Cardiovascular diseases are the most common among the world's population, so a fairly large percentage of people take “heart” medications, and this, as a rule, is not one medicine, but several. In this case, the question arises about their safe combination. In this article we will talk about dangerous combinations of “heart” drugs.

The term “heart medications” is quite general and non-specific. Medicines for the treatment of arterial hypertension, angina pectoris, myocardial infarction, cardiomyopathies, cardiac arrhythmias and conduction disorders, and many others fit this description. To bring some clarity, it is necessary to stipulate that in the article We will talk about the most widely used medications that affect the functioning of the heart, and their possible combinations with each other.

The following groups of drugs will be considered:

Note: all drugs are written by international nonproprietary name (INN).

I. Beta blockers:

1. non-selective: propranolol, carvedilol, oxprenolol, pindolol, nadolol.
2. selective: atenolol, metoprolol, bisoprolol, nebivolol, talinolol.

II. Calcium channel blockers (calcium antagonists):

1. non-dihydropyridine: verapamil, diltiazem;
2. dihydropyridine: nifedipine, amlodipine, S-amlodipine, lercanidipine.

III. ACE inhibitors: captopril, perindopril, enalapril, ramipril, zofenapril, fosinopril, lisinopril.

IV. Angiotensin II receptor blockers: losartan, valsartan, candesartan, ibresartan, telmisartan.

V. Diuretics:

1. thiazide: hydrochlorothiazide, chlorthalidone.
2. thiazide-like: indapamide.
3. loop diuretics: furosemide, torsemide.
4. potassium-sparing diuretics: spironolactone, eplerenone.

Note: the classification shows the most famous representatives of drugs. If you do not find your drug here, then you can find out which group it belongs to by looking at the instructions for it (find the line “pharmacotherapeutic group”), or in reference books on drugs (Vidal, RLS, reference book by M.D. Mashkovsky) .

Recommendations for the treatment of arterial hypertension from 2013, developed by the European Society of Hypertension and the European Society of Cardiology, established the following irrational (i.e. dangerous) combinations"heart" drugs:

1. beta-blockers + non-dihydropyridine calcium channel blockers (verapamil, diltiazem). This combination is a BIG ERROR on the part of the doctor, since drugs of both groups cause a decrease in heart rate. When prescribed together, their total effect on heart rate is so pronounced that life-threatening conditions can occur (even heart rhythm disturbances). If, by coincidence, the patient can only be prescribed a combination of beta-blockers with calcium channel blockers, then from the group of the latter, preference is given to dihydropyridine drugs (nifedipine, amlodipine, lercanidipine).

Note: A combination of beta blockers and non-dihydropyridine calcium antagonists is sometimes used to control ventricular rate in persistent atrial fibrillation. BUT! Only in this case!

2. ACE inhibitor + potassium-sparing diuretic. Potassium-sparing diuretics include spironolactone and eplerenone. Like all diuretics, a group of potassium-sparing drugs removes excess fluid from the body while maintaining potassium in the blood. ACE inhibitors also contribute to the accumulation of potassium in the body. When combining drugs from both groups, a dangerous condition for the heart can occur - hyperkalemia - which can cause cardiac arrest in diastole. If your doctor has prescribed you a drug from any of these groups, you need to periodically check your potassium level (during dose selection, once a week, when the optimal dose of the drug is selected - once a month). The normal level of potassium in blood plasma for adults is 3.5-5.1 mmol/l.

3. Beta-blocker and centrally acting drugs. The latter group includes methyldopa, clonidine, moxonidine, and rilmenidine. These groups have similar mechanisms of action, clinical effects, and - most importantly - side effects. Due to mutual enhancement of undesirable effects, these two groups are not used together.

4. ACE inhibitor and angiotensin-II receptor blocker. Previously, this combination of drugs was possible, but since 2013 it has been established that the combination of these two groups has a negative effect on the kidneys, causing renal failure in a relatively short time.

The same Recommendations talk about possible but less studied drug combinations . It is possible that someday these combinations will move into the group of rational or dangerous. Such combinations include the following:

1. ACE inhibitor + beta blocker;
2. Angiotensin-II receptor blocker + beta-blocker;
3. Dihydropyridine calcium antagonists + beta-blockers.

Rational and as safe as possible The following drug combinations are available:

1. Diuretic (thiazide) + angiotensin-II receptor blocker;
2. Diuretic (thiazide) + calcium antagonist;
3. Diuretic (thiazide) + ACE inhibitor;
4. Angiotensin-II receptor blocker + calcium antagonist;
5. ACE inhibitor + calcium antagonist.

These are, perhaps, all the features of the most common combinations of “heart” drugs. Of course, in each individual case, in relation to a particular drug, there are characteristics unique to it. But the basic rules in prescribing several “heart” medications are the above.

Modern fixed combinations of antihypertensive drugs

G.E. Gendlin, E.I. Emelina

Department of Hospital Therapy No. 2, Faculty of Medicine, Russian State Medical University. N.I. Pirogov

The main goal of therapy for patients with arterial hypertension is to achieve target blood pressure values, for which various combinations of antihypertensive drugs are used. Combination therapy with diuretics and angiotensin-converting enzyme inhibitors has noticeable advantages. A fixed combination of these drugs is Noliprel A, which is a first-line agent in the modern treatment of arterial hypertension.

