Sartans and modern views on nephroprotection.

Almost every doctor encounters arterial hypertension in his daily activities. This fact cannot but be alarming, since this pathology is associated with a high risk of cardiovascular disasters (myocardial infarction, intracerebral hemorrhage), which leads to significant socio-economic and demographic losses. The goal of modern cardiology is to select the optimal means for correcting blood pressure. Sartans for arterial hypertension effectively cope with the task.

Pharmacodynamics of a group of drugs

The increase in blood pressure occurs due to the release of angiotensin 2 (AT 2). When it acts on the receptors, the vascular wall of the arteries contracts, causing a narrowing of the lumen. This leads to an increase in blood pressure. Taking angiotensin receptor blockers (ARBs) interferes with this action.

The effect of the drug occurs due to blocking of receptors, which is why AT 2 does not act.

There are other therapeutic effects aimed at improving the patient's well-being. They are taken into account when prescribing the type of medicine. The data is presented in the table.

Favorable pharmacodynamic effects are observed in people who use sartans for a long time. A single use of the product only stabilizes the pressure. But this is a temporary effect.

Pharmacological effects

The renin-angiotensin system is responsible for blood flow and blood pressure. The functions of this system are to regulate vascular tone, the interaction of the liver, kidneys, adrenal glands, and the volume of fluid released. The enzyme angiotensin 2 constricts blood vessels, which increases blood pressure.

The group of sartans protects cells from the action of angiotensin 2. The drugs block the production of the enzyme, thereby protecting the walls of blood vessels. The vessels remain dilated, and the pressure does not rise.

Sartans not only have antihypertensive properties, but are also effectively used to treat renal disorders and abnormalities of the heart.

Sartans are one of the groups of drugs for the treatment of hypertension

The therapeutic effects of sartan drugs are reflected in the table.

Scheme describing the mechanism of action of sartans

Drug names

Each group of drugs and its representative differ in chemical structure. They have indications for use, contraindications, and side effects. Therefore, before prescribing a medication, a medical history is first collected and instrumental and laboratory examinations are performed. The following groups and related drugs are distinguished.

1. Biphenyl tetrazole derivatives. Valsartan, Irbesartan, Losartan, Candesartan.
2. Non-biphenyl tetrazole derivatives. Eprosartan or Teveten.
3. Biphenyl non-tetrazole compounds. Telmisartan, olmesartan.

Different chemical compounds of drugs are similar in their mechanism of action. That is, the groups have a similar effect on the adrenal hormone. Based on their effect on AT 2, the following drugs are distinguished:

• competitive - block receptors, displacing the hormonal substance from the complex (Eprosartan, Losartan);
• non-competitive - do not displace the hormonal substance, so the effect on the body lasts for a long time (Telmisartan, Valsartan, Candesartan).

In terms of its effect on receptors and vascular tissue, the drug differs from ACE inhibitors. However, the indications for use are identical. Therefore, sartans are often prescribed to patients who have developed resistance to pril (Enalapril).

Division by generation

There are 2 generations, each of which includes a list of medications. Their division is based on the quality of receptor blocking. The data is described in the table.

Groups of 1st and 2nd generations are similar in blood pressure regulation. Their difference is insignificant and cannot be detected using instrumental examinations. If the patient does not have diabetes mellitus or atherosclerosis, a 1st generation drug is preferable.

It is often impossible to find the main name of the drug in a pharmacy. However, there are trade names that correspond in chemical composition and mechanism of action. The following classification of medicines is distinguished:

• Valsartan: Valsacor, Tareg;
• Losartan: Bloktran, Zisacar, Lozap, Larista, Renicard;
• Irbesartan: Aprovel, Firmasta;
• Candesartan: Angiakand, Giposart, Candecor, Ordiss;
• Olmesartan: Cardosal.

If a patient has side effects to one of the prescribed drugs, it is prohibited to independently replace it with another substance. Complications arise. This makes you feel worse and leads to an excessive decrease in blood pressure.

Areas of use

The main indication for use is stable arterial hypertension. The product also regulates other deviations of internal organs. Therefore, it is additionally recommended for patients suffering from the following conditions and diseases:

• heart failure, left ventricular hypertrophy, replacement of the myocardium with connective tissue after a heart attack, atrial fibrillation;
• proteinuria, renal failure, nephritis;
• diabetes mellitus, hyperglycemia;
• metabolic syndrome;
• atherosclerosis.

