The results of the HOPE and EUROPA study suggest a new clinical direction in the use of ACE inhibitors to slow the progression of atherosclerosis-related diseases. However, if we strictly rely on the principles of evidence-based medicine, we can talk about the protective effect of perindopril in treating patients with stable ischemic heart disease (CHD) and the universal protective effect of ramipril in treating all patients with clinical manifestations of atherosclerosis (CHD, strokes, peripheral atherosclerosis). Can the protective effect of ramipril and perindopril, associated with slowing the progression of atherosclerosis, be transferred to the entire class of ACE inhibitors? The answer must be negative, because in relation to other drugs in this regard there is no evidence base. Moreover,in the placebo-controlled PEACE study involving 8290 patients with stable angina without signs of heart failure, the addition of 4 mg of trandolapril during basic therapy did not lead to an additional reduction of complications . Similarly, in the placebo-controlled study CAMELOT, which involved 1991 patients with stable coronary artery disease without signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complicationswhich involved 1991 patients with stable coronary artery disease with no signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complications compared with the patientwhich involved 1991 patients with stable coronary artery disease with no signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complications compared with the patient placebo therapy . It is not by chance that only ramipril and perindopril are recommended in the European guidelines for the diagnosis and treatment of stable angina for these patients in terms of slowing the progression of the disease and improving the prognosis of this category of patients from an ACE inhibitor . Similarly, in the second revision of the Russian recommendations on chronic heart failure for the prevention of this disease in patients with coronary artery disease, the prescription of either ramipril or perindopril is recommended as having an evidence base . Moreover, ramipril has an evidence base in relation to the anti-atherogenic effect. The SECURE study, which was carried out within the framework of HOPE, studied the effect of ramipril and vitamin E on the condition of the carotid arteries, examined using the ultrasound method. Was shown,that long-term ramipril therapy delayed the progression of carotid atherosclerosis in patients with atherosclerosis or diabetes mellitus who did not have heart failure . Largely due to this research, in the latest European guidelines for the treatment of AH 2007, a new niche for the use of ACE inhibitors has appeared – a concomitant terosclerosis of the carotid arteries . In another program MICRO-HOPE in the framework of the study NORE in 3577 patients with type 2 diabetes mellitus ramipril reduced the risk of microvascular complications of diabetes mellitus, such as chronic renal failure by 24% (p = 0.027) and retinopathy by 22% (p = 0.024) . In a double-blind, randomized trial of AASK, a pronounced nephroprotective effect of ramipril was demonstrated. In the case of 1094 patients with hypertensive nephropathy (glomerular filtration rate (GFR) within 20–65 ml / min), ramipril at a dose of 2.5–10 mg is more effective than amlodipine and metoprolol slowed the decrease in GFR, the development of chronic renal failure and prolonged the life of patients . Thus, the above studies indicate a powerful vazoprotective effect of ramipril, which has important clinical significance. In clinical practice, in addition to the traditional use of ramipril in hypertension and heart failure,It is necessary to provide patients with practically any manifestations of atherosclerosis – coronary, cerebral and great vessels, as well as patients with nephropathy. At present, an effective generic generic of ramipril – charter has appeared on the Russian pharmaceutical market. A preliminary analysis of a recently completed proprietary study indicates a high antihypertensive efficacy and safety of the charter. Summing up, the overview of international and Russian data presented above makes it possible to take a fresh look at the possibilities of an ACE inhibitor. Traditional niches for the use of ACE inhibitors (hypertension, cardiac insufficiency, diabetic nephropathy) have expanded in recent years thanks to the powerful vasoprotective effect of ACE inhibitors, which opens up new clinical possibilities for their use – in terms of slowing the progression of diseasesassociated with atherosclerosis. At the same time, it is necessary to understand that this effect is not inherent in the whole class of drugs, but is characteristic only of ramipril (charter) and perindopril. At least, based on evidence from evidence-based medicine, a protective effect on the progress of cardiovascular diseases can only be talked about these two drugs.