Arterial hypertension (AH) is one of the most common cardiovascular diseases. According to epidemiological studies, more than a third of the adult population of Russia suffers from hypertension. The main goal of therapy for patients with high blood pressure (BP) is to achieve its target values. According to the recommendations adopted by the European Society of Hypertension together with the European Society of Cardiology, the target blood pressure values are less than 140/90 mm Hg. Art., and in patients with diabetes mellitus (DM) or kidney damage -<130/80 мм рт. ст. Аналогичные значения рекомендуют эксперты Всероссийского общества кардиологов (ВНОК). Достижение оптимального уровня АД является важнейшей задачей при ведении больного АГ.
Increase in diastolic blood pressure for every 5-6 mm Hg. Art. (or systolic blood pressure by 10 mm Hg) increases the risk of developing coronary heart disease by 20-25%, stroke - by 35-40%, chronic heart diseasebirth failure - by 50%. In addition, high blood pressure contributes to the development of left ventricular myocardial hypertrophy, which, in turn, doubles the risk of chronic heart failure and coronary heart disease (regardless of blood pressure level) and 4-9 times increases the risk of severe ventricular arrhythmias.
At the same time, an effective reduction in blood pressure in patients is achieved only in 5-10% of cases. This is due to the fact that in practice it is not always possible to control blood pressure when prescribing only one antihypertensive drug (AGD); there are certain difficulties in selecting adequate doses of AHD to reduce blood pressure to target values; patient adherence to the prescribed treatment also plays an important role.
According to the latest recommendations, one of the first-line drugs can be prescribed as initial therapy for mild and moderate hypertension: a diuretic, an angiotensin-converting enzyme (ACE) inhibitor, a β-blocker, a calcium antagonist, an angiotensin receptor antagonistwell II, and if the blood pressure decreases insufficiently, the dose of antihypertensive drugs can be increased. Meanwhile, essential hypertension is a heterogeneous disease caused by the presence of a large number of factors that contribute to the development of vasoconstriction and the maintenance of elevated blood pressure. The main pathogenetic mechanisms for the development of hypertension are an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), hyperstimulation of the sympathetic nervous system and sodium retention in the body. Monotherapy aimed at correcting only one of the many pathogenetic links of hypertension often does not allow achieving the target blood pressure level. It is not always possible to identify the specific vasoconstrictor mechanism that dominates the pathogenesis of hypertension in each patient, and this partly explains the low effectiveness of treatment with one drug. The results of a number of studies studying the main groups of antihypertensive drugs used as monotherapy have shown that the effectiveness of treating hypertension with one drug is about 50-60%.
In addition, as the dose of antihypertensive drugs increases, the frequency of adverse effects (AEs) increases, and it is not always possible to achieve the target blood pressure level. For example, when using maximum doses of a diuretic as monotherapy, the risk of developing hypokalemia, hyperuricemia and hyperglycemia is quite high, which forces patients to refuse to use these drugs. In addition, during monotherapy with diuretics, counter-regulatory neurohumoral mechanisms are activated, weakening their antihypertensive properties, which requires increasing the dose and contributes to a greater severity of NE. Other NEs are also dose-dependent: cough when using ACE inhibitors, peripheral edema when treated with calcium antagonists. Selection of adequate doses of antihypertensive drugs becomesa problem at the outpatient stage of treatment, when the doctor is deprived of the opportunity to regularly monitor the patient’s condition.
The choice of antihypertensive drugs for the treatment of elderly patients must be approached with special attention. Numerous studies conducted in patients with isolated systolic hypertension have shown that achieving the target blood pressure level significantly reduces the risk of strokes and coronary complications.
An important factor in the treatment of hypertension is the patient’s adherence to the treatment prescribed by the doctor, because even carefully selected therapy may be ineffective if the drugs are not taken regularly. In this regard, factors such as deterioration in quality of life due to the need to take one or more drugs, adverse effects from the therapy, and the cost of drug treatment play an important role. Violation of recommendations significantly weakens the effect of reducing cardiovascular risk in patients with hypertension, mainly due to unsatisfactory blood pressure control. To improve patients' interest in treatment, several strategies have been proposed: informing about the risk of cardiovascular complications of hypertension, selecting drugs with an optimal balance of effectiveness and tolerability, training patients to independently measure blood pressure, etc.
At the start of hypertension therapy, different tactics for prescribing antihypertensive drugs are used. It is possible to use one AGP, and in the absence of a satisfactory effect, titrate its dose or add a second AGP with a different mechanism of action. A common tactic is to replace one drug with another while maintaining the monotherapy regimen. In recent years, fixed combinations of antihypertensive drugs have been increasingly used as first-choice therapy.
Several large randomized controlled trials (SHEP, COOPE, HOT, ALLHAT, INVEST, LIFE, STOP) have demonstrated that 45–93% of patients require antihypertensive therapy with two or more drugs. According to the results of Russian studies that studied the possibilities of treating hypertension in an outpatient setting (ARGUS, QUADRIGA, FAGOT, ROSA, EPIGRAF, etc.), the initial level of systolic blood pressure in most patients ranges from 156 to 178 mm Hg. Art. At the same time, according to multicenter controlled studies, all antihypertensive drugs recommended for use in monotherapy reduce blood pressure approximately equally - on average, only by 11/6 mm Hg. Art. compared to placebo. The need to enhance the antihypertensive effect requires the prescription of combination therapy in most patients with hypertension.
Thus, if previously combinations of antihypertensive drugs were recommended mainly only when monotherapy was ineffective, now combination therapy can be prescribed already at the start of treatment for patients with blood pressure levels more than 160/100 mmHg. Art. when combined with diabetes, proteinuria or chronic renal failure (VNOK Recommendations, 2008).
The main advantages of combination antihypertensive therapy are summarized in the National Guidelines for the Prevention and Treatment of Hypertension (2008). These include the possibility of adequate blood pressure control as a result of the use of drugs with different mechanisms of action and potentiation of their effects. A combination of two or even three antihypertensive drugs in full dose is recommended for the treatment of patients with stage I hypertension with low and moderate risk of cardiovascular complications when full-dose monotherapy is ineffective. Patients with hypertensiongrades 11-111 and in case of high or very high risk, a combination of two drugs in a low dose should be immediately prescribed, and in the absence of a decrease in blood pressure to the target level - 2 drugs in a full dose or 3 in a low dose. If the target blood pressure is not achieved with this treatment, a combination of three antihypertensive agents at full dose is possible. Co-administration of antihypertensive drugs inhibits counter-regulatory mechanisms that begin to act at the start of antihypertensive therapy. Most often, when rational combinations are used, there is no need to prescribe maximum doses, which reduces the risk of NE. Combination therapy more effectively prevents target organ damage and helps reduce the incidence of cardiovascular complications.
There are two combination therapy regimens: the use of two or more antihypertensive drugs in arbitrary dosages and the use of dosage forms with fixed combinations of drugs. The first mode allows for an individual approach to the selection of doses and frequency of administration, while the second provides simple and convenient dosing, increasing patient adherence to treatment.
A special place among combined antihypertensive drugs is occupied by drugs that use lower doses than for monotherapy. Since the effect of most antihypertensive drugs is limited due to the activation of feedback mechanisms, due to the synergistic action of the components of combined antihypertensive drugs, it is possible to achieve significantly greater success in achieving the target blood pressure level. The combination of two drugs with different points of application prevents compensatory responses, which leads to a more significant decrease in blood pressure. In addition, the rationality of the combination and optimal doses of components reduce the risk of NE.
Currently, domestic and international recommendations allowthe use of many fixed combinations for the initial treatment of hypertension, while primarily fixed combinations of small doses are allowed as first-line drugs. The use of low-dose combinations reduces the number of NEs, reduces the cost of therapy and thereby undoubtedly improves patient adherence to treatment. It is estimated that more than 50% of patients with mild to moderate hypertension require combination therapy. If hypertension is accompanied by diabetes or chronic renal failure, the proportion of such patients is significantly larger, since the target blood pressure level is lower.