The advantage of ARBs is the possibility of combined use with other antihypertensive drugs. The combination with Amlodipine showed effectiveness. If you use only 1 type of drug, the success of therapy decreases. When 2 or more drugs are combined, the patient’s well-being is stable, improvements occur in the heart, kidneys, blood vessels, and brain.

The result of therapy does not appear immediately; it is formed with a long course of use of the prescribed drug.

If diabetes mellitus, atherosclerosis and other diseases are observed, but the blood pressure is normal, it is prohibited to prescribe sartans. Systemic hypotension and sudden syncope will occur.

The only drug from the sartan group approved for post-myocardial infarction is Valsartan. It is prescribed 3 days after a heart attack, but in the absence of the risk of a sudden drop in blood pressure.

Contraindications

New sartans should not be prescribed for:

• increased susceptibility to the components of the drug;
• gestation;
• natural breastfeeding.

Doctors advise women of childbearing age to think about reliable methods of contraception to prevent pregnancy. If pregnancy occurs, you must stop taking the pills.

The safest medications are prescribed with extreme caution in the following cases:

• childhood;
• decreased circulating blood volume;
• bilateral renal artery stenosis;
• kidney failure;
• liver dysfunction, cirrhosis;
• blockage of the bile ducts;
• when taking potassium-sparing drugs.

Advantages and side effects

Cardiologists often prescribe sartans because of the immediate effect and beneficial effect on internal organs. The drugs have the following positive aspects:

• a small number of contraindications;
• The recommended dose of tablets is taken once a day and is slowly eliminated from the body;
• side effects develop in a small percentage of patients, they are reversible with dose adjustment;
• Possibility of reception for elderly people;
• no side effects such as cough caused by ACE inhibitors;
• reducing mortality, improving living standards;
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• reducing the risk of heart attack and stroke;
• absence of development of malignant neoplasms in lung tissue.

Side effects are rare. There is no negative effect on the entire body. Slight dizziness caused by a decrease in blood pressure is possible. If the condition develops frequently, doctors adjust the dosage of the tablets. Side effects are eliminated.

Advantages of the sartan group

The main benefits of taking angiotensin 2 receptor antagonists:

• almost complete absence of contraindications;
• It is enough to take a long-acting drug once a day to lower blood pressure for a day;
• the likelihood of developing adverse reactions is minimal;
• drugs are prescribed for diabetes, in old age, and for impaired renal function;
• do not cause cough;
• increase the life expectancy of patients with disorders of the heart and blood vessels by several years;
• reduce the likelihood of developing cerebrovascular accidents;
• do not provoke the development of lung cancer.

Contraindications for use

The medicine has been tested on different categories of patients. Its quality has been confirmed by pharmacologists. After the data received, it was revealed that it is prohibited for use by the following groups of people:

• hypersensitivity, intolerance to 1 of the components of the composition;
• pregnancy, breastfeeding.

The active substance penetrates the placental barrier and into breast milk, affecting the fetus and newborn. Possible slowdown in development and dysfunction of internal organs. If an unplanned conception occurs, stop taking the pills.

There is a group of patients to whom the drug can be used, but with caution. The doctor regulates the dosage, so the risk of negative effects is eliminated. Control of the number of tablets is indicated for patients with the following conditions:

• minors under 18 years of age;
• the total volume of circulating blood is below the norm for gender;
• renal failure in the stage of decompensation;
• cirrhosis, malignant degeneration of the liver;
• cholelithiasis, other pathologies leading to blockage of the bile ducts;
• taking medications aimed at preserving potassium in the body.

If at the initial stage of treatment no contraindications were identified, but side effects developed, the drug was immediately discontinued. You will not develop an addiction to it, but complications will arise.

Sartans and modern views on nephroprotection.

Oksana Mikhailovna Drapkina , professor, doctor of medical sciences:

– Dear colleagues, dear friends, hello! We are starting our XXXV anniversary Internet session. This is the 35th time we are going on air, communicating with you, and getting the results of the communication. I want to say that, as usual, a very interesting program awaits you, which is posted on the website. You can watch who will perform. We are waiting for your questions because we are always working on feedback. You can call us, write to chat, email. Now all the necessary information is on your screen, please write down this information. We welcome your questions, comments, agreements or disagreements.

Today our session is opened by Professor Grigory Pavlovich Arutyunov. Grigory Pavlovich will tell us about sartans and modern views on nephroprotection. Please, Grigory Pavlovich.