In recent years, ARA has made a huge leap forward in terms of conquering new niches for the treatment of hypertension in various clinical situations. If earlier this class of drugs was in the shadow of an ACE inhibitor (their prescription for hypertension was limited mainly by situations related to side effects due to the administration of ACE inhibitors), then at present the niche of their use, as follows from Table 1, extensive. To better understand the possibilities of ARA, it is necessary to recall their mechanism of action. It is known to inhibit the angiotensin II receptor AT1 – conductors of the main negative effects of this hormone – as a result of which, unlike the ACE inhibitor, the synthesis of AII is not disturbed. The negative effects of AII include vasoconstriction, increased secretion of endothelin, stimulation of the synthesis of peroxide radicals, hypertrophy of smooth muscle cells,increased activity of tissue activator inhibitor type 1 plasminogen. Many of these effects are atherogenic. On the other hand, angiotensin II stimulation of unblocked type 2 receptors (AT2) causes effects opposite to those listed above, namely, vasodilatation, increased production of nitric oxide, and stimulation of antiproliferative processes. Thus, ARA have a double positive mechanism of action, which has a powerful anti-thrombogenic potential.
An illustration of the possibilities of ARA is the LIFE study (a study of the effectiveness of losartan in reducing end points in people with arterial hypertension), the results of which were expected with great interest and are likely to be discussed for a long time [8, 59]. In this study, not only was antihypertensive efficacy of ARA proved for the first time in terms of its effect on end points, but other possibilities were also demonstrated.
In a double-blind, randomized, controlled international study, 9193 hypertensive patients aged 55–80 years participated, with left ventricular hypertrophy. The study participants were randomized into 2 groups for the purpose of treatment as initial with either losartan or atenolol. The initial dose of drugs was, respectively, 50 mg of lazan 1 time per day and 50 mg of atenolol 1 time per day. The drugs could be combined with hydrochlorothiazide – 12.5 mg per day and further increase their dose to 100 mg per day in order to achieve the target blood pressure reduction of less than 140/90 mm Hg. Art. Finally, if the maximum doses of the studied drugs in combination with a diuretic did not provide adequate control of blood pressure, then it was allowed to prescribe additional drugs (with the exception of ARA, ACE inhibitors and BB). The duration of the study averaged 4.8 years.
The objective of the study was to study the comparative efficacy of losartan and atenolol in order to reduce the main endpoint, which included a total of MI, MI and cardiovascular mortality. Other endpoints included the incidence of diabetes mellitus, all-cause mortality, regression of left ventricular hypertrophy, the frequency of hospitalizations for angina or heart failure.
In total, 508 cases of a combined endpoint were detected in the losartan group , and 588 in the atenolol group. Thus, compared to atenolol, losartan reduced the frequency of the main endpoint (cardiovascular mortality, MI and MI) by 13% (p <0.021). The frequency of fatal and nonfatal MI in the losartan group was 25% lower than in the atenolol group (p <0.001), despite the fact that the blood pressure in both groups decreased almost the same – by 30/17 mm Hg. in the group of losartan and at 29/17 mm Hg in the group atenolol. However, there were no differences in the incidence of myocardial infarction in both groups. Another important finding is the significantly lower incidence of diabetes in the Losar group – by 25% (p <0.001). In the subgroup of patients with initial diabetes, the frequency of the main endpoint was lower by 24% (p <0.031), and the rate of cardiovascular mortality was 37% (p <0.028) in the losartan group than in the atenolol group. This indicates a beneficial side effect of losartan. Thanks to this study, a new niche for ARA – AG and myocardial hypertrophy has appeared, since it was shown that a significantly more regressive hypertrophied left ventricle was observed in the subgroup of individuals with losartan compared with atenolol. It was also important thatthat the frequency of side effects when using losartan was significantly less than in the atenolol group. As a result, at the end of the study, significantly more patients continued to take losartan than atenolol.