In recent years, there has been a tendency to increase the frequency of use of combination antihypertensive therapy. According to the recent PYTHAGORUS III study, the majority of doctors (about 70%) prefer to use combination antihypertensive therapy in the form of free (69%), fixed (43%) and low-dose (29%) combinations.
The following requirements are imposed on fixed combinations of antihypertensive drugs: the presence of a complementary effect, improvement of the hypotensive effect when used together, the ability to provide organ protection, the proximity of the pharmacodynamic and pharmacokinetic parameters of the drugs included in their composition. The main rational combinations of antihypertensive drugs are currently considered to be combinations of a diuretic and an ACE inhibitor (or an angiotensin II receptor antagonist), a diuretic and a β-blocker, a diuretic and a calcium antagonist, a calcium antagonist and an ACE inhibitor (or an angiotensin II receptor antagonist), a dihydropyridine calcium antagonist and P-blocker.
Combination therapy with diuretics and ACE inhibitors has noticeable advantages, since with combinedthe use of these drugs often achieves a reduction in blood pressure due to complementary effects. The hypotensive effect of ACE inhibitors is primarily associated with a decrease in the production of angiotensin II, so they are especially effective in patients with increased RAAS activity. The antihypertensive effect of diuretics is limited to some extent by reactive hyperreninemia associated with activation of the RAAS, the severity of which is largely neutralized when ACE inhibitors are prescribed. At the same time, the combination of these groups of drugs is effective not only in patients with increased RAAS activity, but also in patients with normo- and even hyporenin forms of hypertension, which is associated with an increase in the activity of ACE inhibitors in the presence of diuretics. The synergy of these groups of drugs leads to an increase in sodium excretion and a decrease in volume load.
When treated with diuretics, especially in high doses, compensatory activation of the RAAS may occur, leading to a decrease in their hypotensive effect. The addition of an ACE inhibitor to treatment neutralizes this negative neurohumoral effect, increasing the likelihood of the patient's response to treatment by up to 80% compared to diuretic monotherapy. Conversely, diuretics significantly increase the sensitivity of tissues to ACE inhibitors, which allows them to more often achieve a hypotensive effect. In addition, hypokalemia that occurs during treatment with diuretics can be corrected by ACE inhibitors, which can reduce potassium excretion. Also, ACE inhibitors reduce the adverse effects of diuretics on lipid, carbohydrate and purine metabolism. Finally, ACE inhibitors themselves are weak natriuretics, which enhances the effect of diuretics when used in combination. Thus, the combination of a thiazide or thiazide-like diuretic withAn ACE inhibitor allows you to achieve the target blood pressure level while taking lower doses of drugs due to their synergistic effect.
A fixed combination of very low doses of a thiazide-like diuretic (indapamide) and an ACE inhibitor (perindopril) is Noliprel. The pharmacokinetic profiles of perindopril and indapamide in the combination preparation do not change, which makes it possible to take it once a day. Undoubtedly, this improves patient adherence to treatment, reducing the number of medications taken and the frequency of their administration.
The high effectiveness of the fixed combination of perindopril/indapamide has been proven in a number of large experimental and clinical studies. The experiment revealed the specific effect of the perindopril/indapamide combination on the stiffness of large arteries, as well as the nephroprotective properties of the drug: the ability to reduce proteinuria and improve glomerular function.
Among the most important tasks of adequate antihypertensive therapy, it is necessary to note the prevention of strokes. Recent studies have shown that the cerebroprotective effect differs among different groups of antihypertensive drugs. Thiazide and thiazide-like diuretics have demonstrated their effectiveness in primary (MRC and MRCII studies) and secondary (PATS study) stroke prevention. In the prospective placebo-controlled PROGRESS study, the use of combination therapy with perindopril and indapamide significantly reduced the risk of recurrent stroke.
Prevention of vascular complications in patients with type II diabetes mellitus is also a priority task of the healthcare system. ADVANCE is the first and largest study in patients with type II diabetes that usedcombination drugs Noliprel and Noliprel forte. The study included 11,140 patients with type II diabetes (both with hypertension and normal blood pressure) from 20 countries, including Russia. All patients initially received the therapy necessary for diabetes, including antihypertensive drugs.
The results of the ADVANCE study showed that Noliprel and Noliprel forte reduced overall mortality by 14% and cardiovascular mortality by 18% in patients with type II diabetes. In addition, in patients receiving Noliprel or Noliprel forte, the risk of cardiovascular complications is reduced by 14% and the risk of renal complications by 21%. Based on 1 million patients with type II diabetes already receiving drugs for cardiovascular prevention, the planned administration of Noliprel and Noliprel forte for 5 years can additionally prevent 15,000 vascular, 13,300 coronary and 50,000 renal complications and save 13,000 lives.
The results of the ADVANCE study indicate that widespread use of the fixed combination of perindopril and indapamide in patients with type 2 diabetes reduces the risk of death, as well as macro- and microvascular complications, regardless of baseline blood pressure or concomitant therapy typically used in patients with diabetes. The treatments administered in the study were well tolerated and did not require special monitoring or dose titration and are therefore suitable for widespread use in clinical practice.
Having demonstrated its effectiveness, Noliprel has become popular in many countries around the world, however, transportation conditions around the world, with a wide range of temperature and humidity fluctuations, can affect its stability and effectiveness. Therefore, in the context of the globalization of the drug market, there is a need to create a more stable drug with a longer shelf life. WasSeveral stable salts of perindopril were studied and a choice was made in favor of the arginine salt, which has the most acceptable combination of stability and hygroscopicity. So, after 10 years of successful use of Noliprel, new drugs appeared - Noliprel A and Noliprel A forte, which contain the arginine salt of perindopril. For all parameters studied, the arginine salt of perindopril demonstrated an advantage over the previously used tert-butyl-amine salt. In particular, the shelf life of the drug increased from 2 to 3 years, regardless of temperature. The higher stability of the perindopril compound in Noliprel A means that the drug can be used in different climatic zones while maintaining guaranteed effectiveness. This is of great practical importance for Russia, which has 5 climate zones.
The molecular weight of perindopril arginine is almost 25% greater than perindopril tert-butylamine, so to achieve similar plasma concentrations of perindoprilate, a dose of perindopril arginine 5 mg was proposed instead of perindopril tert-butylamine 4 mg (and 10 mg instead of 8 mg). The pharmacokinetic properties of the two perindopril salts were compared in experimental studies, where similar bioavailability was demonstrated. Their bioequivalence was then studied in an open-label, randomized, crossover pharmacokinetic study, where each group received a single oral dose of perindopril in the form of either arginine salt (10 mg) or tert-butylamine (8 mg). The results revealed complete bioequivalence of these doses of perindopril and no differences in other clinical parameters studied.
Thus, pharmacokinetic studies have shown complete bioequivalence of the new perindopril salt in comparison with the previously used one.
It is important to emphasize that the active metabolite, perindoprilat, is formed in the liver from both arginine and tert-butylamine salts. Therefore, all the beneficial effects previously demonstrated in large-scale studies with perindopril tert-butylamine also apply to perindopril arginine. Accordingly, the data from the STRATHE, REASON, OPTIMAX, PICXEL, PREMIER, ADVANCE studies, as well as the Russian STRATEGY study, which studied Noliprel, are fully applicable to Noliprel A.
In countries where the combination drug Noliprel was registered earlier, Noliprel A has the same indication for use - hypertension. Noliprel A and Noliprel A forte are recommended for use in patients with newly diagnosed or previously untreated hypertension. The new packaging of Nolipre-la A - a container with an adsorbent and a dispenser, is more convenient and practical, which can also have a positive impact on patient adherence to treatment. It should be noted that perindo-pril arginine/indapamide (Noliprel A) was included in the List of Vital and Essential Medicines by the Russian Ministry of Health and Social Development in 2009.
The introduction into clinical practice of fixed combinations of very low doses of antihypertensive drugs will ensure effective blood pressure control in a large number of patients with hypertension and at the same time minimize the risk of NE. Noliprel A meets all modern requirements for a first-choice antihypertensive and can be recommended as initial therapy for patients with hypertension of different age groups, including left ventricular myocardial hypertrophy, mild heart failure, and diabetic nephropathy. Today Noliprel A is the first and only low-dose combination drug in Russiawith this drug, providing a rational approach to the treatment of patients with hypertension.