Grigory Pavlovich Arutyunov , professor:

- Thanks a lot. I welcome everyone who joined the online session at this early hour. Let's talk today about how to protect your kidney. To know how to protect the kidney, let's try to evaluate what happens to each of us when the kidney becomes involved in the pathological process.

It must be firmly remembered that the red line is the main methodological approach to understanding the cardiac patient. This is a continuous series of events called the cardiac continuum. It begins during the period of intrauterine development, when any event suffered by a pregnant woman: smoking or a viral infection changes the endothelium, and the atherosclerotic process begins to develop. In parallel with the development of the plaque, a number of other organs are affected. Pay attention to the red rectangles at the base of the pyramid - absolutely identical risk factors: metabolic syndrome, smoking, high cholesterol, high low-density lipoprotein levels. But there are two parallel sides of the pyramid - on the one hand, coronary heart disease develops, and on the other hand, there is continuous damage to the kidney from the development of hypertension inside the glomerulus to the appearance of small doses of albumin, a decrease in the glomerular filtration rate.

Thus, in essence, it must be said that absolutely any patient with cardiac pathology has kidney pathology. Who is the main conductor in this process? This is angiotensin II. There is no need to determine the true level of angiotensin II, it is already elevated. We need to remember what he does. First. It increases the synthesis or activity of vasopressin. This means that the volume of circulating blood in absolutely all these patients is changed towards an increase. It changes the level of aldosterone activity and causes fibroblasts to deposit collagen, including in the kidney, which shortens the lifespan of the glomerulus. It activates the sympathetic nervous system. There is mutual influence here. This means that a greater number of heart contractions appears, the smooth flow of plasma through the kidney is disrupted, and the kidney is damaged.

Today, here is the most important structure for the synthesis of angiotensin II. It is generally accepted on a global scale. Let's take a look at it. Where does the pathological process in the kidney start? Angiotensin, an agent synthesized in the liver, meets rhinitis released from the juxtaglomerular apparatus of the kidney, angiotensin II is formed, which is then converted to angiotensin II under the action of angiotensin-converting enzyme. The most important thing is that angiotensin II will bind to AT1 receptors, which determine several processes in the human body. The first thing that will happen is that the smooth muscle cells will hypertrophy, but angiotensin II will cause sodium retention in the ascending limb of the loop of Henle, which will cause an increase in circulating blood volume, and it will primarily cause spasm of the afferent artery, which will lead to the development of intraglomerular hypertension.

Thus, a doctor looking at a cardiac patient must remember that the glomerulus has changed in this patient, a situation has arisen in it that has led to an increase in pressure.

Why are we concerned today about the chemicals that are highlighted in lilac on this slide? Because chymases can convert angiotensinogen to angiotensin II, bypassing the help of angiotensin-converting enzyme. This means that the kidney very quickly becomes an organ that synthesizes its own angiotensin II.

So, if angiotensin II is synthesized, then it necessarily binds to AT1 receptors, the kidney begins to return sodium and water in large quantities, angiotensin II causes a spasm of the arteries, primarily the carrying artery, which radically rearranges the functioning of the glomerulus itself. For an hour, the therapist does not think that the huge number of drugs he uses interfere with the functioning of the reninangiotensin sterone system.

Today we are not talking about beta blockers, which reduce the release of renin from the juxtaglomerular apparatus, nor about spirolactones and mineralocorticoid receptor blockers, which block collagen deposition, including in the kidney itself. We are talking today about angiotensin II receptor antagonists, sartans. That is, of the six classes of drugs that affect the reninangiotensin sterone system, we are talking today about one - the drugs sartans, which block this work. To understand what we influence, let's look at what happens in the kidney several years after the onset of cardiovascular disease.

The first thing in front of you is a lifetime kidney biopsy. This is what the kidney looks like at the onset of arterial hypertension. Look. So in six to eight years. So in ten to eleven years. So after 14 years. Instead of a glomerulus, only a sclerotically changed area of ​​the kidney remains.

Thus, the first process that proceeds inexorably is the development of fibrosis of the kidney itself. The second process is very important for the therapist, and this is where he intervenes very quickly. Pay attention to the number 5 and 1. Number 1 is the afferent artery. Its diameter is exactly twice as wide as the diameter of the afferent artery (number 5). This means that the blood that has passed into the glomerulus encounters slight resistance to leave the glomerulus, and this pressure gradient, which occurs on the narrower afferent artery, is sufficient for urine to begin to be filtered.