New possibilities in the treatment of such a problematic group of patients as hypertension with concomitant CHF are associated with ARA. As is known, currently in the treatment of hypertension with CHF, an arsenal of drugs is successfully used that can effectively eliminate the symptoms of heart failure and prolong the life of such patients. These classes of drugs, as is known, include ACE inhibitors, BB, diuretics, and cardiac glycosides. For a long time, the ACE inhibitors, considered to be the gold standard for treating CHF, lacked an alternative to blocking the renin-angiotensin system, which is absolutely necessary in CHF. However, there are a number of situations where patients do not tolerate an ACE inhibitor. In addition, for unknown reasons, the effectiveness of ACE inhibitors in women is significantly lower than in men. In these situations, the doctor needs an alternative to an ACE inhibitor.And this alternative appeared due to the data obtained in the CHARM project, which combined three studies. In a placebo-controlled study CHARM-ALTERNATIVE with more than 2000 patients with CHF, the effectiveness of candesartan in the treatment of patients not taking ACE inhibitors due to their intolerance was studied . The results showed that in case of an intolerance to an ACE inhibitor, the use of candesartan reduces the incidence of MTR and mortality from them, and also reduces the frequency of hospitalization due to the progression of CHF (Fig. 7).in the case of an intolerance to an ACE inhibitor, the use of candesartan reduces the incidence of mortality and mortality from them, and also reduces the frequency of hospitalization due to the progression of heart failure (Fig. 7).in the case of an intolerance to an ACE inhibitor, the use of candesartan reduces the incidence of mortality and mortality from them, and also reduces the frequency of hospitalization due to the progression of heart failure (Fig. 7).
In another study, CHARM-ADDED , it was found that the addition of candesartan to IAP F and BB in patients with CHF leads to a clinically significant decrease in the incidence of CCO and death from them, as well as hospitalization due to progression CHF .
In both of these studies , the use of candesartan was characterized by good tolerability. It is not unimportant to note that the effectiveness of desa-sartan was almost the same in both men and women. A comparative analysis of the results of the CHARM project and the SOLVD study showed that the effectiveness of candesartan in order to reduce the risk of death from SSO and the frequency of hospitalization due to the progression of CHF is comparable to the effectiveness of the standard ACE enalapril. It is very important for practical physicians to know the dose titration rules. candesartan, which was used in the CHARM project. The starting dose is 4 mg per day once, which with stable blood pressure and the absence of complications, it doubled every 3-5 days until reaching 16 mg per day. The maximum dosage per day is 32 mg. To date, the use of candesartan in the treatment of patients with CHF is the most reasonable, and it can be used on a par with an ACE inhibitor (evidence grade A). This fact is reflected in the latest European and Russian recommendations on the diagnosis and treatment of CHF. Moreover, in the latest European guidelines for the treatment of hypertension, a new niche for the use of ARA has appeared – a concomitant CHF. Of the other representatives of the ARA, it is also recommended to use losartan and valsartan. In the new recommendations for the diagnosis and treatment of hypertension, there is also a very interesting niche for the use of ARA – preventing the development of atrial fibrillation in patients with a history of arrhythmia paroxysms.All of these new APA niches indicate the most important pleiotropic effect of this class – organ protection, not associated with a decrease in blood pressure.
As clinical practice shows, in most cases it is possible to achieve target blood pressure against the background of combination therapy with drugs with different mechanisms of action, especially in groups of patients with high risk, which are observed among practitioners. This is quite natural, since a single class of drugs is not able to control all the pathogenetic mechanisms for increasing blood pressure: the activity of the CNS and the renin-angiotensin – aldosterone system, volume-dependent mechanisms. There are various combinations of antihypertensive drugs. Combinations of two anti-hypertensive drugs are divided into rational (effective), possible and irrational. All the benefits of combination therapy are found only in rational combinations of antihypertensive drugs. These include: ACE inhibitor + diuretic; ARA + diuretic; IAPF + AK; ARA + AK;dihydropyridine AK + β-AB; AK + Diu retic; β-ab + diuretic .
There are certain nuances of combination therapy. It can be of two types: starting monotherapy with a transition to a combination therapy in the absence of an effect (i.e. achieving the target level of blood pressure) or a combination therapy at the start of treatment . If you start from the strategy of starting monotherapy, then the doctor inevitably faces a situation of painstaking search for the most optimal antihypertensive agent for the patient with frequent changes drugs and their dosages, which often deprives the doctor and the patient of confidence in success and, ultimately, reduces adherence to treatment. This is especially true for patients with mild and moderate hypertension, most of whom do not experience discomfort from an increase in blood pressure and are not motivated to treat. Combined therapy at the start of treatment, provided effective doses of the drugs allow for faster adequate blood pressure control in most cases of hypertension.