Catad_tema Arterial hypertension - articles

The place of combination antihypertensive therapy in modern treatment of arterial hypertension

Zh. D. Kobalava
Peoples' Friendship University of Russia

CLINICAL PHARMACOLOGY AND THERAPY, 2001, 10 (3)

IT IS WELL KNOWN that normalization of blood pressure in arterial hypertension is achieved very rarely. The best figures achieved in the USA and France are 27 and 33% respectively. In most other regions the figure fluctuates between 5-10%. Back in 1989, data from the Glasgow Blood Pressure Clinic study confirmed the dominant role of treatment-induced blood pressure levels in the prognosis of arterial hypertension (AH) and clearly demonstrated high rates of cardiovascular mortality and morbidity with insufficient blood pressure reduction. These provisions were later confirmed in the HOT study. A combined regimen of antihypertensive drugs as a tool for normalizing high blood pressure has always been present in the pharmacotherapeutic arsenal of hypertension. However, views on the place of combination therapy in the treatment of hypertension have been repeatedly revised. The first fixed combinations of antihypertensive drugs (reserpine + hydralazine + hydrochlorothiazide; alpha-methyldopa + hydrochlorothiazide; hydrochlorothiazide + potassium-sparing diuretics) appeared in the early 60s. In the 70s and 80s, the leading place was taken by combinations of a diuretic, usually in a high dose, with beta-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 the Monotherapy mode. Monotherapy with high doses of 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 higher antihypertensive activity of angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists 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. A new round in the evolution of this approach is associated with the advent of fixed low-dose combinations of antihypertensive drugs in the late 90s. These were combinations that did not contain a diuretic (calcium antagonist + ACE inhibitor; dihydropyridine calcium antagonist + beta-blocker) or contained it in low doses. Already in 1997, the list of antihypertensive drugs in the report of the US Joint National Committee (VI) included 29 fixed combinations. The feasibility of low-dose combination rational antihypertensive therapy, especially in patients at high risk of developing cardiovascular complications, was confirmed in the latest WHO/International Society of Arterial Hypertension (1999) and DAG-1 (2000) recommendations.

Thus, in the history of combination antihypertensive therapy, the following stages can be distinguished: I - the use of combinations containing rauwolfia derivatives and/or components in high doses; II - the use of combinations of diuretics in high or medium doses with beta-blockers, potassium-sparing diuretics, ACE inhibitors and III - the predominant use of fixed combinations without diuretics (beta-blocker + dihydropyridine calcium antagonist; calcium antagonist + ACE inhibitor) or containing diuretics in low doses (hydrochlorothiazide 6.25-12.5 mg; indapamide 0.625 mg)

Significant variability in the antihypertensive effect of different drugs has been repeatedly confirmed in cross-sectional and longitudinal clinical studies. However, the search for reliable criteria for individual drug selection has been unsuccessful. At the same time, the effectiveness of monotherapy with antihypertensive drugs of different classes is generally comparable: 40-50% of patients respond to treatment. A return to combination therapy is often associated with the results of the HOT mega-study, which confirmed the necessity of achieving a target blood pressure level to truly reduce cardiovascular risk. To solve this problem, combination therapy was required in 2/3 patients. Similar data were obtained from a retrospective analysis of most cited studies on hypertension (Fig. 1). The lower the required target pressure level (for example, in patients with diabetes mellitus and renal failure), the more drugs the patient requires. Thus, the relevance of combination antihypertensive therapy can be justified by the following provisions: the influence of drugs of various classes on different physiological systems involved in the regulation of blood pressure, and a proven increase in the number of patients responding to treatment, up to 70-80%; neutralization of counterregulatory mechanisms aimed at increasing blood pressure; reducing the number of required visits; the possibility of faster normalization of blood pressure without increasing the frequency of adverse events (often it decreases); frequent need for rapid and well-tolerated reduction in blood pressure and/or achievement of low target blood pressure values in high-risk groups; possibility of expanding indications for prescription.

Rational combination therapy must meet a number of mandatory conditions: safety and effectiveness of the components; the contribution of each of them to the expected result; different but complementary mechanisms of action; higher efficiency compared to that of 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; reducing the number of adverse events and improving tolerability. In table Table 1 shows the undesirable consequences of using the main classes of drugs and the possibility of eliminating them by adding a second drug.

TABLE 1. Adverse effects of antihypertensive drugs and possibilities for their elimination

Preparation A	Possible effects of drug A	Corrective drug
Dihydropyridine AAs	Activation of the SNS, heartbeat	Beta blocker
Dihydropyridine AAs	Peripheral edema	ACE inhibitors
Diuretic	Hypokalemia, hypomagnesemia, insulin resistance (?), activation of the RAS and/or SNS	ACE inhibitors, AT 1 receptor blockers
Antiadrenergic drugs	Fluid retention, edema, pseudoresistance	Diuretic
Diuretic	Dyslipidemia	Alpha blocker
Beta blocker	Sodium retention, decreased cardiac output and renal blood flow	Diuretic
Beta blocker	Peripheral vasospasm	Calcium antagonist
Alpha blocker	Vasodilation, first dose hypotension, postural hypotension	Beta blocker
Note: AA - calcium antagonist, RAS - renin-angiotensin system, SNS - sympathetic nervous system

The use of a combination of two drugs that have similar pharmacodynamic properties can lead to different consequences in terms of quantitative interaction parameters: 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 2).

TABLE 2. Possible combinations of antihypertensive drugs

Established rational combinations

Possible rational combinations

Possible, but less rational combinations

Irrational combinations

Combinations whose rationality requires clarification

Combination therapy does not always mean an increase in the antihypertensive effect and can lead to an increase in adverse events (Table 3).

TABLE 3. Adverse effects of combined use of antihypertensive drugs

Preparation A	Drug B	Adverse effects enhanced by drug B
Diuretic	Vasodilators	Hypokalemia
Non-dihydropyridine AAs	Beta blocker	Atrioventricular block, bradycardia
Alpha blocker	Diuretic	First dose hypotension, postural hypotension
ACE inhibitor	Diuretic	Decreased glomerular filtration rate
ACE inhibitor	Potassium-sparing diuretic	Hyperkalemia
Diuretic	Beta blocker	Hyperglycemia, dyslipidemia
Hydralazine	Dihydropyridine AAs	Palpitations, myocardial ischemia
Dihydropyridine AK	Alpha blocker	Hypotension
ACE inhibitor	Alpha blocker	Hypotension

There are different ways to use combination therapy. Two, three or more drugs can be prescribed sequentially, gradually titrating the doses of the components. After achieving the target blood pressure, the selected combination can be used for long-term maintenance therapy. Fixed combination drugs, for the creation of which improved dosage forms are used, are very valuable for rational treatment. 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; 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, and lack of confidence in the need for all components used. Additional requirements for combination drugs are the absence of unpredictable pharmacokinetic interactions and an optimal ratio of residual and maximum effects. A rational selection of components creates the prerequisites for prescribing drugs once a day, which with Monotherapy have to be used two or even three times a day (some beta-blockers, ACE inhibitors and calcium antagonists).

Thiazide diuretic + potassium-sparing diuretic: amiloride + hydrochlorothiazide, spironolactone + hydrochlorothiazide, triamterene + hydrochlorothiazide (Triampur). This combination helps prevent the loss of potassium and magnesium, but is currently practically not used, given the availability of ACE inhibitors, which not only effectively prevent hypokalemia and hypomagnesemia, but are also better tolerated.