What is urine filtered through? You see a thin layer of white cells - these are podocyte stalks surrounding the glomerulus. Podocyte feet have an electrical charge. Imagine a patient with high levels of angiotensin II, he compressed the artery. This means that the blood came through artery 1, but cannot or has difficulty leaving through the entraining artery, which means that the glomerular loops are filled with blood. These overfilled loops begin to put pressure on the podocyte feet, modifying the electrostatic charge, and the electrostatic charge is equal to the charge of the albumin molecule.

Look how delicately everything is arranged. The charge drops, albumin ceases to be repelled and falls into the primary urine in large quantities. The therapist will detect this process by the definition of microalbuminuria (albeit an outdated term now), by small doses of albumin or low-grade albumin in the urine. Thus, the appearance of albumin in the urine for the therapist means that there is very high pressure in the glomerulus. This was the second process from which it was necessary to protect.

The third process is excess blood flow through the kidney. If one glomerulus dies, then the blood that should have come to this glomerulus ends up in the adjacent glomeruli; they are not ready to accept such blood flow.

Finally, one of the most terrible events is that if the angiotensin II carrying artery is compressed, this means that less blood enters the tubulointerstitial tissue. How will the therapist see tubulointerstitial tissue ischemia? If there is ischemia, then there is an uncontrolled return of sodium. Uncontrolled sodium return is a modification of the rigidity of the vascular wall. This means that the nighttime pressure profile in these people tends to change. They go from dippers to non-dippers or even nightpickers.

These simple observations of life and measuring blood pressure in their patients allow therapists to tell how the kidney has changed. Local ischemia undoubtedly has a very negative impact on the patient’s life, because the process of sclerosis of the second structure of the kidney—tubulointerstitial tissue—begins. Finally, all this ends in absolute oligonephronia. Oligonephronia means a decrease in the number of glomeruli.

Let me remind you that every person is born with approximately a million glomeruli in each kidney. If the weight at birth is as expected, then this is true, but if the weight is a kilogram less, he loses approximately 250,000 glomeruli. Thus, when collecting anamnesis, the therapist must already guess which kidney his patient initially has, and how quickly he needs to intervene. After all, a smaller number of nephrons suggests a completely early process of inclusion of the kidney in this pathological process.

So, we firmly understand that angiotensin II, which comes from the outside, angiotensin II, which is synthesized directly in the kidney, forever modifies the functioning of the glomerulus, tubulointerstitial tissue, and forever increases the return of sodium to the body. This means that the pressure itself changes in our patients.

Look at the red lines. The red lines are collagen that has been deposited in the glomerulus. This glomerulus is doomed, but instead of the dead glomerulus a new one will not grow, there will be connective tissue there, and the blood that should have come to this glomerulus will flow around the glomerulus and enter other glomeruli, creating hyperfiltration there, leading to the rapid death of these glomeruli.

So, we have decided on the most important pathological things. How will the therapist see all this? He should look for some changes. The most important change that a therapist will see when analyzing his patient’s kidney is a decrease in glomerular filtration rate.

Here are several formulas that any therapist should know. They allow you to calculate the glomerular filtration rate directly at the appointment. Before us is the Cockcroft–Gault formula. Despite all its conventionality, it allows one to know the glomerular filtration rate in real clinical practice. Here is the MDRD formula, which stands for “modified kidney disease diet.” In this large study, this formula was derived. It requires a calculator, but it will allow the doctor, especially the therapist, to figure out how far the changes in the kidney have gone.

One of the most accurate formulas today is a formula called chronic kidney disease. A collaboration of epidemiologists that developed this formula, requiring knowledge of creatinine levels to calculate it. Pay attention to the unit of measurement. Here creatinine is measured in milligrams per deciliter. In Russia, another unit of measurement is adopted - micromol per liter. We must remember that one milligram is 88.6 micromol per liter. This will allow you to easily calculate the glomerular filtration rate for each patient.

Let's look at a modern analysis of how the kidney loses protein. We abandon the concept of “microalbuminuria”, since microalbuminuria starts at 30 mg per 24 hours. You can clearly see that the optimal level is less than 10 mg in 24 hours. Microalbuminuria, which we talked about then, is insignificant doses, in fact it is a high level of protein being lost. The therapist will be able to understand very early that his patient has a changed kidney.

Look, a changed kidney begins for a therapist in his professional consciousness with a glomerular filtration rate below 60. We must remember the great doctors of the world who walked towards this understanding. Undoubtedly, this is Bright. Doctors of the older generation remember this name when they said Bright's disease instead of glomerulonephritis. It was Bright who first described changes in the kidney associated with changes in the heart.

