message that in order to finally judge which of the ACE inhibitors is better in a given situation, there should be comparative studies with endpoints. Unfortunately, there are no such studies on individual ACE inhibitors, but I can assume that the same Lisinopril that I spoke about, due to the fact that it improves tissue sensitivity to insulin, and this was shown in a solid study, probably is one of the best drugs of choice for metabolic syndrome. Although, I emphasize once again, this question can finally be answered only in a study when ACE inhibitors are compared, as they say, “face to face”.

Is there an interaction between Lisinopril and alcohol? This, too, I provoked with my performance. Lisinopril is indeed the only ACE inhibitor that does not lose its effectiveness in patients with hepatic diseases, including those of alcoholic origin. But, unfortunately, alcohol affects all drugs, reducing their effectiveness. Therefore, in my report, I said that in no case, if Lisinopril is the most effective ACE inhibitor, the patient should not be told to continue drinking and taking Lisinopril. Either one or the other is a joke. But it is better to refuse to drink Lisinopril.

But this question is more difficult. The most prescribed inhibitors in the US, Europe and Russia. Recently I saw an American review “The dynamics of prescribed ACE inhibitors.” And not because today I spoke mainly on Lisinopril. Indeed, there is a trend that both in the United States and in Europe, the prescription of Lisinopril comes to the fore.

Gilyarevsky S.R. :

– In America, at least, this is connected with the evidence base, after all, the ALLHAT study by American experts is still considered a trusted source.

Nebieridze D.V. :

– As for Russia, to be honest, I don’t have the latest data on which ACE inhibitors came out on top. But the trend around the world is clear that Lisinopril is really leading the way.

That’s about all the questions I have. Three questions.

– Thank you very much, we had a very interesting discussion.

Some aspects of the use of bisoprolol in cardiovascular disease | Oleinikova G.L.

Cardiovascular diseases (CVD) and their complications are the main causes of disability and high mortality in economically developed countries. In Russia, the trend of slow growth of these indicators has recently been maintained, and therefore, the issue of timely treatment and prevention of this pathology becomes especially relevant [1]. β-blockers have been widely used in the treatment of cardiovascular diseases for over 40 years. The main niches of their application are stable coronary heart disease (CHD), arterial hypertension (AH), myocardial infarction, chronic heart failure, and cardiac arrhythmias. In the US, β-blockers are the 4th most commonly prescribed drug. Since then, many clinical studies have been performed, which significantly expanded the scope of β-blockers in cardiology. In recent years, β-blockers are considered as drugs of first choice in the treatment of hypertension and coronary artery disease, which is reflected in many national and international clinical guidelines [2].

β-blockers are a large group of drugs, the main mechanism of action of which is the blockade of adrenoreceptors, which prevents the action on them of the mediator – norepinephrine, as well as catecholamines circulating in the blood. Norepinephrine, being a neurohumoral transmitter, causes a lot of adverse effects, the main of which is an increase in heart rate associated with sympathetic activation. Catecholamines have a direct effect on the growth factor of cardiomyocytes, stimulating the process of hypertrophy, and are a trigger of oxidative stress in programmed apoptosis [3]. Also, β-blockers affect the renin-angiotensin-aldosterone system (RAAS), inhibiting the release of renin by blocking β1-receptors in the juxtaglomerular apparatus of the kidneys.

The main actions of β – blockers are as follows [4,5]:

1. Antiischemic action due to a decrease in myocardial oxygen demand against the background of a decrease in heart rate, a decrease in contractility myocardial and systolic blood pressure; improvement of myocardial blood supply against the background of diastole lengthening and reduction of intramyocardial tension.

2. Antihypertensive effect by reducing cardiac output; inhibition of renin secretion, the formation of angiotensin II and aldosterone due to the blockade of β1-adrenergic receptors of the juxtaglomerular apparatus of the kidneys; blockade of presynaptic β-adrenergic receptors that promote the release of norepinephrine from sympathetic nerve endings; a decrease in the vasomotor activity of the central nervous system and a restructuring of the baroreceptor mechanisms of the aortic arch and carotid sinus.