Thiazide diuretic + beta blocker: Tenoretic (atenolol 50 or 100 mg + chlorthalidone 25 mg), Lopressor (metoprolol 50 or 100 mg + hydrochlorothiazide 25 or 50 mg) and Inderid (propranolol 40 or 80 mg + hydrochlorothiazide 25 mg). A combination of the two most well-studied classes of antihypertensive drugs. A beta blocker modulates the following possible consequences of diuretic use: tachycardia, hypokalemia and activation of the renin-angiotensin system. A diuretic can eliminate sodium retention caused by a beta blocker. There is evidence that such a combination provides blood pressure control in 75% of cases. However, it is necessary to clarify the consequences of long-term use of this combination due to the possible adverse effects of the components on lipid, carbohydrate, purine metabolism, as well as sexual activity.

Diuretic + ACE inhibitor or AT receptor blocker. Highly effective combinations that provide an effect on two main pathophysiological mechanisms of hypertension: sodium and water retention and activation of the renin-angiotensin system. 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%. Blockers of the renin-angiotensin system eliminate hypokalemia, hypomagnesemia, dyslipidemia, and carbohydrate metabolism disorders that can develop with diuretic monotherapy. The use of the AT 1 receptor blocker losartan helps reduce uric acid levels. Such combinations are very promising in patients with left ventricular hypertrophy and diabetic nephropathies. The most well-known combination drugs of this composition are Caposide (captopril 25 or 50 mg + hydrochlorothiazide 15 or 25 mg), Co-Renitek (enalapril 10 mg + hydrochlorothiazide 12.5 mg), Gizaar (losartan 50 mg + hydrochlorothiazide 12.5 mg). Noliprel, which is a combination of perindopril 2 mg with the metabolically neutral diuretic indapamide 0.625 mg, has additional beneficial potential.

ACE inhibitor + calcium antagonist. ACE inhibitors neutralize the possible activation of the sympathoadrenal system under the influence of calcium antagonists. Based on their ability to activate this system, calcium antagonists are arranged in the following order (in descending order): short-acting dihydropyridines, long-acting dihydropyridines, non-dihydropyridine calcium antagonists. Having venodilating properties, ACE inhibitors reduce the incidence of peripheral edema that develops as a result of arteriolar dilatation under the influence of calcium antagonists. On the other hand, the natriuretic effect of calcium antagonists creates a negative sodium balance and enhances the hypotensive effect of ACE inhibitors. There is encouraging experience with the clinical use of such combinations. In particular, in the FACET study, the best rates of cardiovascular morbidity and mortality were achieved in the group of patients receiving fosinopril and amlodipine. In the HOT study, the calcium antagonist felodipine was supplemented in the second step with an ACE inhibitor in a low dose. It was this largest study that examined the effect of combination antihypertensive therapy on the risk of adverse outcomes, demonstrating the ability to achieve target diastolic blood pressure in more than 90% of patients. Over the past year, the results of the HOPE study have been widely discussed, which are of great interest from the point of view of the effectiveness of combination therapy for hypertension in high-risk groups. Blood pressure was elevated in 47% of patients included in this study; most of them also suffered from coronary artery disease. The frequency of combined use of ramipril with calcium antagonists was 47%, with beta-blockers - 40%, diuretics - 25%. The combination of a calcium antagonist and an ACE inhibitor is attractive from the point of view of enhancing not only the cardioprotective, but also the nephroprotective effect. Currently, there are several fixed combinations of drugs of these classes: Lotrel (amlodipine 2.5 or 5 mg + benazepril 10 or 20 mg), Tarka (verapamil ER + trandolapril in the following doses in mg - 180/2, 240/1, 240/ 2, 240/4), Lexel (felodipine 5 mg + enalapril 5 mg).

Calcium antagonist (dihydropyridine) + beta-blocker. This combination is rational from the standpoint of hemodynamic and metabolic interaction. Numerous data indicate not only the theoretical validity, but also the practical value of the combination of the highly vasoselective dihydropyridine calcium antagonist felodipine and the cardioselective 3-blocker metoprolol in doses of 5 and 50 mg (Logimax). The components have been well studied in multicenter clinical studies. In the HAPPPY, MAPHY studies , MERIT HF demonstrated the following effects of metoprolol and metoprolol SR: a significant reduction in overall and cardiovascular mortality, including in heart failure; a pronounced cardioprotective effect in the treatment and prevention of myocardial infarction; no effect on carbohydrate and lipid metabolism. The calcium antagonist felodipine is evidence-based The database occupies one of the leading positions not only in its class of drugs, but also among all antihypertensive drugs.In clinical studies of NOT, V-HeFT, STOP-HYPERTENSTON-2, the following effects of felodipine were established: reduction of total peripheral vascular resistance and load on the myocardium; increased cardiac output at rest and during exercise; increasing tolerance to physical activity; significant reduction in left ventricular hypertrophy; improvement of rheological properties of blood; 24-hour blood pressure control with once daily use; high efficiency and good tolerability at all stages of hypertension, regardless of age; effectiveness in frequently concomitant hypertension conditions, such as coronary heart disease, diabetes mellitus, obliterating endarteritis; no contraindications (except for hypersensitivity) and, most importantly, a clear beneficial effect on cardiovascular morbidity and mortality, including in high-risk groups (elderly people with diabetes). The possibility of using metoprolol and felodipine in relatively low doses allows the Logimax components to fully demonstrate their cardioselective and vasoselective properties. Logimax is a unique dosage form that provides controlled release of active drugs over 24 hours. Felodipine is a gel matrix containing metoprolol microcapsules. After contact with the liquid medium, a gel shell is formed, with the gradual destruction of which felodipine and microcapsules with metoprolol are released.

The place of combination therapy in modern treatment of arterial hypertension

The initial choice of drug treatment tactics for hypertension often plays a critical role in the future fate of the patient. A successful choice is the key to high adherence to treatment; an unsuccessful choice means lack of blood pressure control and/or failure to comply with doctor’s orders. The choice of the initial regimen for drug correction of hypertension remains empirical. In accordance with the traditional algorithm, it is considered advisable to start treatment with one drug in a minimum dose. Subsequently, the dose is increased or a second drug is added. However, such an approach can hardly be considered always justified. Modern drugs intended for basic treatment of hypertension show their full potential after 4-6 weeks, so the selection of antihypertensive therapy can last for many months, requiring repeat visits and often additional examinations. Certain indications for the primary use of drugs (Table 5) do not allow shortening this period due to variable individual tolerability.

TABLE 5. Established indications for the predominant use of certain antihypertensive drugs

Previously, long-term monotherapy was strongly recommended for patients with so-called “mild” hypertension. Taking into account the modern clinical interpretation of hypertension in terms of risk level, such a recommendation can be extended only to a small group of patients with a low level of cardiovascular risk. In patients with high and very high risk, fixed combinations should be used more often already at the first stage of treatment. 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.

TABLE 6. Factors influencing adherence to treatment

Thus, at present we can use two fundamental approaches to the drug treatment of hypertension: sequential monotherapy until the selection of an effective and well-tolerated drug, or combination therapy in the mode of sequential prescribing of drugs or the use of fixed combinations of antihypertensive drugs. Both approaches have advantages and disadvantages. Modern ideas about the pathogenesis of hypertension attract attention to fixed low-dose combinations, which can increase the effectiveness of treatment, reduce the risk of adverse events and increase patient adherence to treatment and, therefore, optimize therapy in a large number of patients. However, further large-scale controlled studies are needed to examine the impact of these relatively new drugs on informative intermediate outcomes and long-term prognosis.