This is the great Russian doctor Tingerstedt. He was the first in the world to discover renin and describe subsequent events. This is the great American doctor Franz Volhard, who introduced the concept of target organs. The kidney was the first to be described by him as an organ that changes the glomeruli.

Of course, these are outstanding Soviet doctors who left their mark on the world. First of all, Evgeny Mikhailovich Toreev, who described the stages of kidney changes in these processes. I want us to feel that pride that allows us to have special respect for Russian clinical thought, which developed the concept of kidney change.

How do we relate kidney change in the context of cardiovascular disease today? First of all, we say that there are two special connections for the therapist. Any chronic cardiac pathology modifies the condition of the kidney. Any chronic kidney pathology modifies the state of the myocardium.

Understanding what happened, let's look at where and at what stages sartana is included in this process. Let me remind you that sartans block AT1 receptors. This means that they don’t care where angiotensin II came from - it was synthesized by chymases or angiotensin-converting enzyme on the receptor that perceives it - angiotensin II is blocked. We must treat all sartans with respect. All sartans have undergone major studies. Therefore, it is unacceptable for a therapist to say good or bad sartan. Let's look at the niches where these sartans were tested.

The first study that was historically performed was the losartan study. These were patients with severe kidney damage and diabetes mellitus. They had high levels of creatinine, high levels of lost albumin. Losartan has proven its ability to block the rate of doubling of creatinine levels - the most important parameter for a therapist. He must consider the rate at which the level of creatinine in the blood increases, and when it approaches a factor of two, this is an extremely negative prognosis. And it has been proven in renaal studies to slow down or reduce the amount of protein lost. This means that at the last stages, during pronounced changes in the kidney, losartan has proven its effectiveness.

Look at the drug "Irbesartan", which has proven its dose-dependent effect in the early stages of the disease (...) (00:14:51) and in the later stages of the disease it has proven its superiority over the calcium antagonist in protecting the kidney, but most importantly, it has proven its effect in the early and late stages of treatment of kidney pathology. It is very important for us that almost all sartans have proven this effect. We know that it is possible to combine sartan and an ACE inhibitor. This has been proven in studies by Caln. There, candesartan was combined with lisinopril and showed a greater reduction in the level of lost protein. This is not a very common technology today.

As a rule, it is believed that if your patient has more than a gram of protein, and you cannot adequately reduce the level of protein lost on monotherapy, you can combine this process. But the most important thing for us is that all sartans, I’m talking about the last one, are valsartan, which has proven its effect in the initial stages, not even sartan, but simply the diuretic drug “Indapamide” has proven its effectiveness in patients with diabetes, reducing the amount of protein lost.

It is very important for us to understand that behind all this there is a question: who is more effective? Calcium antagonists or sartans? Sartans. Who is more effective: inhibitors or sartans? They have proven to be equally influential. What do we know for sure? For us, the most important parameter is the level of the number of patients with adequate average pressure achieved.

Look at the MDRD study, it answered a key question for the therapist: what target pressure should be maintained to reduce the amount of protein lost. You see very well in these patients that strict control and not very strict control have shown that you are under strict control, but without going too far, I ask you to hear this word, without lowering the pressure excessively, you reduce the amount of protein lost in your patients. So, to date, all sartans have proven their effectiveness in patients with the disease.

Let's look at the stage before the development of the disease. And here only one sartan has undergone clinical trials to date. This is the stage when there is no microalbuminuria yet. The stage in which the therapist can ask the question: I have diabetes mellitus, but no microalbuminuria, can I apply technology that will slow down the process of occurrence (an almost obligatory process) of microalbuminuria? For such a technology, for such a formulation of the question, the ROADMAP study was created at one time and olmesartan, which, unfortunately, is little known in our country, passed this clinical trial.

Let's remember the basic things that have been accumulated in these studies. First, the concept of basic drugs was introduced in patients with low glomerular velocity - chronic kidney disease. For three months the rate is below 60 – you have the right to think about chronic kidney disease. We know for sure: ACE inhibitors or sartans should be prescribed to such patients even with normal blood pressure, if their level of albumin loss is higher than 30 mg per 24 hours.

Second approach. We must firmly remember that if the rate is below 60, sartans or inhibitors are the drugs of choice, because they are the main therapy in the treatment of such patients.

