Combined antihypertensive therapy: current status. Drug antihypertensive therapy

Data from the decisions of experts of the All-Russian Scientific Society of Cardiology (VNOK) in 2004 on the adoption of target levels blood pressure. A combined regimen of antihypertensive drugs as a tool for normalizing high blood pressure. Analysis of the history and data of ongoing research.

Profequarrel V.S. Zadionchenko, Ph.D. G.G. Shekhyan, N.Yu.Timofeeva, A.M. Shchikota, Ph.D. A.A. Yalymov

MGMSU

Many completed in last years studies have clearly demonstrated that only “strict” control of blood pressure (BP) can reliably reduce the incidence of cardiovascular complications (CVC) - myocardial infarction (MI), acute disorder cerebral circulation(CVA), chronic heart failure (CHF) in patients with arterial hypertension(AG). Taking into account the results of these studies, desirable target blood pressure levels were determined. According to the recommendations of experts from the World Health Organization (WHO) and the International Society arterial hypertension(MOAG) (1999), the target blood pressure level for young and middle-aged people, as well as patients diabetes mellitus(SD) values ​​not exceeding 130/85 mm Hg are recognized. Art., for elderly people – 140/90 mm Hg. Art. In 2003, the European Society of Hypertension (ESH), together with the European Society of Cardiology (ESC), adopted recommendations for the management of patients with hypertension and published the 7th report of the American Joint National Committee (JNC) on the prevention, detection, definition and treatment of high blood pressure . In these documents, values ​​not higher than 140/90 mm Hg are also taken as the target blood pressure level. Art., and for patients with diabetes and kidney damage - no higher than 130/80 mm Hg. Art. In 2004, experts from the All-Russian Scientific Society of Cardiology (VNOK) adopted similar target blood pressure levels.

Achieving target blood pressure levels with the help of one antihypertensive drug (AGD) is possible only in 5–50% of patients with 1st and 2nd degree of severity of hypertension, and in patients with 3rd degree of severity of hypertension, in the presence of target organ damage, diabetes, signs of cardiovascular complications, monotherapy is effective only in in rare cases. Back in 1989, data from the Glasgow Blood Pressure Clinic study confirmed the dominant role of the blood pressure level achieved as a result of treatment in the prognosis of hypertension and clearly demonstrated high performance cardiovascular mortality and morbidity if the degree of its reduction is insufficient. These provisions were later confirmed in the HOT study. Similar data were obtained from a retrospective analysis of most cited studies on hypertension (Fig. 1).

A combined regimen of antihypertensive drugs as a tool for normalizing high blood pressure has always been present in the pharmacotherapeutic arsenal of hypertension, but views on its place combination therapy in the treatment of hypertension were re-examined. If combination therapy is ineffective, they switch to prescribing drugs that are part of the combination used in full dose, or add a third drug in a low dosage. If this therapy does not lead to achieving target blood pressure levels, then a combination of 2-3 drugs is prescribed in the usual effective doses. The question still remains open as to which patients can be prescribed combination therapy at the first stage of treatment.

To make a simpler decision on how to treat a patient with hypertension who comes for an appointment for the first time or repeatedly, we suggest doctors use the algorithm presented in Figure 2.

Even if the patient comes for the first time, we have the opportunity to measure blood pressure and preliminary assess the degree of cardiovascular risk. If the risk is low or moderate, we can start with recommendations regarding lifestyle changes and the yellow side of the algorithm; if the risk is high or very high, it is necessary to prescribe immediately drug treatment, walking along the red side. The advantage of the algorithm is that, by helping to quickly make a decision, it leaves the doctor complete freedom of choice in the treatment of a patient with hypertension.

Historical reference

Back at the beginning of the 20th century. it became known about the influence of neurohumoral factors on the development of hypertension. In the 1930s a substance that is now called angiotensin II was discovered. In the 1950s it was proven that it directly stimulates the synthesis of aldosterone, and 10 years later the role of angiotensin-converting enzyme (ACE) in the neurohumoral regulation of blood pressure was studied, and the concept of the functioning of the renin-angiotensin-aldosterone system (RAAS) was formulated. The search began for substances that could act at this level. The first drug, an angiotensin II receptor antagonist, was synthesized in 1969, it was saralazine. The drug had a powerful, but extremely poorly predicted antihypertensive effect; at the same dose, it could cause collapse or, conversely, lead to sharp growth HELL.

Despite the failure, work in this direction continued, and in 1971 the world's first ACE inhibitor, teprotide, was synthesized. The history of its creation is interesting: in 1965, the Brazilian scientist Ferreira, while studying rattlesnake venom, discovered its ability to stabilize bradykinin. The drug, isolated from snake venom, was used for a very short time in clinical practice. The reasons for this were the high toxicity of the drug, the short duration of the effect and the need for intravenous administration.

Continued research into the mechanism of functioning of the RAAS led to the creation of the first tableted ACE inhibitor, captopril, in 1975. This was a revolutionary discovery that began new era in the treatment of hypertension and heart failure.

In 1980, Merck employees synthesized enalapril. Duration of his clinical the effect lasted for about 12–24 hours. The drug has been actively used in clinical practice for several decades and continues to be effective means blood pressure control.

Diuretics are the oldest class of antihypertensive drugs, their use dates back to the 1950s. (Table 1). Despite the active introduction of new classes of antihypertensive drugs, primarily calcium antagonists and ACE inhibitors, interest in the diuretic class has not diminished. Firstly, in modern large clinical studies In the field of hypertensiology, a thiazide diuretic is usually used as a standard reference drug with proven effectiveness. Secondly, in modern international recommendations for hypertension, a diuretic is a mandatory component of combination antihypertensive therapy, which has already been used in initial stage treatment of patients with hypertension. Thirdly, the tactics of using diuretics for long-term treatment AG to improve long-term safety.

The first fixed combinations of antihypertensive drugs (reserpine + hydralazine + hydrochlorothiazide; α-methyldopa + hydrochlorothiazide; hydrochlorothiazide + potassium-sparing diuretics) appeared in the early 1960s. In the 1970s and 1980s. The leading place was taken by combinations of a diuretic, usually in a high dose, with β-blockers or centrally acting drugs. However, soon, due to the emergence of new classes of drugs, the popularity of combination therapy decreased significantly. It was replaced by the tactics of differentiated selection of drugs using them in maximum doses in monotherapy mode.

Monotherapy high doses antihypertensive drugs often led to the activation of counter-regulatory mechanisms that increase blood pressure and/or the development of adverse events. In this regard, it is not surprising that in the next decade hopes for a higher antihypertensive activity of ACE inhibitors did not materialize, and the pendulum of attitudes towards combination therapy returned to its original position, i.e. it was recognized as necessary for most patients with hypertension.

At the end of the 1990s. Fixed low-dose combinations of antihypertensive drugs have appeared: not containing a diuretic (calcium antagonist + ACE inhibitor; dihydropyridine calcium antagonist + β-blocker) or containing it in low doses. Already in 1997, the list of antihypertensive drugs in the report of the US Joint National Committee included 29 fixed combinations. The feasibility of low-dose combination rational antihypertensive therapy, especially in patients with high risk development of cardiovascular complications, was confirmed in the latest recommendations of WHO / International Society of Arterial Hypertension (1999) and DAG-1 (2000).

Rational combination therapy must meet a number of mandatory conditions, such as:

safety and effectiveness of components;

the contribution of each of them to the expected result;

different but complementary mechanisms of action;

more high efficiency compared with monotherapy with each component; balance of components in terms of bioavailability and duration of action; strengthening organoprotective properties;

impact on the universal (most common) mechanisms of blood pressure increase;

reduction in the number of adverse events and improved tolerability.

Table 2 shows undesirable consequences the use of the main classes of drugs and the possibility of their elimination by adding a second drug.

Combination drugs consisting of an ACE inhibitor and a thiazide diuretic, long time are used in clinical practice and are currently one of the most commonly used groups of drugs for the treatment of hypertension, heart failure and coronary disease heart (CHD). In the pathogenesis of these conditions important role plays the activation of two neurohumoral systems of the body: the RAAS and the sympathoadrenal (SAS). The activation process is caused by such unfavorable factors as a decrease in cardiac output, organ ischemia, loss of sodium and water, significant change in pH, etc. As a result, the formation of angiotensin II occurs– biologically active substance, which is a powerful vasoconstrictor, stimulates the release of aldosterone, and also increases the activity of the SAS (stimulates the release of norepinephrine). Norepinephrine, in turn, can activate the RAAS (stimulates renin synthesis).

Ultimately, an increase in the activity of these two body systems, causing powerful vasoconstriction, an increase in heart rate, cardiac output, maintains circulatory function at an optimal level, and maintains homeostasis of the body. Normally, the activation of the body’s pressor systems (RAAS and SAS) is “opposed” by the action of the depressor system (kallikrein-kinin: the key link is bradykinin), causing systemic vasodilation. However, when long-term action various pathological factors described above, normal regulation is disrupted, and as a result the effects of the pressor systems predominate. ACE inhibitors inhibit the effects of pressor systems and simultaneously activate depressor systems.

The main effects of the IAC (enalapril) are due to the blockade of the angiotensin -converting enzyme: the elimination of vasopressor, antidiuretic and anti -natriyuretic action of angiotensin II, increased vasodilator, diuretic and sodium -eater effect of bradykinin and other endogenous vasodilators (prostaglandins J2 and E2, sodium -sodium -sodium -sodium peptite , endothelial factor of relaxation), as well as indirect blockade of SAS activity by inhibiting the synthesis of norepinephrine. The antihypertensive effect of the thiazide diuretic - indapamide is due, on the one hand, to the natriuretic effect, which eliminates the overload of the vascular wall with sodium and reduces its hyperreactivity to various vasopressor agents (catecholamines, angiotensin II, etc.), on the other hand, to the direct vasodilating effect due to the blocking of slow calcium channels in smooth muscle cells of the vascular wall, increasing the synthesis of prostacyclin in vascular wall and prostaglandin E2 (PGE2) in the kidneys and suppression of the synthesis of endothelium-dependent vasoconstrictor factor.

FARmAcokinetics combination drug Enzix ®

Enalapril: after oral administration, about 60% is absorbed from the gastrointestinal tract, the bioavailability of the drug isequals 40%. Enalapril is quickly and completely hydrolyzed in the liver to form activemetabolite - enalaprilat, which is a more active ACE inhibitor than enalapril. Enalaprilat easily passes through histohematic barriers, excluding the blood-brain barrier (BBB), a small amount penetrates the placenta and into breast milk. T1/2 of enalaprilat is about 11 hours. Enalapril is excreted mainly by the kidneys - 60% (20% in the form of enalapril and40% - in the form of enalaprilat), through the intestines - 33% (6% - in the form of enalapril and 27% - in the form of enalaprilat).

Indapamide: after oral administration, it is quickly and completely absorbed from the gastrointestinal tract; bioavailability – 93%. Indapamide passes through histohematic barriers (including placental), penetrates into breast milk, and is metabolized in the liver. T1/2 of the drug - 14-18 hours. 60-80% is excreted by the kidneys in the form of metabolites (unchanged - about 5%), through the intestines - 20%. In patients with chronic renal failure(CRF) pharmacokinetics do not change and do not accumulate.

Rational combination therapy allows one to achieve a good antihypertensive effect, which is combined with excellent tolerability and safety of treatment. Due to the fact that combination therapy is becoming one of the main directions in the treatment of patients with hypertension, fixed combinations of antihypertensive drugs containing two tablets in one tablet have become widespread. medicines. Their use makes it possible to obtain a stable antihypertensive effect with a minimum amount of side effects. Of course, combination therapy is necessary to achieve and maintain the target blood pressure level, but it should be remembered that this therapy means taking at least two medicines, the frequency of assignment of which may be different.