3. Antiarrhythmic action by reducing heart rate, reducing spontaneous activation of ectopic pacemakers, slowing conduction and increasing the refractory period in the atrioventricular node, reducing the effect of catecholamines.

There are β1-selective (cardioselective) drugs that block predominantly β1-adrenergic receptors, and non-selective β-blockers that block ββ1- and ββ2-adrenergic receptors approximately equally.

Also, β-blockers differ in the presence of internal sympathomimetic activity, that is, the ability, along with the blockade, to simultaneously stimulate β-adrenergic receptors, as well as in the presence of additional properties, primarily vasodilating (carvedilol, nebivolol). The solubility of β-blockers in fats and water is important. By lipophilicity, all β-blockers can be divided into hydrophilic (atenolol, nadolol, sotalol), lipophilic (metoprolol, betaxolol, propranolol, etc.) and amphophilic (bisoprolol). A special place is occupied by bisoprolol. Being amphophilic, that is, soluble in both fats and water, this drug has two routes of elimination – renal excretion and hepatic metabolism. This ensures greater safety of use in patients with concomitant liver and kidney damage, elderly patients, as well as a low likelihood of drug interactions. Let us consider in more detail the use of bisoprolol in cardiology practice.

Pharmacokinetics
and pharmacodynamics of bisoprolol

The drug is almost 100% absorbed from the gastrointestinal tract. The half-life of bisoprolol is 10–12 hours [6], which makes it possible to prescribe it once a day. Bisoprolol is 50% metabolized in the liver by cytochromes CYP2D6 and CYP3A4 [7], and 50% of the drug is excreted unchanged by the kidneys [8].

Bisoprolol has a high cardioselectivity. Studies have shown that bisoprolol has 14–19times higher affinity for β1– than for β2–adrenergic receptors [9–12]. The high degree of selectivity of bisoprolol against β1adrenergic receptors, determines the high safety of the drug in a wide contingent of patients. For example, complications such as bradycardia, atrioventricular blockade, decompensation of heart failure, orthostatic hypotension, were observed only in 0.1-1% of patients.

Given the high selectivity, bisoprolol at therapeutic doses does not impair bronchial patency and respiratory function in patients with chronic obstructive pulmonary disease [13]. The study conducted by Chatterjee S.S., which was devoted to the study of the effects of bisoprolol in patients with bronchial asthma, showed that bisoprolol caused an insignificant decrease in FEV1 and airway resistance comparable to placebo [14]. Also, taking bisoprolol is not associated with the development of sexual dysfunction, which was confirmed in a study by Prisant L.M. et al., where the frequency of sexual dysfunction when taking bisoprolol did not differ from that when taking placebo [15]. Therefore, bisoprolol is the only b-adrenoblocker for which the absence of an effect on sexual function in men has been convincingly proven.

There was no effect of bisoprolol on carbohydrate metabolism, both in patients without its violation [16] and in patients with diabetes mellitus [17]. Finally, bisoprolol does not affect the content of cholesterol and lipoproteins in blood plasma [18,19]. So, in the study by Saku K. et al. there were no significant changes in the concentration of lipoproteins, apolipoproteins and lipoprotein a in the blood serum while taking bisoprolol for 12 months [20]. The drug has a moderate negative inotropic effect and only rarely causes clinically significant hemodynamic disturbances. In addition, bisoprolol does not have intrinsic sympathomimetic activity and does not prolong the QT interval [21].

However, do not forget that in some cases, bisoprolol, like other β-blockers, can increase sensitization to allergens, provoke an exacerbation of psoriasis. With pheochromocytoma, the use of bisoprolol is permissible only after the appointment of an α-blocker. With thyrotoxicosis, bisoprolol can “mask” the symptoms of this disease.

Consider in more detail the use of β-blockers, with an emphasis on bisoprolol, in various pathologies of the cardiovascular system.