Let's say the most important thing. Losartan reduced the doubling level of creatinine and reduced the level of lost protein. Valsartan turned out to be highly effective in the initial stages and outperformed the calcium antagonist. For us, irbesartan turned out to be effective at the beginning and end of the disease, reducing the amount of protein released, and proved especially important in the terminal stages of the disease.

Let me draw attention to the drug olmesartan, which is unfortunately little known in Russia. Olmesartan came into medicine, into the clinic of internal medicine, in its comparison with ACE inhibitors in elderly patients. Let's remember the peculiarity of the vascular bed in elderly patients. These are people with a very high tone of the peripheral arteries, with a high speed of pulse wave movement. Olmesartan titrated (note the second keyword “titrated”) from 10 mg to 40 mg was very effective in older people because it lowered blood pressure, and most importantly, at night, preventing older people from increasing blood pressure in the early morning hours , which is considered today as a very dangerous moment - a precursor to a possible cerebral hemorrhage or sudden death. And first of all, it has proven its effectiveness on altered vascular walls, the ability to achieve the target pressure in a large percentage of cases.

For us, the most important issue is the speed of reaching target blood pressure levels. Almost the absolute majority of patients reached this stage in the range of 8–12 weeks. Thus, we are talking about the effective effect of olmesartan, sartan on the vascular bed with an initially altered morphological structure.

Going back to the ROADMAP study, we understand that the drug that was used in this study had a very good testing base prior to this study, and we knew that it was a powerful antihypertensive drug. The ROADMAP study has grown into a huge number of stories and rumors. Let's understand this study without emotion. Approximately 4,500 patients are included in this study. These are patients who have diabetes mellitus, from 19 European countries, but they do not have the most important thing - these patients do not now have microalbuminuria and they have a good glomerular filtration rate, which is clearly above 60, they have 85 ml per minute. So, patients with diabetes before the development of diabetic nephropathy, before the development of an altered glomerulus, before the development and appearance of microalbuminuria are included in this study.

Please note the key point, I have spoken several times today about the need to titrate olmesartan. The study I talked about about the hypotensive effect was titrated there, but not titrated here. And this is probably one of the main mistakes in this study. Forty milligrams of olmesartan was prescribed as a base, starting dosage. So, forty milligrams of olmesartan in patients with diabetes mellitus without microalbuminuria versus the same basic therapy that they receive in this line of research, just a placebo in relation to olmesartan. What was the goal?

Let's measure the time it takes on olmesartan therapy before microalbuminuria develops. If we can slow down this time and lengthen it, then we can say for sure that the drug definitely acts as a nephroprotector. Let's say the most important thing, on top of the basic treatment, all patients with diabetes receive 40 mg at once. And finally look at the purple part of the slide. What is the target level stated in this study? Less than 130/80 mm Hg. Art. I ask your attention especially to the blood pressure numbers. This is the most important parameter in this study.

So, this research begins, and the primary point (I emphasize again) for the first time in history was proclaimed: “We are treating patients without the disease, we are trying to delay the onset of the disease - the appearance of microalbuminuria.” Look at the top line, it shows the number of patients with coronary heart disease. It would seem like a one percent difference, but one percent when the study included 4,500 patients is a big number. Unfortunately, as a result of special randomization, the number of patients was one percent greater in the olmesartan group than in the placebo group.

Now look at the main result of the study. It was possible to significantly reduce the onset of microalbuminuria. This is a very important question. The time to onset of microalbuminuria differed from the placebo group by 23%. This is a very important success for us. We understand that we now have a drug in our arsenal that can prevent the development of the disease. Placebo and olmesartan can be read on this graph. The olmesartan curve is significantly lower than the placebo curve. This means that we have slowed down the process of kidney destruction. So, we got the most important answer in this study. We have proven that the use of olmesartan leads to a slowdown in changes in the structure of the kidney, slowing down the time when the changed glomerulus will accurately manifest its pathological activity by loss of protein. So, we extended that bright period of the patient’s life, which passed without microalbuminuria.

Experts came to the conclusion that today we can say with all confidence and responsibility: olmesartan is currently the only sartan that, from the point of view of evidence-based medicine, has proven its effectiveness as a true nephroprotective drug. I will emphasize that the sartans used before also proved their nephroprotection, but they worked at the “disease” stage, and olmesartan worked at the “pre-protein loss” stage, “pre-disease” in fact.