Therefore, the use of drugs in the form of combination therapy must meet the following conditions:

• drugs must have a complementary effect;
• an improvement in the result should be achieved when they are used together;
• Organoprotective properties should be enhanced;
• drugs must have similar pharmacodynamic and pharmacokinetic parameters, which is especially important for fixed combinations.

The use of a combination of two drugs that have similar pharmacodynamic properties may lead to various consequences from the point of view of quantitative parameters of interaction: sensitization (0+1=1.5); additive action (1+1=1.75); summation (1+1=2) and potentiation of the effect (1+1=3). In this regard, it is quite possible to distinguish rational and irrational combinations of antihypertensive drugs (Table 3).

Combination therapy does not always mean an increase in the antihypertensive effect and can lead to an increase in adverse events (Table 4).

The advantages of low-dose combination antihypertensive drugs include the following:

• simplicity and convenience of administration for the patient;
• facilitating dose titration;
• ease of prescribing the drug;
• increasing patient adherence to treatment;
• reducing the frequency of adverse events by reducing doses of components;
• reducing the risk of using irrational combinations; confidence in the optimal and safe dosage regimen; price reduction.

The disadvantages are:

• fixed doses of components;
• difficulties in identifying the cause of adverse events;
• lack of confidence in the need for all components used.

Additional requirements for combination drugs are the absence of unpredictable pharmacokinetic interactions and optimal ratio residual and maximum effects. Rational selection of components creates the prerequisites for prescribing drugs once a day, which in monotherapy have to be used two or even three times a day (some β-blockers, ACE inhibitors and calcium antagonists).

Thiazide diuretic + ACE inhibitor is a highly effective combination that provides an effect on two main pathophysiological mechanism AH: sodium and water retention and activation of the RAAS. The effectiveness of such combinations has been demonstrated in low-, normo-, and high-renin hypertension, including in patients who do not respond to blockers of the renin-angiotensin system (for example, in African-Americans). The frequency of hypertension control increases to 80%. ACE inhibitors eliminate hypokalemia, hypomagnesemia, dyslipidemia, and carbohydrate metabolism disorders that can develop with diuretic monotherapy. Such combinations are very promising in patients with left ventricular hypertrophy (LVH) and diabetic nephropathy. Potentially a useful combination drug of this composition is Enzix® ( Stada) (enalapril 10 mg + inda-pamide 2.5 mg). Indications for the primary use of Enzix® are shown in Table 5.

Of no less importance is the expected adherence of patients to the treatment of hypertension (Table 6). If it is low, then the use of fixed combinations should also be more actively recommended.

Organoprotective effects of the combined drug Enzix® TO A radioprotective effect

The cardioprotective effect is ensured by the effect of the drug Enzix on LVH - prevention of its development or possible regression of LVH. The multicenter LIVE (Left ventricle hypertrophy: Indapamide Versus Enalapril) study examined the effect of indapamide and enalapril therapy on the regression of left ventricular myocardial mass (LVMM).

Indapamide therapy led to a significant decrease in LVMM (p<0,001). Индапамид также в большей степени снижал выраженность гипертрофии левого желудочка (ГЛЖ), чем эналаприл (p<0,049).

In a study by Bocker W., it was found that indapamide reduces LVMM, suppresses aldosterone activity in plasma and ACE activity in plasma and myocardium.

A number of studies have proven the ability of long-term therapy with enalapril and indapami home to improve the life prognosis of patients with hypertension (TOMSH, STOP–Hypertension 2, ABCD, ANBP2). The randomized, double-blind, placebo-controlled, parallel-group TOMHS trial compared acebutolol, amlodipine, chlorthalidone, doxazosin, enalapril, and placebo. Blood pressure decreased in all groups, but significantly more in the active therapy groups than in the placebo group. Mortality and major cardiovascular events were not significantly higher in the placebo group; no significant differences were found between the active therapy groups.

The randomized, open-label, blinded end-point prospective study STOP-Hyperten-sion 2 compared the use of β-blockers in combination with diuretics (2213 b-x: metoprolol, atenolol or pindolol in combination with hydrochlorothiazide and amiloride), calcium blockers (2196 b–x: felodipine or isradipine) and ACE inhibitors (2205 b–x: enalapril or lisinopril). No significant differences were found in the incidence of fatal cardiovascular events, stroke, heart attack and other vascular mortality.

The randomized, open-label, endpoint-blinded study ANBP2 (6083 patients, duration 4.1 years) comparing the use of enalapril and diuretics found that the risk of cardiovascular events or death in patients receiving ACE inhibitors was 11% lower than those taking diuretics (p=0.05). The ability of enalapril to reduce the risk of complications and death was particularly pronounced in men with respect to the risk of MI.

Many clinical studies on the treatment of hypertension have revealed the ability of enalapril, in addition to lowering blood pressure, to provide a cardioprotective effect (CATCH, PRESERVE). In a 5-year study examining the effect of enalapril on the severity of LVH and QT interval dispersion in hypertensive patients with LVH while achieving and maintaining normal blood pressure levels, a significant decrease in LVMM by 39% was revealed (p<0,001), улучшение сократительной способности миокарда ЛЖ в виде увеличения ФВ (p<0,05) и достоверное уменьшение дисперсии интервала QT, что, помимо снижения риска развития ХСН, может сопровождаться снижением риска развития желудочковых аритмий и улучшением прогноза.

In the randomized, double-blind, placebo-controlled, parallel-group comparison study ABCD (Appropriate Blood Pressure Control in Diabetes), which studied the effect of 5 years of intensive and moderate blood pressure lowering with nisoldipine and enalapril in patients with type 2 diabetes with hypertension (n=470) in comparison with normotensive patients with type 2 diabetes (n=480), a significant reduction in the incidence of MI was shown in the enalapril group (5 versus 25 cases, p=0.001) compared with the nisoldipine group with the same reduction in blood pressure, glucose and blood lipids.

The randomized, double-blind, parallel-group HANE trial compared hydrochlorothiazide (215 patients), atenolol (215 patients), nitrendipine (218 patients), and enalapril (220 patients). Target blood pressure was achieved by week 8: in the atenolol group - in 63.7%, in the enalapril group - in 50%, in the hydrochlorothiazide and nitrendipine groups - in 44.5%. By week 48, effectiveness was 48.0%, 42.7%, 35.4% and 32.9%, respectively. Patients stopped using nitrendipine significantly more often (28 patients, p=0.001).

The randomized, parallel group SLIP trial compared verapamil SR with enalapril. Monotherapy was sufficient in 65.1% of cases. Both drugs significantly reduced blood pressure and levels of total cholesterol, triglycerides and low-density lipoproteins. The effectiveness of enalapril in patients with stage II–IV CHF is confirmed by data from a number of placebo-controlled studies conducted in a double-blind manner (American Heart Association, 1984; Finland, 1986). The results obtained showed that the use of enalapril provides long-term improvement in hemodynamics, expressed in a decrease in the size of the left ventricle (according to echocardiography), a significant increase in ejection fraction (according to radionuclide ventriculography), a decrease in filling pressure and an increase in systolic index. In addition, there was a sustained improvement in symptoms (according to subjective assessmentspatients) and a significant increase in exercise tolerance (assessed byduration of exercise on a bicycle ergometer).

Data obtained during the CONSENSUS research program, which ended in 1987, indicated that enalapril at doses up to 40 mg/day. in combination with therapy with cardiac glycosides and diuretics when taken for 6 months. reduced the risk of death in patients with stage IV CHF by 40%, and when taken for 12 months. – by 31% compared to placebo. After 1 year, all patients were switched to enalapril.

In 1999, an analysis of the fate of all patients participating in this study was carried out. Data collected over 10 years indicate that the risk of death from CHF in the study group was 30% lower than the population average. The study showed that enalapril increases the life expectancy of patients with CHF by an average of 1.5 times. The use of enalapril leads to an increase in the patient's quality of life.

Antianginal effect of enalapril at a dosage of 10 mg/day. (both once and in divided doses) was tested in a number of double-blind, randomized, placebo-controlled studies (Klinische Pharmakologie, Universität Frankfurt am Main, 1988; Institute of Cardiology, University of Cagliari, Italy, 1990) in patients with confirmed ischemic heart disease and normal blood pressure. Efficiency was monitored by the dynamics of changes in the ECG caused by physical activity. Already after the first dose, there was a 22% improvement in the reduction of ST interval; after a 15-day course, the improvement was 35%. In addition, when using enalapril, the threshold for the manifestation of angina pectoris significantly increased and the duration of physical exercise increased. At the same time, the blood pressure level did not change significantly, that is, the observed effect was presumably associated precisely with the improvement of coronary blood flow.

Nephroprotective effect

ACE inhibitors are currently successfully used in nephrological practice. The nephroprotective effect of this group of drugs, associated with the elimination of non-immune mechanisms of progression of renal pathology, remains maximum in comparison with other drugs. The use of ACE inhibitors is indicated both for primary renal diseases (glomerulonephritis of various origins) and for secondary nephropathies (especially diabetic ones). The nephroprotective effect of ACE inhibitors manifests itself at all stages of kidney damage. There are data from a clinical study that included 30 patients with stage I-II hypertension (14 men and 16 women, average age - 55.7 ± 2.1 years), with a duration of hypertension of 12.4 ± 1.8 years without renal dysfunction, which revealed corrective effect of 12-week therapy with enalapril at a dose of 10–20 mg/day. on the glomerular filtration rate (GFR), calculated in the Rehberg test. The patients' blood pressure significantly decreased: from 157.4±2.3/93.6±1.7 to 132.6±6.5/85.5±2.0 mmHg. Art. (p<0,001) с достижением целевого АД у 60% больных. Через 1 мес. терапии в целом достоверно увеличилась СКФ: с 82±3,5 до 110,8±9,0 мл/мин (p<0,05), оставаясь на этом уровне после 3 мес. лечения (111,2±10,2 мл/мин). Исходно сниженная СКФ увеличилась с 72,9±3,6% до 105,5±10,8% (p<0,01); нормальная СКФ не изменилась (97,1±3,6% против 96,3±6,0%). Разнонаправленная динамика СКФ у больных с исходно нормальной и сниженной СКФ свидетельствует об улучшении функционального состояния почек и нефро-протективном эффекте эналаприла.

ACE inhibitors are successfully used in the treatment of renovascular hypertension, but are contraindicated in the presence of bilateral renal artery stenosis or stenosis of the artery of a single kidney due to the risk of a decrease in total glomerular filtration and the development of azotemia.

Of undoubted interest are studies of the effectiveness of enalapril in patients with hypertension and diabetic nephropathy. Ravid M. et al. found that long-term use of enalapril prevents the development of renal dysfunction in patients with type 2 diabetes with microalbuminuria (MAU).

A targeted analysis of the spectrum of ACE inhibitors used by patients with diabetes with preserved renal function and no progression of diabetic nephropathy revealed that in patients receivingenalapril, there was no progression of renal pathology during a follow-up period of 15 years and more.