The most popular in Russia is the combination of an ACE inhibitor and a diuretic. As the results of the Pythagoras study show, almost a third of physicians in Russia prefer the combination of these particular drugs . It is possible that these two classes of drugs provide control of almost all mechanisms for increasing blood pressure. Fixed combinations of antihypertensive drugs, which are significant but increase patients’ commitment to the treatment of hypertension. Among the fixed combinations, noliprel and noliprel-forte (2–4 mg of perindopril and 0.625–1.5 mg of indapamide), korenitek (20 mg of enalapril and 12.5 mg of hypothiazide), tarka (180 mg of isoptin CP) are successfully used. and 2 mg of trandolapril). At the same time, fixed combinations of drugs limit titration of doses, if necessary, both upwards and downwards. Therefore, the emergence of the first non-fixed combination Enzix containing two drugs in one blister – enalapril and indapamide is important. The drug owes its appearance to the EPIGRAF project, which was carried out under the auspices of the All-Russian Scientific Society of Cardiology (coordinator Academician of the Russian Academy of Sciences Yu.N. Belenkov). The project consisted of two multicenter studies, EPIGRAF-1 and EPIGRAF-2.
A doctor and 38 polyclinics from 17 cities took part in the open study of EPIGRAPH-1 . A total of 550 patients with grade II – III hypertension (baseline systolic blood pressure> 160 mmHg) were included in the study, and among them were patients not only with essential, but also with symptomatic hypertension. A special feature of the study was that already at the beginning of treatment patients were prescribed a combination of enalapril and indapamide. Moreover, if the dose of indapamide was constant – 2.5 mg, then the dose of enalapril varied depending on the initial level of blood pressure. At the same time, doctors had the possibility of adjusting the doses of enalapril depending on the achievement of the target blood pressure within 4 weeks. As a result of the treatment of hypertensive patients with differentiated doses of enalapril and indapamide, a significant reduction in both systolic and diastolic blood pressure was achieved. At the same time, target BP was achieved in 70% of patients (<140/90 mmHg).The percentage of patients who responded to treatment in general (decrease in systolic and diastolic blood pressure –∆20 / 10 mm Hg) was 77.1. Adverse reactions were observed in only 8.2% of patients. Only 2.7% of patientsntov was a cough . The main conclusion of the study was that efficacy and safety The combination of enalapril with indapamide in the treatment of hypertension did not depend on gender, age, and the cause of the increase in blood pressure (primary hypertension or secondary hypertension of renal origin). It is especially necessary to pay attention to the latter circumstance, in connection with the ingrained opinion that the effectiveness of antihypertensive therapy in patients with symptomatic hypertension decreases. The combination of enalapril with indapamide was especially preferred in women, in whom the ACE inhibitor monotherapy may be less effective. The results of the EPIGRAPH-1 study allowed us to work out the most effective doses of enalapril and indapamide for hypertensive patients of varying degrees, which became the basis for the creation of 3 types of Enzix preparation: Enzixil – 10 mg of enalapril and 2.5 mg of indapamide (single dose in the morning) for hypertensive patients I degree; Enzix Duo – 10 mg enalapril and 2,5 mg of indapamide (in the morning) + 10 mg of enalapril (in the evening) for patients with hypertension of II degree; Enzaprim Enzapi Duo Forte – 20 mg of enalapril and 2.5 mg of indapamide (in the morning) + 20 mg of enalapril (in the evening).
The effectiveness and safety of the Enzix was evaluated in the study EPIGRAF-2, which by design was a comparative, randomized multicenter, which included 9 centers in Russia and 1 center in Serbia . A total of 313 patients were included in the study, which were randomized into two groups. The Enzix group included 211 patients, the control group included 102 patients.
In the control group, treatment was carried out with antihypertensive drugs of any class, except for ACE inhibitors and diuretics.
This study also confirmed the high efficacy of the combination of enalapril and indapamide. In the group receiving Enzix – 72.5% of patients reached the target level of blood pressure. Thus, the early initiation of treatment of patients with hypertension of grades I – II with the unstable combination of enalapril and indapamide (Enzix), in comparison with routine antihypertensive therapy, makes it possible to achieve normalization of blood pressure more often. In addition, Ensix therapy is cost effective.