Let's get back to the tricky side of this study. These are pressure levels. You can see very clearly that the systolic and diastolic pressures differed between the groups, and they differed significantly. This difference resulted in three millimeters for systolic and two millimeters for diastolic pressure. More than 80% of patients lowered their blood pressure below 130/80. Now look at the results. The main thing we find is that overall mortality is similar in the two groups. Cardiovascular mortality is the same. But there is a difference that the vast majority of people have focused on. Let's understand it, it taught us a lot.

So, going into the differences between groups, let’s focus on the main thing that unites them. The groups did not differ in terms of all-cause mortality and cardiovascular mortality, but they did differ in the number of fatal myocardial infarctions that occurred in these groups. Note 11 events compared to one in the placebo group. Why might this happen? This requires explanation, and it teaches the therapist great attention to blood pressure levels. The first thing we will say is that there were more patients with coronary heart disease. A pressure drop lower than 130/80 is not best for these patients. Second. We draw the therapists' attention to the target pressure level. If you lower your blood pressure below 130/80, especially below 120, you need to understand that this is not the best thing you can do for your patients who have significant coronary artery disease.

So, the ROADMAP study showed us olmesartan - a powerful antihypertensive drug that requires careful treatment, requiring mandatory titration and monitoring of blood pressure levels by a therapist. Reducing blood pressure may worsen the course of the disease in patients with underlying coronary heart disease, but with all this we must remember that this is the only sartan that has proven effective in preventing further kidney destruction and the appearance of microalbuminuria.

I draw your attention to this curve of yellow bars. You see that at a pressure of 160 and at a pressure lower than 120, the amplitude of the yellow bars is approximately the same. This means for the therapist to be overly attentive to the level of blood pressure that he creates in his patient. A pressure drop lower than 120 will have an extremely negative impact on the course of coronary heart disease in cases of severe coronary heart disease in your patients. Therefore, remembering the power of the drug, remember also about safety.

The experts' explanation today for why this ratio of death from myocardial infarction was so different between the placebo group was not the purpose of the study at all, it was an incidental finding in this study. In the placebo group and in the main drug group, the main explanation was the lack of physician control over the blood pressure levels in these patients.

I would like to draw your attention to a purely therapeutic approach to the management of such patients. When you have selected a patient for sartan treatment and started sartan therapy, the therapist must remember that the effect of sartan depends on the amount of salt his patient eats, so he controls the food diary as a therapist, he controls what his patient eats. If the rate is lower than 30, he controls the amount of protein eaten, because more protein causes hyperfiltration and impairs glomerular function, so he calculates the diet.

This is a separate lecture on the amount of protein at 0.6–0.8 grams of protein per kilogram of weight. Imagine that a patient weighing 60 kg must eat 36 grams of protein per day. Let every therapist now ask himself a question: does he know how to calculate such a diet? Will he not speak general words to his patient or his wife, who will be in very difficult conditions? But he must control the amount of protein eaten, the amount of salt eaten.

The third aspect that he must monitor throughout his patients is the dose of the starting drug. You see in the column farthest away from you, with a glomerular filtration rate of 10 to 30 ml per minute per 1.73 m2 (this is the area of ​​our body), control of the starting dose is required in several situations. For candesartan, the dose is reduced by half; for olmesartan, the dose in these situations should be reduced, at least titration should begin with a dose of 10 mg, which will avoid negative aspects.

So, knowledge of three auxiliary things: salt, protein and starting dose - allows us to make therapy with sartans highly effective, lasting as long as possible in our patients and the most effective nephroprotective aspect of treatment. Thank you for your attention.

Drug interactions

The ARB group of drugs is prescribed with other drugs, since they rarely enter into chemical interactions without interfering with the therapeutic effect. It is recommended to take it together with other medications aimed at improving the patient’s well-being with cardiovascular pathologies and diabetes.

However, when selecting the dosage, it is taken into account that when combining antihypertensive substances, the pressure will decrease even more. To eliminate the risk of systemic hypotension and syncope, adjust the dose of both drugs used.

There is a group of drugs that can change the condition of the cardiovascular system, liver, and kidneys when combined with sartans. The risk of this action is minimal, but periodic laboratory tests of blood and urine are required. Such means include:

• non-steroidal anti-inflammatory drugs;

• diuretics with no potassium removal effect;
• anticoagulants;
• medicines containing potassium.

These medications may cause side effects. For example, if you take Heparin along with Valsartan, the blood will become excessively thin. The patient may experience sudden bleeding from minor bruises.

Is it possible to develop malignant neoplasms?