The nephroprotective effect of antihypertensive drugs is to prevent the development of chronic renal failure. Markers of the nephroprotective effect are microproteinuria - the earliest sign of renal dysfunction, creatinine clearance and albuminuria/creatinine index (AKI>3.4). IAC is 3 times higher in patients with hypertension and 9 times higher in patients with diabetes and, like microproteinuria, is a risk factor for cardiovascular complications. The nephroprotective effect of indapamide was studied in the NESTOR study. In 570 patients with hypertension and type 2 diabetes, the effects of indapamide and enalapril on MAU were compared during 1 year of treatment. There were no differences in antihypertensive effectiveness between the drugs: the degree of reduction in SBP/DBP was 23.8/13 mm Hg. Art. in the indapamide group and 21/12.1 mmHg. Art. – in the enala-pril group. The IAC in patients included in the study was 6.16, and the albumin excretion rate was 58 μm/min, while no disturbances in creatinine clearance were observed. After 1 year of treatment, there was a decrease in IAC to 4.03 (by 35%) in the indapamide group and to 3.74 (by 39%) in the enalapril group, and the rate of albumin excretion decreased by 37% and 45%, respectively. Thus, the nephroprotective effect of indapamide turned out to be comparable to that of enalapril.

Effect on endothelial dysfunction and microcirculation

Data on the ability of enalapril therapy to improve endothelial function (EF) in hypertension were obtained in an open-label, comparative, randomized, crossover study lasting 12 weeks, which included 30 men aged 30–65 years with mild to moderate hypertension. The effectiveness of enalapril (10–20 mg/day) was compared with the non-dihydropyridine calcium antagonist diltiazem (180–360 mg/day). EF was assessed based on endothelium-dependent vasodilation (EDVD) of the brachial artery (cuff test) and biochemical markers - stable NO metabolites in blood serum, expression and activity of the eNOS enzyme in cell culture.

The study found almost identical antihypertensive efficacy of diltiazem and enalapril. An improvement in EF was also revealed during treatment with both drugs. The increase in EDVD during treatment with diltiazem was 4.5±1.2%, and during treatment with enalapril – 6.5±1.0%. In both cases, the increase in EDV compared to the baseline was significant (p<0,005). Улучшение ЭФ на фоне лечения обоими препаратами подтверждалось динамикой биохимических маркеров ЭФ, однако механизм влияния этих препаратов на ЭФ различался: дилтиазем улучшал ЭФ за счет увеличения активности еNOS, тогда как эналаприл – за счет увеличения экспрессии еNOS. Показатель ЭЗВД после лечения эналаприлом был сопоставим с уровнем, который отмечался у обследованных без факторов риска. Таким образом, на фоне лечения эналаприлом происходило выраженное улучшение ЭФ. Возможно, свойство эналаприла улучшать ЭФ (что, по сути, означает дополнительный антиатерогенный эффект) обеспечивало более эффективное уменьшение осложнений в группе пациентов, получавших указанный препарат в исследовании АВСD. При изучении влияния препаратов на метаболические показатели (общего холестерина, триглицеридов, холестерина липопротеидов высокой плотности и глюкозу крови) не было выявлено достоверной динамики, что свидетельствует об их метаболической нейтральности.

There is data from another clinical study that revealed the corrective effect of 12-week therapy with enalapril at a dose of 10–20 mg/day. on microcirculation (MCC) in patients with hypertension. The study included 30 patients with stage I–II hypertension: 14 men and 16 women aged 24–73 years (average age – 55.7±2.1 years) with a headache duration of 12.4±1.8 years. The state of the MCC was studied using laser Doppler flowmetry. The patients' blood pressure significantly decreased: from 157.4±2.3/93.6±1.7 to 132.6±6.5/85.5±2.0 mm Hg. Art. (p<0,001) с достижением целевого АД у 60% больных. Выявлено корригирующее действие эналаприла на все диагностированные патологические типы МКЦ за счет уменьшения спазма и разгрузки венулярного звена микроциркуляторного русла, что сопровождает by improving tissue perfusion.

Thus, enalapril therapy not only has an adequate antihypertensive effect with normalization of blood pressure in 60% of patients with stage I–II hypertension, but also has a corrective effect on the state of the MCC system by reducing spasm and unloading the venular part of the microvasculature. The data obtained indicate an angioprotective effect of therapy based on improved tissue perfusion.

M e tabolic effects

Enzix® does not have an adverse effect on carbohydrate metabolism, blood lipid composition and uric acid concentration, i.e. does not activate risk factors for coronary artery disease, therefore it is indicated for long-term therapy of hypertension in patients with risk factors.

Impact on quality of life

An open, uncontrolled study of the effect of enalapril on the quality of life of patients with hypertension included 244 patients with stage I–II hypertension aged from 25 to 76 years (mean age – 55.0±2.27 years). During the 1 week before the start of the study, patients did not take antihypertensive medications. Then they were prescribed enalapril at a dose of 5–10 mg 1 time/day. within 60 days. Quality of life was assessed according to the main indicators given in the General Well-Being Questionnaire: physical well-being, performance, psychological well-being, sexual abilities. Normalization of blood pressure occurred in 62.9% of patients receiving enalapril at a dose of 10 mg/day, and in 55.3% of patients receiving 5 mg/day. Thus, a good and very good therapeutic effect was achieved in 81.17–90.56% of patients (depending on the dose of the drug). In addition, enalapril therapy led to an improvement in the quality of life in 51.5–59.7% of patients (depending on the dose of the drug).

Side effects of the combination drug Enzix

Enzix® is contraindicated during pregnancy (category C drugs in the first trimester and category D drugs in the second and third) due to its teratogenic effect on the fetus, as well as during breastfeeding (passes into breast milk). For newborns and infants who have been exposed in utero to ACE inhibitors, it is recommended to conduct careful monitoring for timely detection of a pronounced decrease in blood pressure, oliguria, hyperkalemia and neurological disorders, possible due to a decrease in renal and cerebral blood flow. In case of oliguria, it is necessary to maintain blood pressure and renal perfusion by administering appropriate fluids and vasoconstrictor drugs. In general, according to the results of clinical studies, the drug is well tolerated.

However, due to the clinical effects of Enzix®, associated with its effect on ACE metabolism and leading to a decrease in blood pressure, there are a number of pathological conditions in which it should be used with caution due to the risk of developing dangerous side effects. Thus, caution must be exercised when prescribing the drug to patients with a reduced circulating blood volume (limiting salt intake, hemodialysis, diarrhea and vomiting). This is due to the high risk of a sudden and pronounced decrease in blood pressure after using even the initial dose of Enzix®, which, in turn, can lead to loss of consciousness and ischemia of internal organs.

While taking the drug, caution should also be exercised when performing physical exercises and in hot weather due to the risk of dehydration and a concomitant decrease in blood volume.

When taking Enzix® in patients with a history of angioedema (hereditary, idiopathic, or during therapy with ACE inhibitors), there is an increased risk of its development.

The use of Enzix® in a small percentage of cases can cause coughing due to enalapril, which is included in the composition. Typically the cough is non-productive, persistent andstops after the end of treatment.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions (dizziness is possible, especially after taking the initial dose.

Behindinclusion

Enzix® (Stada) is a modern antihypertensive drug that provides not only effective blood pressure control, but also, due to a proven protective effect on all target organs, improves the life prognosis of patients with hypertension.

In modern conditions of limited healthcare financing, when choosing antihypertensive therapy, not only clinical aspects, but also economic ones are taken into account. Studying the cost-effectiveness of the use of antihypertensive drugs allows us to identify their economic advantages. Thus, in a retrospective pharmacoeconomic analysis of several large clinical trials, Enzix® showed better cost-effectiveness ratios in assessing both the degree of blood pressure reduction and the regression of LVH and MAU in comparison with the most commonly prescribed antihypertensive drugs from different classes.

Thus, Enzix® is a representative of modern combination antihypertensive drugs and has a favorable efficacy and safety profile, proven in large clinical studies.

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1 Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after. THEM. Sechenov Ministry of Health of Russia (Sechenov University), Moscow
2 Federal State Autonomous Educational Institution of Higher Education “First Moscow State Medical University named after. THEM. Sechenov" of the Ministry of Health of Russia, Moscow
3 Federal State Budgetary Educational Institution of Further Professional Education RMANPO of the Ministry of Health of Russia, Moscow; Federal State Budgetary Educational Institution of Russian National Research University named after. N.I. Pirogov Ministry of Health of Russia, Moscow

For quotation: Ermolaeva A.S., Dralova O.V., Maksimov M.L. Safe antihypertensive therapy: blood pressure lowering or control? // RMJ. Medical Review. 2014. No. 4. P. 293

Rational antihypertensive therapy remains one of the main problems of cardiology. What is the reason for this interest? On the one hand, this is due to the fact that arterial hypertension (AH) is one of the main risk factors for the development of atherosclerosis, coronary heart disease and leads to cardiovascular complications (CVC), such as myocardial infarction (MI), cerebral stroke (MI) and chronic heart failure. On the other hand, there are a number of pressing but unresolved issues in the treatment of hypertension. Some doctors try to single out one or another group of drugs; they choose irrational combinations of antihypertensive drugs as the drugs of choice for the treatment of hypertension or to quickly reduce blood pressure. However, for some patients, rapid achievement of target blood pressure levels may be accompanied by the development of complications.

Russian guidelines for the diagnosis and treatment of hypertension recommend 5 main classes of antihypertensive drugs: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin I receptor blockers (ARBs), calcium antagonists, β-blockers, diuretics. There is no convincing evidence yet that one class of antihypertensive drugs is superior to others. α-blockers, imidazoline receptor agonists, and direct renin inhibitors may also be used as additional classes. When choosing antihypertensive therapy (AHT), it is necessary first to evaluate the effectiveness, the likelihood of side effects and the benefits of the drug in a specific clinical situation.

A meta-analysis, which included 7 randomized studies (including 4 large clinical studies: Dutch TIA trial; PATS; HOPE; PROGRESS) and a total of 15,527 patients, showed that ADT can reduce the risk of recurrent stroke by 24%, MI - by 21% and cardiovascular events - by 21%.

In the 2013 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) hypertension treatment working group recommendations for the treatment of hypertension, in the seventh report of the US Joint National Commission on the Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC VII) with targeted blood pressure values ​​are defined as a decrease in SBP and DBP less than 140/90 mm Hg. Art. in all patients with hypertension, in patients with diabetes mellitus - DBP<85 мм рт. ст. У лиц старше 80 лет рекомендуется снижать САД до

140-150 mm Hg. Art. and even up to values<140/90 мм рт. ст. при хорошей переносимости .

The fourth revision of Russian recommendations indicates similar target blood pressure values: “Prevention, diagnosis and treatment of arterial hypertension” (RKO/VNOK, 2010): “When treating patients with hypertension, the blood pressure value should be less than 140/90 mm Hg. Art., which is its target level. If the prescribed therapy is well tolerated, it is advisable to reduce blood pressure to lower values. In patients with high and very high risk of cardiovascular events, it is necessary to reduce blood pressure<140/90 мм рт. ст. в течение 4 нед. В дальнейшем, при условии хорошей переносимости рекомендуется снижение АД до 130-139/80-89 мм рт. ст. При плохой переносимости снижения АД рекомендуется его снижение в несколько этапов. На каждом этапе АД снижается на 10-15% от исходного уровня за 2-4 нед. с последующим периодом для адаптации пациента к более низким величинам АД. При достижении целевых уровней АД необходимо учитывать нижнюю границу снижения САД до 110-115 мм рт. ст. и ДАД до 70-75 мм рт. ст., а также следить за тем, чтобы в процессе лечения не увеличилось пульсовое АД у пожилых пациентов, что происходит главным образом за счет снижения ДАД» .

The development of drug-induced hypotension, which increases the risk of renal, myocardial and cerebral hypoperfusion, is one of the most serious problems of AHT. The problem most often discussed in the literature is hypotension of the first dose when prescribing ACE inhibitors. However, the incidence of drug-induced hypotension during treatment with antihypertensive drugs reaches 10%.