The presence of a diuretic of indapamide in the Enzix composition without undesirable side effects is of significant clinical importance. As already noted, diuretics and BB (especially non-selective) have a negative metabolic effect and increase the risk of diabetes.
This fully applies to combination therapy. In this regard, the components of the drug Enzix do not cause concern. Enalapril, as an ACE inhibitor, is by definition metabolically neutral, and indapamide occupies a special place among diuretics. At the recommended doses (1.5–2.5 mg per day), it not only provides an adequate antihypertensive effect, but is also metabolically neutral. It has been proven that indapamide does not cause hypokalemia, changes in the carbohydrate  and lipid profile . Especially convincing evidenceThe metabolic neutrality of indapamide was obtained as a result of a meta-analysis of three studies involving a total of 1195 patients. According to the results of treatment with the retard form of indapamide for 9–12 months, no effect on the carbohydrate and lipid profile, as well as the level of uric acid was found .
Indapamide, in addition to the diuretic effect, has a vasodilating effect by reducing the sodium content in the artery wall, regulating calcium intake in vascular smooth muscle cells, as well as increasing the synthesis of prostaglandin E2 in the kidneys and prostacyclin in the endothelium . Thus, indapamide, having a more pronounced effect on the vessels than the other diuretics, affects endothelial function. It has an antioxidant effect, increasing the bioavailability of NO . Moreover, the LIVE study proved that indapamide therapy can cause regression of hypertrophy and left ventricular myocardium .
The presence of 2 antihypertensive drugs in a single double blister will certainly help to increase adherence to treatment. Three different dosages of Enzix will contribute to the adequate selection of non-fixed combination in various clinical situations related to the degree of increase in blood pressure.
In the concept of a multifactor approach, the most important is the correction of lipid metabolism disorders, which, as already mentioned, makes the most important contribution to the risk of complications. By impaired lipid metabolism, we mean an increase in the level of total cholesterol (cholesterol), cholesterol cholesterol of low-density lipoproteins (LDL), triglycerides (TG), and a decrease in cholesterol cholesterol of high-density lipoproteins (HDL). In large epidemiological studies, a direct relationship was found between cholesterol level and mortality from coronary heart disease [71,72], and also that a decrease in the level of LDL cholesterol leads, in turn, to a decrease in the risk of developing coronary heart disease [73,74]. Today, the most effective and safest drug-based lipid-lowering therapy is statins. They reduce LDL cholesterol by 20–60%, TG – by 10–40%, and HDL cholesterol increases by 5–15% . Prolonged use of statins leads to a significant reduction in the risk of cardio and cerebrovascular complications . At the same time, the effectiveness of statins has been proven not only in patients with coronary artery disease, but also without coronary artery disease. The ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm) study proved the effectiveness of statins for the prevention of cardiovascular complications in patients with hypertension and moderate hypercholesterolemia . This fact is reflected in the recommendations of GFCF for the diagnosis and treatment of atherosclerosis, where statin administration is recommended not only for treating patients with various clinical manifestations of atherosclerosis, but also for treating patients without clinical manifestations of atherosclerosis and with a high risk of CVD death according to the SCORE scale. Thus, indications for lipid-lowering therapy are greatly expanded, as a means of not only secondary, but also primary prophylaxis.
At the same time, statins have a number of additional pleiotropic effects, which include the ability to improve endothelial function, reduce blood viscosity, and also have an anti-inflammatory, hypotensive effect. One of the most important effects of statins is an improvement in endothelial function [78,79]. It is with the improvement of endothelial function in the application of statins that their hypotension effect has been identified, which has been identified in a number of studies in recent years [80,81]. In this regard, the data of our own double-blind, randomized, placebo-controlled clinical study are of interest, the purpose of which was to study the hypotensive effect of pravastatin in patients with mild hypertension and HCS. The 12-week study included 52 male patients aged 35–60 years,who were randomly assigned to 3 groups. Group I received a placebo – 16 people, Group II – Pravastatin – 40 mg per day – 18 people and Group III – prolonged non-dihydropyridine calcium antagonist – diltiazem (altiazem PP ® ) – 180 mg per day – 18 people.