Some medications aimed at lowering blood pressure cause the development of malignant tumors. Cancer usually forms in the lung tissue. The first sign of pathology is the presence of a cough. This is a side effect that occurs with ACE inhibitors. Therefore, it is difficult to recognize a complication or cancer in the early stages.

Studies have been conducted to determine the presence or absence of cell malignancy when using sartans. The following recent research findings have been identified:

• absence of the slightest percentage of development of malignant cells;
• reducing the risk of neoplasms of a benign or malignant nature.

Research on cancer is still not closed. Some antihypertensive drugs have this effect. The risks of cancer are minimal. If a patient with arterial hypertension does not take medications, there is a possibility of a heart attack or stroke. When using ARBs, people's lives are prolonged and their quality is improved.

Drug compatibility

Sartans interact well with other types of drugs without causing negative reactions. Sartans can be taken with any means for the treatment of heart and vascular diseases, diabetes. The drugs significantly reduce blood pressure, so it is necessary to control the dosage during complex therapy with other antihypertensive drugs.

Particular caution should be taken when taking tablets in combination with:

• NSAIDs: Ibuprofen, Nimesulide;
• potassium-sparing diuretics;
• heparin;
• potassium-containing drugs.

Comparison with ACE inhibitors

ARBs or ACE inhibitors have similar mechanisms of action of active substances on the body. But ACEI affects the conversion of angiotensin 1 to angiotensin 2. This prevents its effect on vascular endothelial receptors. Later it was discovered that it was possible to eliminate not only this reaction, but also the direct effect of the hormonal substance on the cells. This enhances the hypotensive effect and improves a person’s well-being faster.

There are other types of receptors that cause increased blood pressure. Sartans do not affect them. Therefore, these drugs will not completely eliminate the use of ACE inhibitors.

ACE inhibitors remain the drugs of choice at the initial stage of identified hypertension.

In terms of the degree of reduction in blood pressure, both drugs have a similar effect.

Angiotensin receptor blockers are used for patients who have a dry cough. With its long-term formation, an exhausting condition occurs and a headache develops.

If a person does not have a cough, it is better to use an ACE inhibitor.

ARBs are considered best if the patient develops not only hypertension, but also other diseases. For example, diabetes mellitus, atherosclerosis, renal failure. Since these are new drugs, their effect on the body has not been fully studied. This is especially true for patients who have been using pills for many years.

Effect of ARBs on patients at risk of myocardial infarction

The only drug from the ARB group whose effectiveness has been proven in myocardial infarction is Valsartan. It is prescribed from day 3 after a heart attack, but in the absence of a risk of hypotension. If there is one, the time is extended to 10 days.

Researchers believe that other drugs can cause circulatory problems in the myocardium. This will cause a sudden drug-induced heart attack. However, this theory remains unproven.

Due to the availability of such data, studies were conducted. The results were contradictory. Some patients develop a heart attack, others do not. Therefore, it is believed that the risk of heart attack is present, but it is negligibly small. More often it develops in patients who neglect the rules of a healthy lifestyle:

• smoking;
• frequent drinking of alcoholic beverages, alcoholism;
• taking chemicals, drugs;
• eating fatty, fried, spicy, smoked, salty foods.

Scientists who consider sartans to be the drugs of choice for hypertension explain that a heart attack is not caused by the medicine, but by an incorrect lifestyle. For example, in case of violation of the ban on bed rest, physical overload. Other researchers make reasonable arguments that the incidence of heart attacks increases with ARB use. Therefore, the question is considered open and unproven.

The essence of treatment with ARBs

Angiotensin receptor blockers are medications that significantly improve the quality of life of a patient with arterial hypertension. Blood pressure decreases, and a normal state of systemic blood flow is formed. The drug can be used not only as a monotherapy, but also in combination with other drugs. The possibility of side effects and negative drug interactions is extremely low.

The advantage of the product is in a small dosage used per day. 1 tablet in the prescribed dose is enough to have an effect. This is due to prolonged metabolism in the liver and excretion by the kidneys. If hypertension occurs due to diabetes mellitus or atherosclerosis, the disease will be controlled, so repeated surges in blood pressure will not occur.

Possible adverse reactions

Sartans are considered to be the safest blood pressure medications. The likelihood of developing side effects of sartans is so small that it is not included in a separate list. In rare cases, blood pressure sartans without side effects can cause dizziness due to a decrease in blood counts. Doctors advise taking pills at night to avoid any discomfort.

A side effect of taking sartans may be dizziness.