In hypertensive patients, hypotension is a common condition that has received insufficient attention in studies of antihypertensive regimens. The most common causes of hypotensive conditions in patients with hypertension are the use of drugs with a pronounced vasodilation effect or causing a decrease in circulating blood volume (CBV), as well as spontaneous hypotension, which develops mainly at night and is caused by impaired autoregulation of vascular tone. The occurrence of drug-induced hypotonic reactions is more typical for dosage forms with rapid release of the active ingredient, which have low T/P (Trough/Peak) values.

The T/P indicator allows us to judge the duration of action of an antihypertensive drug in relation to the residual (i.e., after taking the last dose) to peak (maximum effect at the time of maximum concentration of the drug in the blood) activity. When using drugs with a low T/P index, high blood pressure variability is observed, due to excessive hypotension at the peak of the drug's action or insufficient antihypertensive effect at the end of the dosage interval. A decrease in the total volume of fluid in the body and, as a consequence, BCC can lead to a higher concentration of hydrophilic drugs (atenolol, lisinopril) in the blood. The elimination of antihypertensive drugs from the body may also be slower due to decreased renal filtration and decreased liver enzyme activity, which can often be observed in elderly patients. In addition, due to a decrease in the volume of blood circulation, the use of diuretics is limited.

A significant decrease in blood pressure can occur with combination therapy, when several drugs are used that initially do not provide a rapid antihypertensive effect, the maximum effect of which is delayed and the hypotensive reaction occurs after several hours. It is known that an increase in blood pressure variability in itself is an unfavorable prognostic factor associated with the risk of developing cardiovascular complications in patients with hypertension. At the same time, in elderly people, even while taking long-acting medications, a decrease in DBP during wakefulness may be noted. Often, an excessive decrease in blood pressure is observed when self-administering antihypertensive drugs without blood pressure control due to a deterioration in well-being, which in patients with hypertension is not always associated with an increase in blood pressure.

A number of studies in elderly patients or patients with vascular diseases have found a paradoxical increase in the incidence of cardiovascular events, most likely due to an excessive decrease in blood pressure. According to the Honolulu Heart Study, orthostatic hypotension in the population over 70 years of age is recorded in 7% of cases, and the mortality rate in this category of patients is 64% higher than in the control group.

Neurological complications of antihypertensive therapy, manifested in the form of decreased physical and mental performance, fatigue, tinnitus, dizziness, are observed mainly in elderly patients, especially in the presence of cerebrovascular disease and significant stenoses of the precerebral (carotid and vertebral) and cerebral arteries. In this case, disorders such as sleep disturbances, emotional lability, and depressive states may occur. Sometimes hypoperfusion states can be asymptomatic and can be detected as a decrease in cerebral blood flow based on the results of Doppler ultrasound or magnetic resonance spectroscopy. Apparently, hypoperfusion conditions may be one of the causes of clinically “silent” strokes.

Complications of antihypertensive therapy can be caused by a significant decrease in blood pressure as a result of dysfunction of baroreceptors, when its level falls below the lower limit of autoregulation of cerebral circulation, which leads to cerebral hypoperfusion.

In individuals with normal blood pressure, cerebral blood flow is maintained at a constant level (about 50 ml per 100 g of brain matter per minute), the lower limit of autoregulation of cerebral circulation is about 60 mm Hg. Art., and the upper one is about 180 mm Hg. Art., according to average hemodynamic blood pressure. In patients with hypertension, autoregulation of cerebral blood flow adapts to higher blood pressure values, and the higher the usual blood pressure values, the higher the lower limit of autoregulation of cerebral blood flow. In patients with long-term hypertension, the lower limit of autoregulation of cerebral circulation can reach 90-100 mm Hg. Art. Thus, for a patient with hypertension, a decrease in SBP to a level of 120-130 mm Hg. Art., especially when trying to quickly “normalize” blood pressure, can be critical and lead to a decrease in perfusion blood pressure and the appearance of symptoms of cerebral ischemia.

A study of cerebral blood flow in patients with cerebrovascular pathology shows that cerebral hypoperfusion occurs when blood pressure decreases by an average of 10-20% from normal “working” values.

It has been established that repeated cerebrovascular accident depends not only on the nature of the stroke - cerebral infarction or hemorrhage, but also on the level of maintained blood pressure. After hemorrhage, the risk of recurrent cerebral complications was directly proportional to the level of DBP, with the lowest incidence of cerebral damage observed at DBP≤80 mm Hg. Art. In patients who suffered an ischemic stroke, the lowest risk of recurrent stroke was found in the DBP range of 80-84 mm Hg. Art., and at a lower level, blood pressure increased again. Moreover, after an atherothrombotic stroke, the lowest frequency of recurrence of a cerebral event was observed with a DBP of 85-89 mm Hg. Art., after lacunar (ischemic cerebral infarction) - 80-84 mm Hg. Art., which was associated with limited possibilities of autoregulation of cerebral blood flow with damage to large cerebral arteries.

At the same time, in case of intracerebral hemorrhage, it is recommended to reduce blood pressure gradually and only to normal blood pressure levels for the patient, and if they are not known, then SBP to a level of 150-160 mm Hg. Art., and DBP - up to 85-90 mm Hg. Art. .

The most important factor that undoubtedly influences the determination of the target blood pressure level is the presence of hemodynamically significant occlusive atherosclerotic lesions of the main arteries. Approximately 20% of patients who have suffered a transient ischemic attack or stroke have severe stenosis or occlusion of at least one carotid artery. Carrying out inadequate AHT in such patients can worsen cerebral perfusion with relatively normal blood pressure values ​​and lead to complications, including the development of ischemic hemodynamic stroke. An analysis of the results of several studies that examined the prognostic value of hypertension and AHT in patients with stenosis or occlusion of the carotid arteries showed the following results.

In patients who have suffered an ischemic stroke or transient ischemic attack and have significant stenosis (narrowing of more than 70% of the lumen) of the internal carotid artery, with an increase in blood pressure, the risk of stroke increases to a lesser extent than in patients without severe atherosclerosis. At the same time, in the UK-TIA study in patients with clinically symptomatic unilateral occlusive carotid lesions, an increased risk of stroke was found with a decrease in SBP<130 мм рт. ст. При наличии двустороннего значительного стеноза сонных артерий риск развития инсульта возрастает также при снижении АД. Это обусловлено нарушением нормальной регуляции мозгового кровотока, величина которого определяется перфузионным давлением, напрямую зависящим от системного АД. У больных данной группы, получавших гипотензивную терапию, риск развития инсульта был наименьшим при значениях САД 150-169 мм рт. ст. и прогрессивно многократно увеличивался при более низких значениях. Выраженный двусторонний стеноз сонных артерий является показанием к хирургическому лечению, т. к. только после этого пациентам можно будет проводить активную гипотензивную терапию и снижать АД до уровня, безопасного для сердца, почек и других органов .

Based on the data presented above, for patients with a history of ischemic cerebral events and suffering from discirculatory encephalopathy, 3 main target levels of SBP are recommended as the most prognostically significant with respect to the risk of recurrent cerebrovascular complications:

GARDEN 140-135 mm Hg. Art. optimal for patients with stage 2 hypertension and unilateral carotid stenosis ≥70%;

SBP 120 mm Hg. Art. - the minimum possible for patients with stage 1 hypertension, high normal blood pressure in the absence of severe damage to the main arteries of the head.

There is evidence that with a significant decrease in blood pressure, the risk of coronary complications increases. In the INVEST study, which included 22 thousand patients with hypertension and coronary heart disease, DBP was below 90 mm Hg. Art. was associated with an increased risk of MI compared with the group that had the lowest risk of MI at DBP 82.7 mm Hg. Art. . The SHEP study involving 4736 patients with isolated systolic hypertension showed that when DBP decreased below 70 mm Hg. Art. the risk of developing cardiovascular diseases (CVD), including MI, increases, and the risk of CVD increases by 2 times when DBP is less than 55 mm Hg. Art. .

Patients with severe (occlusive) coronary artery disease and/or left ventricular hypertrophy have a higher risk of coronary complications with low DBP, although this complication is more typical for patients with stage 1 and 2 hypertension in whom the DBP level has decreased by more than by 25 mm Hg. Art. from the original value.

Another negative aspect of a sharp decrease in blood pressure is a decrease in renal perfusion and, as a result, the development of renal failure. Maintaining optimal blood pressure levels is very important for patients with kidney pathology. For adequate renal perfusion, it is necessary to maintain SBP at a level of 80 to 180 mmHg. Art. When SBP decreases below 80 mm Hg. Art. a decrease in renal perfusion and the development of renal failure are possible.

ARBs and ACEIs, by dilating the efferent glomerular arterioles, can cause a decrease in renal perfusion pressure and a decrease in glomerular filtration rate (GFR). The dependence of GFR on the level of angiotensin II becomes especially pronounced with a decrease in blood volume, bilateral renal artery stenosis, as well as renal artery stenosis of a single kidney. Decreased filtration may result in increased serum creatinine and potassium levels. Hypovolemia and hypotension further exacerbate the decrease in filtration.

In recent years, increasing importance has been attached to the indicator of blood pressure variability, since high variability is associated with an increased risk of cardiovascular events.

Patients with the greatest BP variability were 6.22 times more likely to develop a stroke compared to patients with the least variability. It should be noted that in the group of patients with hypertension with increased SBP variability, the frequency of cardiovascular events is 60-70% higher (1372 patients, follow-up time - up to 7.5 years). As a result of a 14-year follow-up of 956 patients, it was revealed that in groups with moderate and high SBP variability, compared with those with low variability, there was an increase in the risk of death by 55 and 49%, respectively.

As you know, blood pressure decreases during sleep and rises quickly before waking up. Maximum values ​​are observed after waking up and starting daily activities. The morning rise in blood pressure causes stress on the cardiovascular system, leading to target organ damage and pathological reactions.

The magnitude and speed of the morning rise in blood pressure depend on the characteristics of the daily blood pressure profile. Moreover, patients suffering from essential hypertension in the early stages of the disease are characterized by a greater magnitude and speed of the morning rise in blood pressure than in healthy individuals. And in patients with an excessive decrease in blood pressure at night, as well as in patients with an insufficient decrease in blood pressure during night sleep, the morning rise is characterized by a greater magnitude and rate of increase in pressure compared to patients with a normal circadian rhythm.

According to a meta-analysis of 4 studies including 3468 patients, high blood pressure variability is an independent predictor of the development of cardiovascular events in patients with hypertension, even without a history of CVD, regardless of age and gender.

Based on a clinical and instrumental examination of 65 patients with acute MI, a significant influence of hypertension with increasing variability on the course of the disease and the annual prognosis of patients was proven. The clinical course of the acute period of MI in patients with high blood pressure variability was more severe. In patients with hypertension, a complicated course with the development of acute left ventricular failure was observed 2 times more often (20.8 and 9.8%, respectively), and recurrent infarctions occurred 3 times more often (8.3 and 2.4%, respectively). It was revealed that during the first year after a heart attack, an increase in blood pressure variability is associated with a 3-fold increase in the risk of death. It has been shown that high blood pressure variability in the acute period of myocardial infarction correlates with deterioration of left ventricular systolic function and is an unfavorable prognostic criterion for the course of myocardial infarction.