Literature

I Zadionchenko V.S., Khrulenko S.B. Antihypertensive therapy in patients with arterial hypertension with metabolic risk factors. Wedge. Pharmacol. ter., 2001, 10 (3), 28-32.
2. Kobalava Zh.D., Kotovskaya Yu.V. Arterial hypertension 2000. (edited by V.S. Moiseev). Moscow, "Forte Art", 2001, 208 p.
3. Prevention, diagnosis and treatment of primary arterial hypertension in the Russian Federation (DAG 1). Wedge. Pharmacol. ter., 2000, 9 (3), 5-31.
4. Dahlof V., Hosie J. for the Swedish/United Kingdom Study Group. Antihypertensive efficacy and tolerability of a fixed combination ofmetoprolol and felodipine in comparison with the individual substances in monotherapy. J. Cardiovasc. Pharmacol., 1990, 16, 910-916.
5. Hansson L, Himmelman A. Calcium antagonists in antihypertensive combination therapy. J. Cardiovascular. Pharmacol., 1991, 18 (10), S76-S80.
6. Hansson L., Zanchetti A., Carruthers S. et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet, 1998, 351, 1755-1762.
7. Opie L., Mcsserii F. Combination drug therapy for hypertension. Authors Publishing House. 1997.
8. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch. Intern. Med., 1997, 157, 2413-2446.
9. Sica D., Ripley E. Low-dose fixed-combination antihypertensive therapy in hypertension. A companion to the Brenner and Rectors" The Kidney. W.B.Saunders, 2000, 497-504.
10. World Health Organization-International Society of Hypertension. 1999 World Health Organization-International Society of Hypertension guidelines for the management of hypertension. Guidelines subcommittee. J. Hypertens., 1999, 17, 151-183.

Kolosov A.S. 1, Proshin A.V. 2

1.2 4th year student of the Faculty of Medicine, Kirov State Medical Academy of the Ministry of Health of Russia

COMPARISON OF THE COST OF COMBINATIONS AND COMBINATION DRUGS WITH FIXED DOSES OF ANTIHYPERTENSIVE MEDICINES

annotation

This article compares the costs between different antihypertensive drug combinations and fixed-dose combinations of multiple antihypertensive drugs. The information may be useful to medical professionals for selecting more affordable and accessible pharmacological therapy for the patient in the treatment of arterial hypertension.

Keywords: antihypertensives, combinations, comparison, cost.

Kolosov A.S. 1, Proshin A.V. 2

1,2 Student of the Internal Medicine Faculty, Kirov State Medical Academy

COMPARISON OF COSTBETWEEN COMBINATIONS AND COMBINED FIXED-DOSE ANTIHYPERTENSIVE DRUGS

Abstract

This article compares the cost between the various combinations of antihypertensive drugs and combined fixed-dose multiple antihypertensive drugs. The information may be useful for the health workers to select budget available for the patient pharmacological therapy in the treatment of hypertension.

Keywords: antihypertensive, combinations, compare, cost.

Introduction

The term “arterial hypertension” means the syndrome of increased systolic blood pressure (SBP) ≥ 140 mmHg. Art. and/or diastolic blood pressure (DBP) ≥ 90 mm Hg. Art.

Arterial hypertension (HTN) remains one of the most pressing health problems worldwide.

Arterial hypertension is a leading risk factor for the development of cardiovascular (myocardial infarction, stroke, ischemic heart disease, chronic heart failure), cerebrovascular (ischemic or hemorrhagic stroke, transient ischemic attack) and renal diseases (chronic kidney disease).

The need to lower blood pressure in hypertension has a convincing evidence base and is recognized by almost all doctors.

Combined therapy– a promising approach to the treatment of hypertension
The initial stage of drug treatment of hypertension involves the use of one antihypertensive drug in low or medium therapeutic doses, which is often ineffective. Increasing the dose of the drug is often accompanied by side effects. As a result, some patients either stop treatment altogether or do not achieve adequate blood pressure control.

The undeniable advantages of combination therapy are:

Significant enhancement of the antihypertensive effect. The prescription of rational combinations determines not just a mechanical addition of the effectiveness of two drugs, but a potentiation of their action.
Reduced incidence of side effects. This is due to the fact that in combination therapy, lower doses of the drugs included in the combination are used, and the lower the doses, the fewer side effects.
Increasing the number of patients who respond to treatment, i.e. in whom the administration of the drug will lead to the desired reduction in blood pressure.
The most effective protection of the target organs of hypertension and, therefore, a more effective reduction in the risk of complications.

Thus, rational combination antihypertensive therapy makes it possible to achieve a good antihypertensive effect in the maximum number of patients, which is combined with excellent tolerability, safety of treatment and pronounced organoprotective properties.

The purpose of the work is to determine the cost of different combinations of antihypertensive drugs and compare them with the cost of fixed-dose combination drugs of several antihypertensive drugs.

Research objectives:

Determine the cost of different combinations of antihypertensive drugs and determine the most expensive and cheapest combination.
Determine the cost of fixed-dose combination drugs of several antihypertensive drugs and determine the most expensive and cheapest drug.
Comparison between the cost of a combination of antihypertensive drugs and a fixed-dose combination of the same drugs.

The following were chosen for comparison:

combinations of antihypertensive drugs:

ACE inhibitor (enalapril 20 mg - 28 pcs.) + thiazide diuretic (hydrochlorothiazide 25 mg - 20 pcs.);
ARB (losartan 100 mg – 30 pcs.) + thiazide diuretic (hydrochlorothiazide 25 mg – 20 pcs.);
ACEI (lisinopril 10 mg - 30 pcs.) + AK (amlodipine 5 mg - 30 pcs.);
ARB (losartan 50 mg – 30 pcs.) + AK (amlodipine 5 mg – 30 pcs.);
BAB (metoprolol tartrate 50 mg – 30 pcs.) + AK (felodipine 5 mg – 30 pcs.);
AK (amlodipine 10 mg – 30 pcs.) + BAR (valsartan 160 mg – 28 pcs.);
thiazide diuretic (hydrochlorothiazide 25 mg - 20 pcs.) + potassium-sparing diuretic (veroshpiron 25 mg - 20 pcs.);

combination drugs with fixed doses of antihypertensive drugs:

Ko-renitek (enalapril 20 mg, hydrochlorothiazide 12.5 mg) – 28 pcs.
Gizaar (losartan 100 mg, hydrochlorothiazide 12.5 mg) – 28 pcs.
Equator (amlodipine 5 mg., lisinopril 10 mg.) -30 pcs.
Amzaar (amlodipine 5 mg, losartan 50 mg) – 30 pcs.
Logimax (felodipine 5 mg, metoprolol tartrate 50 mg) – 30 pcs.
Exforge (amlodipine 10 mg, valsartan 160 mg) - 28 pcs.
Triampur (triamterene 25 mg, hydrochlorothiazide 12.5 mg) – 50 pcs.

ACEI - angiotensin-converting enzyme inhibitor, ARB - angiotensin II receptor blocker, AA - calcium antagonist, beta blocker - beta-blocker.