β-blockers in the treatment of coronary artery disease, including in patients with myocardial infarction, have been used since the 60s of the XX century. A retrospective analysis of the Cooperative Cardiovascular Project, which included 200 thousand patients with MI, convincingly showed a decrease in mortality when taking β-blockers, regardless of gender, age, comorbidities, ejection fraction and heart rate [22]. With regard to bisoprolol, one of the most important studies is the randomized controlled trial TIBBS, which examined the efficacy of bisoprolol in comparison with sustained release nifedipine [23]. The study included 330 patients who underwent at least 3 episodes of myocardial ischemia according to ECG within 48 hours, verified by treadmill test and Holter ECG monitoring prior to randomization. After 4 weeks of treatment with bisoprolol (161 patients) or sustained release nifedipine (169patients) the mean number of ischemic episodes decreased in both groups. In the bisoprolol group (20 mg/day), the number of episodes of myocardial ischemia decreased from 8.1±0.6 to 3.2±0.4; the total duration of myocardial ischemia decreased from 99.3±10.1 to 31.2±5.5 minutes, and the number of ischemic attacks in the morning also significantly decreased. In the bisoprolol group, the number of ischemic episodes decreased by 60% versus 29% in the nifedipine group. In addition, the effect of bisoprolol was around the clock, which reduced the frequency of ischemia in the early morning hours. Patients in whom transient myocardial ischemia was completely eliminated as a result of treatment had a lower risk of death compared with patients in whom ischemic episodes persisted. The authors also noted an increase in heart rate variability during treatment with bisoprolol. At the same time, there was no effect of the retard form of nifedipine (40 mg/day) on this prognostically significant indicator.

As an antihypertensive drug, bisoprolol also occupies a leading position. When compared with other β-blockers in some aspects, there is a significant superiority of bisoprolol. Thus, in a double-blind randomized study BISOMET, it was shown that bisoprolol is comparable to metoprolol in terms of the degree of reduction in blood pressure (BP) at rest, but significantly exceeds its effect on systolic blood pressure and heart rate (HR) during exercise. Thus, bisoprolol proved to be preferable to metoprolol in the treatment of hypertension, especially in patients with hypersympathicotonia [24].

The BIMS study compared the antihypertensive efficacy of bisoprolol and atenolol in smokers. Bisoprolol and atenolol were effective in 80 and 52% of cases, respectively [25].

It is also important to note that in a comparative randomized 6-month study, bisoprolol at a dose of 10-20 mg / day. caused a significant decrease in the mass index of the left ventricular myocardium by 11%, which is comparable to the effect of angiotensin-converting enzyme inhibitors (enalapril at a dose of 20–40 mg/day) [26].

In a prospective multicenter study, the effect of bisoprolol monotherapy was studied in 2012 patients [27]. In 76%, the target value of diastolic blood pressure (less than 95 mm Hg) was achieved using bisoprolol monotherapy at a dose of 5 mg per day. For the rest of the patients, the dose was increased to 10 mg, which made it possible to achieve the target blood pressure in total in 94% of patients. The long-term efficacy of bisoprolol in hypertension has also been proven in a study involving 1002 patients [28]. In previous studies, the treatment of hypertension with β-blockers was associated with improved long-term prognosis, including reduced mortality, risk of stroke and heart failure [29]. According to the results of the study STOP-Hypertension, in the group of patients treated with β-blockers, overall mortality and sudden cardiac death was less than in the placebo group [30]. In more recent studies, b-blockers have been found to be equally effective in reducing blood pressure and cardiovascular risk in comparison with calcium antagonists and ACE inhibitors.

Almost all researchers note the good tolerance of bisoprolol [31], incl. with a combination of arterial hypertension with diabetes mellitus and chronic obstructive pulmonary disease. The ability to take the drug once a day contributes to a higher adherence of patients to treatment, which is especially important in our country, and an improvement in the quality of life. In arterial hypertension, bisoprolol can be used not only as monotherapy, but also in combination with other antihypertensive drugs.

Thus, bisoprolol, according to the results of numerous comparative controlled clinical trials, has shown its comparability in terms of hypotensive action with other β-blockers, such as atenolol, metoprolol and nebivolol [31–33], and in some cases even superiority.

Actavis bisoprolol is presented on the Russian pharmaceutical market – Cordinorm , produced in tablets of 5 and 10 mg, the use of this drug is the most preferable both from an economic point of view, but also in terms of the quality of the drug.

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