During the morning rise in blood pressure, the maximum number of different cardiovascular events occurs. Thus, it has been shown that most ischemic episodes occur in the morning, which coincides with the frequency of MI and sudden death. Most often, MI develops in the first half of the day. In the TIMI II study, the maximum incidence of heart attacks (34%) was observed between 6:00 am and 12:00 pm. The daily rhythm of angina attacks has the same character. The circadian rhythm of variant angina is also characterized by a peak in the morning. It was also found that there is a relationship between the circadian rhythm and ischemic brain damage: nondippers and overdippers have significantly more “silent” cerebral lesions compared to moderate dippers. In a meta-analysis of 31 studies that reported the timing of strokes in 11,816 patients, the odds of having a stroke were 79% higher between 6:00 a.m. and 12:00 p.m. than during other hours. At the same time, in the morning period, the likelihood of all three types of cerebrovascular accidents increased (by 55% for ischemic strokes, by 34% for hemorrhagic strokes and by 50% for transient ischemic attack). It has been shown that the morning rise in blood pressure by 10 mm Hg. Art. is associated with a 22% increased risk of stroke.

Even if office BP is normal, BP is often elevated in the early morning hours. Thus, an analysis of blood pressure using the method of monitoring it at home (the ACAMPA study) was carried out in Spain in 290 treated patients with hypertension, as well as a study of morning hypertension J-MORE (Jichi Morning-Hypertension Research) in 1027 treated patients with hypertension. Both studies demonstrated that in 60% of hypertensive patients in whom treatment appears to be quite effective, blood pressure remains elevated in the morning.

Drug correction of blood pressure variability not only helps prevent MI, stroke, and deaths, but also explains differences in the effectiveness of different antihypertensive drugs in reducing blood pressure. If an antihypertensive drug does not remain fully effective throughout its duration of action, the result may be uncontrolled blood pressure in the morning, even if office blood pressure is normal. A duration of action of the drug of more than 24 hours seems desirable, since many patients are late in taking the next dose, or even completely forget to take it. For a drug to be effective for 24 hours, it is necessary that at least 50% of the peak activity of the active substance is retained by the end of the 24-hour period of action.

Thus, it is necessary to use drugs with a long duration of action to prevent increased BP variability during the day, avoid sharp rises in BP in the morning, and at the same time prevent episodes of sharp decrease in BP. The long-lasting antihypertensive effect and high T/P index allow for more complete organ protection.

Planning the desired level of blood pressure reduction in patients should be based on the compensatory capabilities of cerebral, coronary and renal hemodynamics. The presence of cerebrovascular diseases, coronary heart disease and left ventricular hypertrophy indicates a decrease in the functional reserve of target organs and requires more careful monitoring of the decrease in blood pressure. In the absence of pronounced disturbances in cerebral hemodynamics, it is permissible to reduce SBP by 20% of the initial values, and DBP by 15%. In patients with hypertension, a moderate reduction in blood pressure is advisable - by 10-15% from the initial level over 2-4 weeks. followed by a break to allow the patient to adapt to lower blood pressure values. As the patient adapts to new (lower) blood pressure levels, a further gradual decrease in blood pressure to optimal values ​​for the patient is possible. If moving to the next stage causes the patient's condition to worsen, it is advisable to return to the previous level for some more time. The reduction of blood pressure to the target level occurs in several stages, the number of which is individual and depends on both the initial value of blood pressure and the tolerability of antihypertensive drugs. The use of a step-by-step scheme for lowering blood pressure, taking into account individual tolerance, especially in patients with a high and very high risk of cardiovascular disease, allows one to achieve a target blood pressure level of less than 140/90 mmHg. Art., avoid episodes of hypotension and an increase in the associated risk of developing myocardial infarction and myocardial infarction.

Conclusion

Currently, the effectiveness of rational AHT has been convincingly proven in relation to both the prevention of cardiovascular events and the progression of target organ damage. On the one hand, it is necessary to prescribe drugs with the help of which the target blood pressure level is achieved, on the other hand, it is necessary to monitor so that the decrease in blood pressure does not fall below 110-115/70-75 mm Hg. Art. Gradual and sustained normalization of blood pressure leads to a decrease in the incidence of myocardial infarction, a decrease in the number of recurrent strokes and mortality from CVD.

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Antihypertensive drugs are medications that are aimed at having a hypotensive effect, that is, lowering blood pressure.

Their identical name is antihypertensive (Ukrainian: antihypertensive, drugs that give a hypotensive effect).

The drugs are produced in large quantities, since the problem of high blood pressure is quite common.

According to statistics, antihypertensive therapy has helped reduce mortality in extreme forms of hypertension over the past twenty years by almost fifty percent.

The opposite effect (increasing blood pressure) are hypertensive medications, also called antihypertensives, or those that have a hypertensive effect.

Hypotensive effect, what is it?

The most common diagnosed pathology of the heart and blood vessels is arterial hypertension.

According to statistics, diagnosing signs of this pathological condition occurs in approximately fifty percent of elderly people, requiring timely intervention and effective therapy to prevent complications.

In order to prescribe treatment with drugs that have an antihypertensive effect, it is necessary to accurately diagnose the presence of arterial hypertension in the patient, determine all risk factors for the progression of complications, and contraindications to individual antihypertensive drugs.

Antihypertensive therapy is aimed at reducing blood pressure and preventing all sorts of complications due to kidney failure, stroke, or death of heart muscle tissue.

In a person with high blood pressure, when treated with antihypertensive drugs, the normal blood pressure is not more than one hundred and forty over ninety.

It is important to understand that normal blood pressure readings and the need for antihypertensive therapy are determined for each individual.

However, if complications progress in the heart, retina, kidneys, or other vital organs, treatment should begin without delay.

The presence of a prolonged increase in diastolic pressure (from 90 mm Hg) requires the use of antihypertensive drug therapy, these are the instructions prescribed in the recommendations of the World Health Organization.

In most cases, drugs that have an antihypertensive effect are prescribed for lifelong use, but in some cases they can be prescribed in courses for an indefinite period.

The latter is due to the fact that when the course of therapy is stopped, three quarters of patients experience a return of signs of hypertension.

For a lifelong course of treatment, antihypertensive treatment is selected with the least side effects and complete tolerance of all components by the patient.

Antihypertensive therapy, with long-term use, is as safe as possible, and side effects are caused by incorrect dosage or course of treatment.

For each individual case, the doctor determines his course of treatment, depending on the form and severity of hypertension, contraindications and concomitant diseases.

When prescribing antihypertensive medications, the doctor should familiarize the patient with the possible side effects of antihypertensive drugs.

What are the main principles of therapy?

Since drugs with antihypertensive effects have been prescribed for a long time, and they have been tested by a large number of patients.

Doctors have formed the basic principles for countering high blood pressure, which are given below:

• It is preferable to use drugs that have a long-lasting effect, and helps maintain blood pressure at a normal level throughout the day and prevents deviations in indicators, which can lead to complications;
• Medicines that have an antihypertensive effect should be prescribed exclusively by the attending physician. The prescription of certain antihypertensive drugs should be carried out exclusively by the attending physician, based on the studies conducted and the characteristics of the course of the disease, the already affected organs, as well as the individual tolerance of each of the components of the drug by the patient;
• When using a small dose of antihypertensive drugs, the effectiveness is recorded, but the indicators are still high, then the dosage is gradually increased, under the supervision of the attending physician, until the pressure returns to normal;
• When using combination treatment If the second medication does not have the desired effect, or provokes side effects, then you should try using another antihypertensive drug, but do not change the dosage and course of treatment with the first drug;
• Rapid reduction in blood pressure is not allowed, as this can lead to ischemic attacks on vital organs. This is of particular importance for elderly patients;
• Therapy begins with small dosages of antihypertensive drugs. At this stage, the most suitable remedy with the fewest side effects is selected;
• To achieve the best hypotensive effect, the principles of combined use of antihypertensive drugs are taken into account. Therapy begins with the selection of drugs in minimal doses, with their gradual increase to achieve the desired result. At the moment, in medicine there are schemes for combined treatment of arterial hypertension;
• In modern pharmaceuticals, there are drugs that contain several active ingredients at once.. This is much more convenient, since the patient only needs to take one drug, but two or three different tablets;
• If there is no effectiveness from the use of antihypertensive drugs, or the patient does not tolerate the drug well, then its dosage cannot be increased or combined with other drugs. In this case, you need to completely eliminate the drug and try another one. The range of antihypertensive drugs is very wide, so the selection of effective therapy occurs gradually for each patient.

Classification of antihypertensive drugs

The main antihypertensive medications are divided into two groups. The table below shows the classification in the table by group.

Modern medications are effectively used for arterial hypertension, and can be used as initial treatment or maintenance therapy, either alone or in combination with other drugs.

The choice of one or another drug is made by the attending physician based on the degree of increase in blood pressure, characteristics of the disease and other individual indicators.

What is special about ACE inhibitors?

ACE inhibitors are the best and most effective medications in the antihypertensive group. A decrease in blood pressure when using these antihypertensive drugs occurs under the influence of expansion of the lumen of the vessel.

As the lumen of the vessel increases, the total resistance of the vessel walls decreases, which leads to a decrease in blood pressure.

ACE inhibitors have virtually no effect on the amount of blood ejected by the heart and the number of contractions of the heart muscle, which allows them to be used for concomitant pathology - heart failure.

Effectiveness is felt after taking the first dose of the antihypertensive drug - a decrease in blood pressure is noted. If you use ACE inhibitors for several weeks, the effect of antihypertensive therapy increases and reaches maximum levels, completely normalizing blood pressure.

The main disadvantage of these antihypertensive drugs is the frequent side effects compared to drugs from other groups. They are characterized by: a strong dry cough, a malfunction of taste buds and characteristic signs of increased potassium in the blood.

In very rare cases, reactions of excessive sensitivity, manifested as angioedema, are recorded.

The dosage of ACE inhibitors is reduced in case of kidney failure.

Unconditional contraindications to the use of these antihypertensive drugs are:

• The period of bearing a child;
• High levels of potassium in the blood;
• Sharp narrowing of both arteries of the kidneys;
• Quincke's edema.

A list of the most common antihypertensive drugs, from the group of ACE inhibitors, is given below:

• Gopten– take one to four milligrams, once a day;
• Vitopril, Lopril, Diroton– it is recommended to consume ten to forty milligrams up to two times a day;
• Renitek, Enap, Berlipril– consume from five to forty milligrams, up to two times a day;
• Moex– consume from eight to thirty milligrams, up to two times a day. Recommended for use by people suffering from kidney failure;
• Quadropril– take six milligrams, once a day;
• Phosicard– consume from ten to twenty milligrams, up to two times a day;
• Accupro– take from ten to eighty milligrams, up to two times a day.

What is special about angiotensin II receptor inhibitors?

This group of antihypertensive drugs is the most modern and effective. IRA drugs lower blood pressure by dilating blood vessels, similar to ACE inhibitors.

However, RA inhibitors act more broadly, providing a strong effect in lowering blood pressure by disrupting the binding of angiotensin to receptors in cells of different organs.

It is thanks to this action that they achieve relaxation of the walls of blood vessels and enhance the removal of excess fluid and salts.

Medicines in this group provide effective monitoring of blood pressure for twenty-four hours if RA inhibitors are taken once a day.

Antihypertensive drugs of this subgroup do not have the side effect inherent in ACE inhibitors - a severe dry cough. That is why RA inhibitors effectively replace ACE inhibitors in case of intolerance.

The main contraindications are:

• The period of bearing a child;
• Excess potassium in the blood;
• Narrowing of both arteries of the kidneys;
• Allergic reactions.

The most common drugs of the latest generation

Scroll:

• Valsacor, Diovan, Vazar– take from eighty to three hundred and twenty milligrams per day at one time;
• Aprovel, Irbetan, Converium– it is recommended to consume from one hundred fifty to three hundred milligrams, once a day;
• Mikardis, Prytor– it is recommended to consume from twenty to eighty milligrams, once a day;
• Kasark, Kandesar– used in a dosage of eight to thirty-two grams, once a day.