Research results:

The study determined the cost in rubles of various combinations of antihypertensive drugs and fixed-dose combination drugs, and the difference between their costs. The results are presented in Table 1.

Table 1.

Thus, it was found that the cheapest combination of antihypertensive drugs is the combination ACEI + AK(Lisinopril + Amlodipine) and is 127 rubles, and the most expensive is AK + BAR(Amlodipine + Valsartan) and is 388 rubles. The most expensive combination drug with a fixed dose was Exforge and its cost was 1828 rubles, and the cheapest was Korenitek with a cost of 325 rubles.

It was also determined that any of the combinations of antihypertensive drugs does not exceed the cost of fixed-dose combination drugs of the same drugs included in the combinations. The largest percentage difference was the difference between the combination ACEI + AK(Lisinopril + Amlodipine) and the drug "Equator" and is 80% (498 rubles), and the smallest difference is between the combination (Hydrochlorothiazide + Veroshpiron) and the drug "Triampur" and is 33% (108 rubles).

Conclusions:

The most expensive combination of antihypertensive drugs was AK + BAR(Amlodipine + Valsartan), and the cheapest - ACEI + AK(Lisinopril + Amlodipine).
The most expensive fixed-dose combination drug was Exforge, and the cheapest was Korenitek.
Any combination of antihypertensive drugs does not exceed the cost of a combination drug. The biggest difference was between the combination ACEI + AK(Lisinopril + Amlodipine) and the drug "Equator", and the smallest difference is between the combination thiazide diuretic + potassium-sparing diuretic(Hydrochlorothiazide + Veroshpiron) and the drug "Triampur" .

Literature

Encyclopedia of medicines and pharmaceutical products. [Electronic resource] URL: http://www.rlsnet.ru/ (date accessed December 16, 2015)
State register of medicines. [Electronic resource] URL: http://grls.rosminzdrav.ru/ (access date 12/17/2015)
Diagnosis and treatment of arterial hypertension. Clinical recommendations. [Electronic resource] URL: http://cardioweb.ru/klinicheskie-rekomendatsii/ (date accessed 12/17/2015)
Combination therapy for arterial hypertension: focus on non-fixed combinations. [Electronic resource] URL: http://medi.ru/doc/g243803.htm (access date 12/18/2015)
Russian medical journal. Combination therapy for arterial hypertension: what's new? [Electronic resource.] URL: http://www.rmj.ru/articles/kardiologiya/Kombinirovannaya_terapiya_arterialynoy_gipertonii_chto_novogo/ (accessed December 17, 2015)

References

Jenciklopedija lekarstv i tovarov aptechnogo assortimenta. URL: http://www.rlsnet.ru/ (Accessed 12/16/2015)
Gosudarstvennyj reestr lekarstvennyh sredstv. URL: http://grls.rosminzdrav.ru/ (Accessed 12/17/2015)
Diagnostika i lechenie arterial'noj gipertenzii. Klinicheskie rekomendacii. URL: http://cardioweb.ru/klinicheskie-rekomendatsii/ (Accessed 12/17/2015)
Kombinirovannaja terapija arterial’noj gipertonii: fokus na nefiksirovannye kombinacii. URL:http://medi.ru/doc/g243803.htm (Accessed 12/18/2015)
Russian medicinskij zhurnal. Kombinirovannaja terapija arterial’noj hypertonii: what’s new? URL: http://www.rmj.ru/articles/kardiologiya/Kombinirovannaya_terapiya_arterialynoy_gipertonii_chto_novogo/ (Accessed 12/17/2015)

Cardiologist

Higher education:

Cardiologist

Saratov State Medical University named after. IN AND. Razumovsky (SSMU, media)

Level of education - Specialist

Additional education:

"Emergency Cardiology"

1990 - Ryazan Medical Institute named after Academician I.P. Pavlova

Hypertension, being a constantly elevated blood pressure above normal, requires immediate correction of the patient's condition. After all, its complications can pose a serious threat and danger to human health and even life. And combination antihypertensive drugs, which have gained significant popularity today due to their high efficiency and the elimination of the need for patients to take a large number of medications at a time, have firmly taken one of the leading positions in the list of effective drugs designed to stabilize blood pressure.

Rational combinations of antihypertensive drugs provide the opportunity to both increase the effectiveness of the therapeutic intervention and eliminate possible negative manifestations for the patient’s body. Modern formulas of such drugs make it possible to stabilize blood pressure in a short time and reduce the negative impact of hypertension. The psychological factor that determines the patient’s lack of dependence on a large number of medications taken is also important, because combination therapy for arterial hypertension is recognized today as one of the most effective methods of truly effective treatment for high blood pressure.

The most effective combinations of two drugs with antihypertensive effects

The following list of drugs, represented by a combination of two antihypertensive drugs, is considered the most popular among cardiologists due to the positive results of numerous studies aimed at studying the dependence of blood pressure indicators on the drugs used.

And although some of them have not become widely known due to the relatively small scale of laboratory studies, the results of using these drugs speak for themselves: a persistent decrease in blood pressure and stabilization of the patient’s condition are the best indicators of health for this disease.

Combination of thiazide diuretics and β-blockers

This combination has become most widely known due to its excellent performance in the treatment of such conditions as uncomplicated hypertension. It is these components that have proven to be an effective combination even in the presence of concomitant organic lesions in an unadvanced stage of development.

However, gout, physical activity of the patient (for example, athletes), as well as the state of atrioventricular block of 2 and 3 degrees should be considered a contraindication to the use of this combination. Relative contraindications to the use of a combination of thiazide diuretics and β-blockers include pregnancy.

Combination of thiazide diuretics and ACE inhibitors

When using a combination such as thiazide diuretics and ACE inhibitors in the treatment of hypertension, the presence of the following diseases must be taken into account:

congestive heart failure;
hypertension;
isolated systolic hypertension;
elderly people with advanced hypertension.

The listed conditions and diseases are best cured with a combination of thiazide diuretics and ACE inhibitors.

Both components of the presented combination have a high degree of effectiveness, which should be taken into account when prescribing the combined drug to a patient: an excessively rapid decrease in blood pressure can negatively affect the patient’s general well-being. Elderly people are most susceptible to this influence, therefore in this age category the drug in question should be used as a potent substance and therapeutic effects should be carried out with extreme caution.

Combination of “diuretics and AT1 receptor blockers”

This combination has proven itself best in the treatment of high blood pressure in the presence of concurrent lesions of the left ventricle of the heart. However, due to the increased effectiveness of the effect (a sharp decrease in blood pressure), increased caution should be exercised.

The combination of diuretics with AT1 receptor blockers has proven to be excellent in the treatment of severe hypertension in the presence of parallel ongoing progressive chronic heart failure.

Combination of “diuretics and imidazoline I1 receptor agonists”

This combination is not widely known due to the paucity of laboratory studies of the effect on blood pressure in hypertension. However, effectiveness has been observed in many cases of practical use of this combination, and it is excellently used when it is necessary to use complex antihypertensive drugs in the event of allergic reactions or the body’s immunity to treatment with β-blockers.

Combination of diuretics and calcium antagonists

The combination under consideration makes it possible to obtain positive dynamics of treatment in the presence of a pronounced increase in blood pressure in old age, since calcium antagonists belonging to the dihydropyridine series manifest themselves as potent vasodilators in such therapy. Moreover, according to numerous laboratory studies, this combination can eliminate the consequences of high blood pressure, heart failure in the chronic stage and significantly reduce the negative manifestations of ISH.