What are the features of diuretics?

This group of antihypertensive drugs is characterized as diuretics, and is the largest and longest-used group of drugs.

Diuretics have the properties of removing excess fluid and salts from the body, reducing the volume of blood in the circulatory system, the load on the heart and vascular walls, which leads to their relaxation.

The modern group of diuretics is divided into the following types:

• Thiazide (Hypothiazide). This subgroup of diuretics is used most often to lower blood pressure. In most cases, doctors recommend small dosages. The drugs lose their effectiveness in cases of severe kidney failure, which is a contraindication to their use.
  The most common of this group of diuretics is hypothiazide. It is recommended to use in a dosage of thirteen to fifty milligrams, up to two times a day;
• Thiazide-like (Indap, Arifon and Ravel-SR). They use drugs, most often, from one and a half to five milligrams per day (once);
• Potassium-sparing (Spironolactone, Eplerenone, etc.). They have a milder effect compared to other types of diuretics. Its action is to block the effects of aldosterone. They lower blood pressure when removing salts and fluids, but do not lose potassium, calcium and magnesium ions.
  The drugs can be prescribed to people with chronic heart failure and edema caused by cardiac dysfunction.
  Contraindication: kidney failure;
• Loop (Edecrin, Lasix). They are the most aggressive drugs, but they are fast-acting drugs. They are not recommended for prolonged use, as the risk of metabolic disorders increases, because electrolytes are also removed with the liquid. These antihypertensive drugs are effectively used to treat hypertensive crises.

What are the features of beta blockers?

Medicines in this group of antihypertensive drugs effectively lower blood pressure by blocking beta-adrenergic receptors. This leads to a decrease in the blood ejected by the heart, and the activity of renin in the blood plasma decreases.

Such antihypertensive drugs are prescribed for high blood pressure, which is accompanied by angina pectoris and certain types of rhythm disturbances.

Since beta blockers have a hypotensive effect, achieved by reducing the number of contractions, bradycardia (low heart rate) is a contraindication.

When using these antihypertensive drugs, a change in the metabolic processes of fats and carbohydrates occurs, and weight gain can be provoked. That is why beta blockers are not recommended for patients with diabetes mellitus and other metabolic disorders.

These drugs can cause constriction of the bronchi and a decrease in the frequency of heart contractions, which makes them inaccessible to asthmatics and people with irregular contractions.

The most common drugs in this group are:

• Celiprol– consume from two hundred to four hundred milligrams, once a day;
• Betakor, Lokren, Betak– used in a dosage of five to forty milligrams, once a day;
• Biprol, Concor, Coronal– used in a dosage of three to twenty milligrams per day, at a time;
• Egilok, Betalok, Corvitol– it is recommended to consume from fifty to two hundred milligrams per day, you can divide the use up to three doses per day;
• Tenobene, Tenolol, Atenol– it is recommended to consume from twenty-five to one hundred milligrams, up to two times a day.

What is special about calcium antagonists?

With the help of calcium, muscle fibers contract, including the walls of blood vessels. The mechanism of action of these drugs is that they reduce the penetration of calcium ions into vascular smooth muscle cells.

There is a decrease in the sensitivity of blood vessels to vasopressor drugs, which cause vasoconstriction.

In addition to the positive effects, calcium antagonists can cause a number of serious side effects.

This group of antihypertensive drugs is further divided into three subgroups:

• Dihydropyridines (Azomex, Zanidip, Felodip, Corinfar-retard, etc.). Helps effectively dilate blood vessels. They can provoke headaches, redness of the skin in the facial area, accelerate the heart rate, swelling of the extremities;
• Benzothiazepines (Aldizem, Diacordin, etc.). Used in a dosage of one hundred twenty to four hundred eighty milligrams, up to two times a day. May cause severely low heart rate, or blockage of the atrioventricular pathway;
• Phenylalkylamines (Verapamil, Finoptin, Veratard)– it is recommended to consume from one hundred twenty to four hundred eighty milligrams per day. It can cause the same complications as the previous subgroup.

How are hypertensive crises treated?

To treat hypertension crises that occur without complications, it is recommended to lower the pressure not sharply, but gradually, over two days.

To achieve this effect, the following antihypertensive drugs are prescribed in tablet form:

• Captopril– used in a dosage of six to fifty milligrams, for absorption under the tongue. The action begins twenty to sixty minutes after consumption;
• Nifedipine– used internally, or for resorption under the tongue. When taken orally, the effect occurs after twenty minutes, when absorbed under the tongue - after five to ten minutes. May provoke headaches, severe low blood pressure, increased heart rate, redness of the skin in the facial area, as well as chest pain;
• – it is recommended to use in a dosage of 0.8 to 2.4 mg for absorption under the tongue. Effectiveness appears after five to ten minutes;
• Clonidine– taken orally in a dosage of 0.075 to 0.3 mg. The action begins after thirty to sixty minutes. May cause dry mouth and a state of calm and tranquility.

What traditional medicines have a hypotensive effect?

The drugs described above have a persistent hypotensive effect, but require long-term use and constant monitoring of blood pressure.

Beware of the progression of side effects, people, especially the elderly, are inclined to use traditional medicine.

Herbs that have an antihypertensive effect can have truly beneficial effects. Their effectiveness is aimed at dilating blood vessels and sedative properties.

The most common traditional medicines are:

• Motherwort;
• Mint;
• Valerian;
• Hawthorn.

In the pharmacy there are ready-made herbal preparations sold in the form of tea. Such teas contain a mix of various beneficial herbs, mixed in the required quantities, and have a beneficial effect.

The most common herbal infusions are:

• Monastic tea;
• Traviata;
• Tea Evalar Bio.

When registering hypertension, high-quality effective drug therapy is necessary.

Prevention

In order for antihypertensive drugs to have the most effective effect, it is recommended to adhere to preventive measures, which include the following:

• Proper nutrition. The diet should limit the consumption of table salt, any liquids, fast food and other unfavorable foods. It is recommended to saturate your diet with foods that are rich in vitamins and nutrients;
• Get rid of bad habits. It is necessary to completely eradicate the use of alcoholic beverages and drugs;
• Maintain a daily routine. You need to plan your day so that there is a balance between work, healthy rest and good sleep;
• More active lifestyle. It is required to move moderately actively, dedicate at least one hour a day to walking. It is recommended to engage in active sports (swimming, athletics, yoga, etc.);
• Check regularly with your doctor.

All of the above measures will help to effectively reduce the need for consumed antihypertensive drugs and increase their effectiveness.

Video: Antihypertensive drugs, increased bilirubin.

Conclusion

The use of antihypertensive drugs is necessary to counteract hypertension. The range of their choice is quite wide, so choosing the most effective drug for each patient, with the fewest side effects, is a completely doable task.

Prescription of drugs is carried out by the attending physician, who helps to choose a course of treatment in each individual case. The course may consist of one or several drugs, and, in most cases, are prescribed for lifelong use.

The course of antihypertensive drugs can be supported by traditional medicine. It alone cannot be used as the main course of treatment.

Before using any medications, consult your doctor.

Do not self-medicate and be healthy!

At present, there is no doubt about the need for long-term, essentially lifelong, drug therapy arterial hypertension (AG), because even with a decrease blood pressure (HELL) only by 13/6 mm Hg. the risk of occurrence is reduced cerebral stroke(MI) by 40% and myocardial infarction(THEM)– by 16%.

In most cases hypertonic disease (GB) and symptomatic hypertension are asymptomatic, and therefore the elimination of subjective signs of the disease cannot serve as the goal of antihypertensive therapy.

Moreover, when choosing a correction method high blood pressure (HBP) in general, and especially in asymptomatic and minimally symptomatic variants of the course of the disease, it is extremely important, if possible, to give preference to those antihypertensive drugs that do not cause significant deterioration quality of life (QoL) and are available (at a cost) to a specific patient; The frequency of their intake is important (1 or at least 2 times a day).

Goals and treatment strategy for patients with arterial hypertension

The intermediate goal is to prevent the occurrence of structural and functional changes in target organs or cause their reverse change:

– in the heart – reduce the mass of hypertrophied left ventricular myocardium and improve its diastolic function;

– in the kidneys – reduce micro and macroalbuminuria and prevent a progressive decrease in glomerular filtration rate;

– in the brain – reduce the lower and upper limits of autoregulation of cerebral blood flow and slow down the development of stenotic extracranial and intracranial arteries supplying blood to the brain;

– in the retina of the eyes – to prevent the development of grade III-IV hypertensive retinopathy and associated visual impairment.

The ultimate goal is to prevent the development of cerebrovascular accidents, myocardial infarction, sudden death (Sun), heart and kidney failure, and ultimately improve the long-term prognosis, if possible, while avoiding a deterioration in the patient’s quality of life.

The treatment strategy for patients with arterial hypertension is presented in the form of a diagram in Table. 24.

Table 24. Treatment strategy for patients with hypertension, taking into account blood pressure levels, the presence of RF and POM

The table shows that the foundation of antihypertensive therapy is lifestyle modeling, persistent and systematic work to eradicate risk factors(FR). This is the initial, mandatory step in the process of medical supervision of patients with hypertension. In the initial stages of the disease, lifestyle correction is the main way to achieve the required level of blood pressure.

Even with high normal blood pressure, lifestyle changes are advisable due to the high likelihood of developing hypertension in the future. At the same time, in the presence of diabetes mellitus and (or) clinical signs of POM, especially when several risk factors are detected, drug treatment is already implemented for arterial hypertension of the first stage. and even with high normal blood pressure.

Drug therapy for patients with stage II and III hypertension. becomes decisive, but not the only one. U vehicle drivers (VA) and others persons of camera professions(LOP), as in the population as a whole, work on the primary prevention of hypertension in family members (complicated heredity) becomes important. New cases of hypertension should always be an information signal for working with first-generation relatives in the primary prevention program for arterial hypertension.

Considering the effectiveness of non-drug methods - positive dynamics of blood pressure levels and a reduction in the risk of cardiovascular diseases (CVD) in the future, they should always be used in patients with hypertension before starting drug treatment.

So, the basis of the modern strategy for managing patients with hypertension is:

– reduction of blood pressure to the maximum levels tolerated by the patient;

– limiting and (or) minimizing drug treatment;

– elimination or reduction of risk factors (frequency and level) of CVD;

– primary prevention of arterial hypertension and other CVDs in the family.

Currently, the main criterion for starting antihypertensive therapy is not the level of blood pressure, but the patient’s belonging to a certain risk group. If the risk is high, treatment is started immediately, and if the risk is low, antihypertensive therapy is preceded by non-drug treatment lasting 3 to 12 months.

In the presence of diabetes, heart and/or renal failure, drug therapy is indicated for patients with the upper limit of normal blood pressure (130-139/85-90 mm Hg) (in this case, preference should be given angiotensin-converting enzyme inhibitors (ACEI)). Advances in hypertensiology, especially in recent years, are the basis for identifying and determining target blood pressure in the process of supervising patients with hypertension. For each specific patient, the doctor, formulating therapeutic goals, uses all possibilities to achieve an optimal or normal level of blood pressure and reduce overall cardiovascular risk.

Blood pressure correction

Table 25. Target blood pressure levels
To determine the target blood pressure value, it is extremely useful to stratify patients by risk: the higher the risk, the more important it is to achieve an adequate reduction in blood pressure and eliminate other risk factors. At the same time, one should remember that in most cases it is inadmissible to achieve rigid blood pressure levels in a short time using short-acting drugs.

Compliance with this principle is especially important when signs of regional circulatory failure appear and (or) worsen. In this regard, elderly people who have not previously taken drug therapy, as well as patients with cerebrovascular and coronary diseases require increased attention.

An indispensable condition for the successful management of patients with arterial hypertension is the achievement of therapeutic consent, the conscious desire and willingness of the patient to “work” together with the doctor to effectively combat the disease. Trusting, highly professional and humane relationships between them, taking into account the characteristics of the patient’s psychological state and his social status, should be regarded as a significant factor influencing the result of treatment, preventive and health measures.

At the same time, the patient is an active participant in determining the strategy and tactics of treatment, sufficiently informed about the consequences of an untreated disease, possible side effects (PE) therapy, the influence of lifestyle burdened by bad habits and other factors, the nature and characteristics of professional activity on the state of health and the course of hypertension.

Demonstration by a doctor of sincere interest in treatment, the involvement of specialist neurologists, psychologists and psychotherapists, nutritionists in solving individual (medical, psychological and social, personal, professional and other) problems, of course, contributes to achieving the effectiveness of long-term, often lifelong treatment of people with hypertension to prevent progression of the disease and various complications.

In accordance with the recommendations of WHO experts (1999), the choice of drug to start therapy should be made among 6 classes of drugs (diuretics, beta blockers, CCBs, ACE inhibitors, angiotensin II receptor blockers and alpha blockers), and in the presence of uncomplicated hypertension, treatment is recommended to begin with diuretics or beta blockers or a combination thereof.

Beta blockers are considered first-line drugs in the treatment of hypertension. Many years of experience in the use of beta blockers as antihypertensive therapy has proven to be highly effective both in monitoring blood pressure levels and in preventing complications of hypertension.

Modern prospects for the use of beta blockers in patients with hypertension are associated with the search for more advanced drugs that are highly selective for beta1 receptors and also have additional vasodilating properties. Nebivolol is a beta-blocker with high selectivity for beta1 receptors, which has an additional vasodilatory effect associated with modulation of the release of endothelium-relaxing factor (NO) from the vascular endothelium.

Unlike other beta blockers, nebivolol does not increase total peripheral vascular resistance (TPVR), which is especially important in the treatment of hypertension, has a duration of action of more than 10 hours. The effectiveness of nebivolol in monotherapy was shown (67.9%), and in 32.1% of cases a combination with hydrochlorothiazide was required (mainly for stage II arterial hypertension).

Nebivolol after 6 months. treatment has a significant impact on left ventricular hypertrophy (LVH) in patients with hypertension (LVH regression was manifested by a significant decrease in left ventricular myocardial mass by 9.7% and myocardial mass index by 5.1%; in 1/3 of patients with LVH, normalization of myocardial mass was observed). The effectiveness of nebivolol therapy has been established to be 59-70%.

The advantage of beta blockers over diuretics was shown in the multicenter MAPHY study (Metoprolol Atherisclerosis Prevention in Hypertensives, 1991), where mortality from coronary complications and MI among patients with hypertension was significantly lower than when treated with diuretics.

In addition, beta blockers have the ability to gradually reduce blood pressure and prevent its increase and increase in heart rate induced by stress, cause a decrease in the increased activity of renin in the blood plasma, do not lead to orthostatic hypotension, and reduce hypokalemia caused by diuretics.

The beta blocker Betaloc ZOK, the first long-acting form of metoprolol, is highly effective in controlling PAD. Its ability to prevent the main complications of hypertension and reduce mortality from them has been shown: improving the quality of life of patients, safety with long-term use, reducing the risk of developing cardiovascular complications and POM, preventing episodes of peak increases in blood pressure in the early morning hours, which reduces the risk of developing cerebral stroke and myocardial infarction , cardiac arrhythmias, VS and death from progressive heart failure.

The advantages of the new form of metoprolol have been proven in a number of multicenter studies: MERIT-HF, MDC, etc., which demonstrated the high effectiveness of betaloc ZOK in the treatment of heart failure.

The effectiveness of metoprolol SR (betaloc ZOK) at a dose of 50-100 mg in monotherapy has also been registered in 72% of patients with arterial hypertension of stages I and II. The drug was well tolerated: during 4 weeks of treatment, no adverse events requiring discontinuation of the drug were identified. Betaloc ZOK has a beneficial effect on microcirculation, reducing the activation of the sympathetic-adrenal system; in 77.8% of cases after treatment, a normocirculatory type of hemodynamics was recorded.

The highly cardioselective beta-blocker celiprolol (200-400 mg 1 time per day) provides effective blood pressure control in patients with stage I and II hypertension, improves the quality of life and psychological status of patients. The metabolic neutrality of celiprolol in relation to lipid and carbohydrate metabolism has been established.

Based on modern concepts, treatment of arterial hypertension I and II. It is not necessary to start with monotherapy. In some cases, it is possible, and indeed necessary, to prescribe a combination of antihypertensive drugs medicines (medicines).

WHO experts (1999) consider the following combinations rational:

1) diuretic and beta blocker,
2) diuretic and ACEI,
3) diuretic and angiotensin receptor blocker,
4) beta blocker and CCB (dihydropyridine series),
5) beta blocker and alpha1-blocker,
6) ACEI and BCC.

One of the few combinations of a diuretic (6.25 mg hydrochlorothiazide) and a beta blocker (highly selective lipophilic bisoprolol, 2.5-5.0-10.0 mg) - the proprietary name "Ziac" - is considered optimal and effective. The high antihypertensive efficacy of Logimax (a special retard combination of felodipine and metoprolol (form at a dose of 5 mg and 100 mg, respectively) and its good tolerability have been demonstrated in several controlled projects.

According to the International Committee of Medical Statistics (IMS MIDAS 3Q97), the first place in the world when choosing antihypertensive drugs is occupied by CCBs (36%), the second ACEI (34%), the third by beta blockers (13%), followed by diuretics (7%). ) and angiotensin receptor antagonists (2%).

One of the most popular antihypertensive drugs currently are CCBs.

According to modern ideas, an “ideal” BPC must meet the following requirements:

1) selective selectivity to blood vessels and myocardium,
2) high tissue selectivity,
3) slow onset of action,
4) long duration of action,
5) constancy of concentration in the blood,
6) minimum number of PE.

Modern BPCs meet these requirements to varying degrees. The disadvantages of 1st generation drugs (nifedipine, nicardipine) include: rapid onset of action leading to neurohumoral activation; large fluctuations between maximum and minimum concentrations during the interdose interval; short duration of action and the need for repeated administration; high degree of first pass metabolism and variable bioavailability; low tissue selectivity and high incidence of PE.

The disadvantages of second-generation CCBs (nifedipine SR/GITS, felodipine ER, nicardipine SR; new compounds - benidipine, isradipine, nilvadipine, nimodipine, nisoldipine, nitrendipine) are a rapid decrease in activity, causing loss of effectiveness, possible transient activation of the sympathetic nervous system. The so-called 3rd generation BCCs include new compounds that differ in the ionized state of the molecule - amlodipine, or its lipophilicity - lacidipine (lacipil).

In elderly patients with hypertension, due to the presence of multiple concomitant pathologies, age-related characteristics of the pharmacodynamics of antihypertensive drugs and a large number of adverse events, the choice of treatment method is especially difficult. The drug of choice may be amlodipine (Norvasc), which is highly effective in elderly people with arterial hypertension I and II degrees. and providing regression of LVH.

Lacidipine attracts particular attention, the clinical effectiveness of which is presented in a number of studies. Indicated: when taken orally, lacidipine (2 mg/day) causes a distinct hypotensive effect. For sudden asymptomatic increases in blood pressure, a single dose of lacidipine (4 mg) was even more effective and safe than the use of nifedipine at a dose of 20 mg.

Monotherapy with lacidipine (4-6 mg/day) was effective in 91% of patients with stage I and II hypertension; in the remaining 9% of patients, blood pressure was stabilized with a combination of lacidipine and hydrochlorothiazide. According to a double-blind multicenter study, systolic blood pressure (GARDEN) after using lacidipine at a dose of 1 mg it decreased by 12.1 mmHg, at a dose of 2 mg - by 17.7 mmHg, at a dose of 4 mg - by 20.9 mmHg, at a dose 6 mg – 17.7 mmHg, compared to 9.3 mmHg. against a placebo background.

In an open-label, multicenter study, 2206 outpatients received lacidipine for 12 weeks (initial dose 2 mg for those over 65 years of age and 4 mg for younger patients; dose increased by 2 mg if target BP levels were not achieved). After 8 weeks, 29% of patients received lacidipine at a dose of 2 mg, 64.7% - 4 mg and 6.3% - 6 mg, which indicated the effectiveness of this antihypertensive drug in the vast majority of cases (93.7%) at a dose of 2- 4 mg/day.

In another open-label multicenter study, blood pressure levels during lacidipine therapy were assessed in 2127 patients for 1 year. The stable hypotensive effect of the drug persisted throughout the entire observation period (decrease in SBP and diastolic blood pressure (DBP) at 20 and 14 mmHg. respectively), i.e. Tolerance does not develop with long-term use of lacidipine. During therapy with lacidipine, SBP and DBP significantly decreased not only at rest, but also at load height, which was confirmed both during bicycle ergometry and during isometric load.

Currently, the use of long-acting antihypertensive drugs is considered optimal, improving patient adherence to treatment, reducing daily fluctuations in blood pressure and making it possible to more effectively prevent the development of cardiovascular complications and target organ damage.

According to ABPM and the “final/peak” coefficient, the hypotensive effect of lacidipine persists for 24 hours after its administration. A number of comparative studies have shown that the hypotensive activity of lacidipine is at least as good as the effects of nifedipine, amlodipine, atenolol, hydrochlorothiazide, enalapril and captopril.

In a large (1229 patients) multicenter open study CHRIS (Cardiovascular Risk in Hypertension Study), the comparative antihypertensive effectiveness of lacidipine (4-6 mg once daily), atenolol (50-100 mg once daily), and enalapril (10-20 mg once daily) and a combination of hydrochlorothiazide (25-50 mg) and amiloride (2.5-5 mg) once daily.

After one month of therapy, the number of patients who achieved good blood pressure levels was greatest in the lacidipine group (77.5%). Blood pressure decreased in all groups, but SBP and DBP decreased most significantly under the influence of lacidipine and atenolol. It is also important that lacidipine leads to a significant regression of LVH. In addition, the first confirmation of the beneficial effect of lacidipine on the lipid spectrum and the presence of antiatherogenic properties in this drug was obtained.

The incidence of PE during lacidipine therapy was assessed for the period from 1985 to 1995. in 16590 patients. 5297 (31.9%) patients had PE, the frequency of which was higher in women (35.2%) than in men (27.4%). The most common ones are headache, hot flashes, swelling, dizziness and palpitations.

There were no changes in the blood picture or significant biochemical shifts; Lacidipine therapy does not affect glucose levels in patients with type II diabetes mellitus. When treated with lacidipine for 8 weeks, no statistically significant fluctuations in plasma norepinephrine levels were detected compared to the placebo group. A retrospective analysis of the results of treatment with lacidipine in 16,590 patients over 10 years did not reveal any adverse effect of the drug on the incidence of coronary events.

The largest study, ALLHAT (42,448 people), compared the effectiveness of amlodipine (CCB), lisinopril (ACEI) and doxazosin (an alpha-adrenergic receptor blocker) with the effectiveness of the diuretic chlorthalidone in people 55 years and older with hypertension and at least one Risk factors, including previous myocardial infarction and myocardial infarction, revealed a predominance in the number of any cardiovascular events in the doxazosin group (26%) and an overall excess risk of their occurrence compared to the chlorthalidone group (25%).