Combination of β-blockers and ACE inhibitors

Having pronounced effectiveness in hypertension, chronic heart failure and ISH, the combination of ACE inhibitors and β-blockers makes it possible to eliminate the manifestations of high blood pressure in the shortest possible time. Also, this complex of substances allows you to eliminate or minimize the residual effects of coronary heart disease, myocardial infarction in combination with chronic heart failure.

Although this combination is less effective than the combination of diuretics and beta-blockers, studies have provided information about the possibility of treatment using the presented components.

Combination of dihydropyridine calcium antagonists and β-blockers

This combination makes it possible to almost completely cure hypertension in patients with concurrent coronary heart disease. Through research, evidence has been obtained of the effectiveness of medicinal effects using these components.

With the help of these combined drugs, it becomes possible to increase patients' adherence to treatment, which guarantees the most lasting effect and ensures long-term results.

Combination of calcium antagonists and ACE inhibitors

The combination of these components provides an excellent opportunity for the most effective treatment of high blood pressure when combined with pronounced signs and manifestations of nephropathy, pronounced manifestations and documented atherosclerosis.

With the help of calcium antagonists, a positive effect can be obtained in the treatment of hypertension against the background of coronary heart disease, since these substances have a pronounced anti-ischemic effect. ACE inhibitors have proven themselves to be renoprotective components, so they will be correctly prescribed if patients have signs of diabetic nephropathy.

Combination of dihydropyridine calcium antagonists and AT1 receptor blockers

This combination has proven to be most effective in eliminating high blood pressure against the background of existing gout, heart rhythm disturbances and after coronary artery disease. These properties of the combination in question were identified during laboratory studies, which confirmed the high effectiveness of the treatment of people with the listed organic disorders.

Also, this combination showed positive results in eliminating the signs of diabetic nephropathy in diabetes mellitus.

Combination of “ACE inhibitors and imidosaline receptor agonists”

This combination is not currently widely used due to its insufficiently studied effect. However, its use has made it possible to obtain excellent results in eliminating the manifestations of diseases and pathological conditions such as increased excitability of the sympathetic nervous system and coronary heart disease.

A decrease in blood pressure, stabilization of the patient’s general condition with a gradual elimination of the consequences of increased activity of the SNS - these positive effects make it possible to call the combination of ACE inhibitors with imidosaline receptor agonists one of the most promising and effective combinations.

The listed two-component combinations make it possible to increase the degree of impact of the treatment process for arterial hypertension. High blood pressure, accompanying pathological conditions in the form of a significant deterioration in the patient’s health, the presence of concurrent ongoing diseases (ischemic heart disease, chronic heart failure) - these conditions can be corrected and significantly improved through the use of the two-component combinations listed above.

An additional alternative to complex drugs with antihypertensive effects

Today, in the practice of treating high blood pressure, three-component drugs can be used, which have shown excellent results in eliminating the cause of this condition and the consequences of its occurrence. However, they can be considered more theoretical research, since there have not been enough practical experiments to study their degree of effectiveness.

These include the following list of funds:

diuretics, β-blockers and calcium antagonists, which should be called one of the most potent combinations;
diuretics, calcium antagonists and ACE inhibitors - this combination can be used to eliminate the effects of high blood pressure, which ensures reliable improvement of the patient’s condition;
A1 receptor antagonists, calcium antagonists and diuretics.

The listed combinations of drugs are highly effective when used in the treatment of severe hypertension, in the presence of many organic disorders accompanying this pathological condition. Fixed combinations of antihypertensive combinations have already been sufficiently studied, which makes it possible to use them both to treat the underlying lesion with increased blood pressure, and to prevent possible negative manifestations.

The main direction of use of the listed combinations of drugs increases the patient’s desire to use them, which significantly contributes to the effectiveness of the therapeutic effect.

Possibilities for using the most common combinations for high blood pressure

If we present all the most commonly used complex drugs with antihypertensive effects and their combinations in the fight against hypertension, we can obtain the following table, which presents the possibilities for the use of such drugs:

Combinations of drugs and substances	Potential Applications
β-blockers + diuretics	High blood pressure (hypertension), uncomplicated hypertension that does not cause end-organ damage
Diuretics + ACE inhibitors	Persistent arterial hypertension with elevated blood pressure + congestive heart failure, current in chronic form (CHF)
Diuretics + AT1 receptor blockers	Presence of hypertension, isolated systolic hypertension (or ISH) + chronic heart failure. Possibly during ISH.
Diuretics + imidazoline I1 receptor agonists	If it is impossible to include a β-blocker in combination with a diuretic (due to existing contraindications)
Diuretics + calcium antagonists (dihydropyridine series)	Chronic heart failure against the background of sharply increased blood pressure, ISH (most often in elderly patients)
α-blockers + β-blockers	Hypertension, its malignant variety
β-blockers + ACE inhibitors	Patients with arterial hypertension who have had a myocardial infarction (secondary prevention), with CHF and/or coronary artery disease
Calcium antagonists + β-blockers	Arterial hypertension + ischemic heart disease
Calcium antagonists + ACE inhibitors	Arterial hypertension + signs of nephropathy, ischemic heart disease or developing atherosclerosis
Calcium antagonists + AT1 receptor blockers	Arterial hypertension + manifestations of nephropathy, ischemic heart disease or the initial stage of atherosclerosis
ACE inhibitors + AT1 receptor blockers	Arterial hypertension + atherosclerosis + nephropathy
ACE inhibitors + imidazoline I1 receptor agonists	Patients with SNS hyperactivity
Diuretics + β-blockers + calcium antagonists	Malignant arterial hypertension
Diuretics + calcium antagonists + ACE inhibitors	Malignant ISH, long-term arterial hypertension + nephropathy and diabetes mellitus
Diuretics + calcium antagonists + AT1 receptor blockers	Malignant ISH, hypertension + diabetes mellitus with signs of nephropathy
ACE inhibitors + α1-blockers + imidazoline I1 receptor agonists	Arterial hypertension + diabetes mellitus. Metabolic syndrome may develop
ACE inhibitors + calcium antagonists + β-blockers	Long-term arterial hypertension + coronary artery disease

This table clearly shows the possibilities for using certain combinations of the listed components. The effectiveness of using any of the listed drugs depends on the presence of certain indications, and their action is based on certain metabolic and hemodynamic properties of each component.

Recommendations for treatment with antihypertensive complex drugs

An important point in obtaining pronounced positive dynamics with the help of the drugs considered should be considered the need for both preliminary diagnostics to make an accurate diagnosis, and contacting a specialist in his field, who will help draw up the most effective treatment regimen, taking into account the individual characteristics of the body and the presence of concomitant organic changes. To treat arterial hypertension, you should fully follow the advice of your doctor and not self-medicate.

Self-medication in this case can only harm the healing process through the use of the listed medications, therefore, to obtain the expected result, it is recommended to consult a doctor and follow all his recommendations. Making certain adjustments to the treatment being carried out will prevent a decrease in the degree of effectiveness of the impact.

Dangerous combinations of cardiac medications. The most effective (rational) combinations of antihypertensive drugs Rational combinations of antihypertensive drugs octagon