Chlorthalidone was slightly superior to doxazosin in reducing SBP (DBP levels were the same); those treated with chlorthalidone less frequently required the prescription of additional antihypertensive drugs. Contrary to the common misconception that diuretics are less tolerable, at 4 years more patients were still taking chlorthalidone (86%) than doxazosin or another alpha blocker (75%).

The data obtained indicate the greater effectiveness of chlorthalidone in preventing hypertension, and do not indicate any negative effect of doxazosin. Nevertheless, a document was published in the United States - a clinical warning “Alpha blockers for hypertension”, in which doctors are advised to reconsider their attitude to the use of drugs of this group for the treatment of arterial hypertension.

In 1982, Japanese researchers (Y. Furukawa et al.) showed that imidazole derivatives can act as antagonists of the pressor action of angiotensin II. In the late 80s and early 90s of the last century, drugs were synthesized that have a more selective and more specific effect on the effects of activation of the renin-angiotensin-aldosterone system.

These are AT1-angiotensin receptor blockers, acting as angiotensin II antagonists against AT1 receptors, which mediate the main cardiovascular and renal effects of activation of the renin-angiotensin-aldosterone system. The first imidazole derivative to receive clinical use was losartan (Coaar). This drug and other AT1-angiotensin receptor blockers stand out among modern antihypertensive drugs for their excellent tolerability.

The experience of a clinical study of losartan in almost 3000 patients with hypertension indicates that AEs of its use occur with the same frequency as when prescribing placebo (15.5% versus 15.5%). The most common AEs are headache (4.2%), dizziness (2.4%) and weakness (2.0%), but only dizziness is recorded more often than with placebo (1.3%). The safety of losartan during long-term use in patients with hypertension was demonstrated in the 4-year prospective LIFE study.

In the group of patients taking losartan, mortality was 10% lower than in the group of patients treated with the beta blocker atenolol. There is now direct evidence that losartan improves long-term prognosis in patients with hypertension and chronic heart failure caused by LV systolic dysfunction.

Since 1994, when a representative of the class of AII receptor blockers (losartan) was first registered, irbesartan, valsartan, candesartan and eprosartan (teveten) have been successfully used in clinical practice (along with losartan). Achievement of adequate blood pressure control during treatment with Teveten and favorable metabolic effects in patients with hypertension have been established.

The main goal of treatment of patients with hypertension is to minimize the risk of cardiovascular morbidity and mortality. The currently identified groups of low, medium, high and very high risk of CVD allow individualizing approaches to the treatment of patients with hypertension. Particular attention is paid to the presence of risk factors for CVD, POM and ACS in patients.

Among POM, an important place is occupied by LVH, which leads to a decrease in coronary reserve due to endothelial dysfunction, myocyte hypertrophy and other reasons. There is no doubt that LVH is an independent risk factor associated with increased cardiovascular mortality, primarily due to myocardial infarction, cerebral stroke and VS. LVH is classified as category 1 CV risk factors, the correction of which is shown to reduce cardiovascular mortality.

The principle of treatment of patients with arterial hypertension with and without LVH deserves attention, because assessing the effect of the used antihypertensive therapy on LVH in patients with hypertension is of particular importance, since antihypertensive therapy, leading to regression of LVH, can significantly reduce the risk of developing cardiovascular complications.

If we take into account that LVH is an important prognostic marker of cardiovascular morbidity and mortality, then there is no doubt that in the treatment of hypertensive patients with LVH, preference is given to antihypertensive drugs that, in addition to lowering blood pressure, contribute to the reverse development of LVH, since drugs that reduce blood pressure without affecting myocardial mass of the left ventricle do not appear to reduce the risk of cardiovascular morbidity and mortality.

The most promising in terms of prevention and treatment of patients with hypertension and LVH are considered to be the study of ACE inhibitors, angiotensin II receptor blockers, beta blockers, CCBs and diuretics. The Veterans Study project (452 ​​men who were prescribed one of 6 groups of drugs - a beta blocker, an ACEI, a CCB, an alpha blocker and a centrally acting sympatholytic in a double-blind, randomized manner for 2 years under echocardiography control) established: a) no effect of any short-course drug (8 weeks) on LVH, b) the greatest decrease in left ventricular myocardial mass after 2 years of treatment in the group of captopril (15 g; p = 0.08) and hydrochlorothiazide (14 g; p = 0.05) ; the less pronounced effect of atenolol and clonidine, prazosin and diltiazem did not change the mass of the left ventricular myocardium.

An effective effect of CCBs on LVH, as well as ACE inhibitors, was found. Clinical studies have also found a reduction in myocardial hypertrophy with the use of CCBs associated with arterial hypertension. The ability of nifedipine, verapamil and lacidipine to cause regression of LVH has been demonstrated.

After long-term antihypertensive therapy with captopril, propranolol, hydrochlorothiazide or nifedipine, incl. and combined, the frequency of LVH is reduced, as well as the number of nonspecific changes in the final part of the ventricular complex. At the same time, a meta-analysis of small but well-planned studies of the effect of therapy on the reverse development of LVH showed that ACE inhibitors are the most effective, followed by CCBs, diuretics, and beta-blockers. The TOMHS research project studied mild hypertension and assessed regression of LVH in 902 hypertensive patients.

A pronounced effect of non-drug therapy for hypertension was established and the opinion that there was no effect of diuretics on the mass of the left ventricular mycardium was not confirmed. With regard to the effect on prognostically significant indicators (BP, ECG, EchoCG, left ventricular myocardial mass, blood lipid levels), the drugs from the five studied groups differed slightly.

Long-term therapy with ACE inhibitors leads to a decrease in LVH, normalization of LV diastolic function, a decrease in proteinuria and a slowdown in the progression of renal failure. Numerous studies have shown that diuretics have less effect on the reversal of LVH than ACE inhibitors.

A number of authors note the positive impact of CCB on quality of life (general well-being, physical and social activity, personal life, sleep quality and memory). At the same time, the results of a meta-analysis showed that dihydropyridine CCBs (nifedipine, nitrendipine, nicardipine) have a less pronounced effect on LVH compared to non-hydropyridine CCBs (verapamil, diltiazem).

Some studies have found a decrease in LVH and improvement in LV diastolic function with sufficiently long-term use (more than 6 months) of angiotensin receptor blockers. The LIFE project compared the effects of losartan and atenolol on cardiovascular morbidity and mortality in hypertensive patients with LVH.

The angiotensin receptor blocker telmisartan in a single dose of 40 and 80 mg is an effective antihypertensive agent, uniformly correcting SBP and DBP during the day and night hours, restoring the initially disturbed circadian rhythm of blood pressure, and reducing maximum blood pressure in the morning. Telmisartan is safe with long-term use (24 weeks) and leads to significant regression of LVH.

Elderly patients are also a high-risk group, because they have a significant number of RF, POM and ACS. In addition, the prevalence of isolated systolic hypertension is high in elderly patients. The attitude towards the latter was previously calm, and the severity of arterial hypertension was usually associated with an increase in DBP. However, a number of studies have revealed a connection between systolic hypertension and mortality from CVD, and therefore an increase in SBP is regarded as an independent risk factor that aggravates the prognosis of hypertension.

Selection of antihypertensive drugs

Its antihypertensive activity lasts 24 hours; the high efficacy and safety of indapamide is combined with a safe metabolic profile, a beneficial effect on LVH. At the same time, monotherapy, incl. arifon retard, in elderly patients with isolated systolic arterial hypertension, especially in high and very high risk groups, does not always allow achieving target blood pressure levels.

In most patients, two or more antihypertensive agents are required to achieve the target blood pressure level (less than 140/90 mmHg or 130/80 mmHg in patients with diabetes or chronic kidney disease). If blood pressure is more than 20/10 mmHg above target, consideration should be given to initiating dual-drug therapy, one of which should be a thiazide diuretic.

The most effective therapy prescribed by a qualified physician will achieve blood pressure control only if patients are sufficiently motivated. Motivation increases if patients already have a positive experience with a particular doctor and trust him. Empathy builds trust and is a powerful motivator.

When organizing treatment (primarily medication), it is important to change not only the clinical and hemodynamic parameters of patients, but also the satisfaction of the latter in mental, social and emotional terms. After all, the use of many medications is often accompanied by the development of PE.

In addition, chronic diseases are asymptomatic and mild (for example, hypertension), and the appearance of undesirable signs that limit lifestyle and work activity leads to refusal of therapy. That is why recently the study of the quality of life of patients in general and people of various specialties in particular has been of particular clinical interest.

The study of QoL in hypertension can be a source of additional information about the patient’s condition, his ability to work, and the effectiveness of antihypertensive therapy, which is extremely important in patients with acute pathology or acute illness. Scientific works carried out in the country and abroad have studied the effect of antihypertensive therapy on quality of life. Some studies have found that high blood pressure reduces quality of life, and a correlation has been determined between blood pressure levels and a number of indicators characterizing quality of life.

Considering the need for lifelong medication, in 90-95% of patients with hypertension, the urgent question arises about the need to select drugs that will not only effectively stabilize blood pressure, but also not worsen quality of life, but, if possible, improve it. This problem has received the attention of many foreign and domestic scientists.

In particular, a statistically significant improvement in quality of life was established with the use of ACE inhibitors, CCBs, beta blockers and diuretics; Moreover, the effect of the first two groups of drugs in relation to both stabilization of blood pressure and improvement of quality of life is most pronounced in elderly patients. Enalapril and amplodipine effectively reduce blood pressure to 142/91 mmHg; No deterioration in quality of life was detected; on the contrary, a slight (2-5%) increase in its level was noted.

It is emphasized that the dynamics of QOL significantly depend on its level before treatment. Thus, in patients with initially low QOL, its level after a course of antihypertensive therapy either increased or did not change. At the same time, in subjects with an initially higher quality of life, it did not change when taking captopril, but it worsened when treated with enalapril. Lomir (isradipine) after 12 months of therapy significantly improves a number of quality of life characteristics (memory, patients’ subjective assessment of their personal life and general standard of living, normalization of sleep, tendency to reduce depression).

There was a significant increase in both individual indicators characterizing quality of life and its overall level when treating patients with arterial hypertension with verapamil. A significant increase in quality of life during treatment with the diuretic indapamide is accompanied by a significant decrease in blood pressure and an improvement in biochemical blood parameters. The most controversial literature data are on the effect of beta-blockers on quality of life, which is associated with the variety of drugs in this class and, above all, the large differences between non-selective (propranolol) and selective (bisoprolol, etc.) in terms of the occurrence of PE.

Consequently, therapy with non-selective beta-blockers due to PE (in particular, a negative effect on the sex life of men) may lead to a deterioration in QoL. A number of scientific publications indicate the adverse effects of propranolol on quality of life (including association with depression).

The results of a randomized placebo-controlled crossover study assessing the effect of monotherapy with nifedipine and propranolol on the psychological characteristics and QOL of patients with hypertension confirm the positive effect of the CCB nifedipine on psychological, social status, vital activity and other QOL parameters. At the same time, propranolol after 4 weeks of treatment led to maladaptation, hypochondria and depression.

In summary, it should be noted that ACE inhibitors, CCBs, a number of diuretics (except hydrochlorothiazide) and selective BBs do not worsen the quality of life of patients with hypertension. However, non-selective beta blockers and the diuretic hydrochlorothiazide have a negative effect on the quality of life of patients.

The information provided should become the property of practical healthcare to eliminate the gap between theory and practice in the field of hypertension, and above all, the prevention, diagnosis and treatment of patients with arterial hypertension in accordance with modern scientifically based recommendations.

A.A. Elgarov, A.G. Shogenov, L.V. Elgarova, R.M. Aramisova