The treatment with pravastatin showed a significant decrease in the average daily GAD by 6.2 mm Hg. (p <0.001), the average daily dad – 5.4 mm Hg. Art. (p <0.001). At the same time, against the background of receiving a placebo, there was no change in the average daily GARDEN (total –0.1 mm Hg, p> 0.05), nor the average daily DBP (total –0.3 mm Hg. Art. , p> 0.05). At the same time, pravastatin provided a significant reduction in the average daily GARDEN and DBP compared with placebo. At the same time, it was slightly inferior in its hypotensive effect.
As for the hypolipidemic effect of pravastatin, the decrease in total cholesterol was 29.2 ± 3.3% of the initial level (p <0.001), LDL cholesterol – 37.7 ± 4.4% of the initial level (p <0.001) , increase in HDL cholesterol levels – 30.1 ± 5.7% from the initial level (p <0.001).
Interestingly, the degree of decline in cholesterol levels did not correlate with the degree of decline in either GARDEN or DBP. Thus, the hypotensive effect of pravastatin was not dependent on its hypolipidemic action.
Pravastatin’s hypotensive effect made an additional contribution to reducing the total coronary risk, calculated on the basis of the computerized model of the West German study PROCAM STUDY . The main components of this formula are: age, CAD, level of total cholesterol or LDL cholesterol, HDL cholesterol, TG, smoking status, type 2 diabetes, history of coronary artery disease, myocardial infarction, history of coronary artery disease.
Taking into account only the hypolipidemic effect, the total risk was significantly reduced (–69%) and amounted to 7.2%, while taking into account the hypotensive effect, it reached 6.3%. Thus, the antihypertensive effect of pravastatin makes an additional contribution to the reduction in total coronary risk .
Perhaps the additional antihypertensive effect of pravastatin, which is a consequence of the improvement in endothelial function, can be attributed to the WOSCOPS (West of Scotland Coronary Prevention Study) study on primary ischemic heart disease prevention, where the efficacy of pravastatin in the treatment of 6550 people with lipid metabolism disorders was evaluated  . The reduction in coronary risk (combined endpoints – nephatal MI, coronary artery disease, coronary angioplasty, CABG) was significantly higher (by 12%) than expected, calculated on the basis of the Framingham model, which takes into account the level of total cholesterol.
With long-term statin therapy, it is necessary to take into account not only their hypopidemic effect, but also the hypotensive effect, which makes an additional contribution to the reduction in total coronary risk.
Since endothelial dysfunction is the cause of the disruption of the structure and normal functioning of the vessels of the microvasculature , it would be logical to assume that statins have a favorable effect on the microcirculation system, which is the basis for adequate organ and tissue perfusion. There are only a few data from foreign studies on the effect of statins on microcirculation. . No studies on this topic have been conducted in Russia. We have undertaken a study to study the effect of a new statin called Rosuvastatin (Crestor, AstraZeneca, UK) on the microcirculatory bed in patients with dyslipidemia and mild and moderate hypertension. The study involved 25 patients with cholesterol levels above 5.0 mmol / l and LDL cholesterol above 3.0 mmol / l and the level of the GARDEN 140–179 mm Hg. and dad 90–109 mm Hg For 12 weeks, patients took 10 mg of rosuvastatin without dose adjustment. The state of the microcirculatory bed was studied using laser Doppler flowmetry.
In general, the favorable effect of rosuvastatin on the microcirculatory bed has been established. At the same time, positive shifts were observed in various pathological types of microcirculation – in spastic and hyperemic. In the case of the spastic type of microcirculation, when the microcirculatory bed is depleted in blood, an increase in blood flow occurs during the treatment with Krestor, as evidenced by the increase in the microcirculation index. The same is evidenced by the decrease in the reserve of capillary blood flow (RSC), which is a consequence of the increase in the number of functioning capillaries. In the hyperemic type of microcirculation, when there is an overflow of the vascular bed, there is a decrease in blood flow, as evidenced by a decrease in the microcirculation index. In these patients, an increase in RCC is observed, which plays a positive role, since it facilitates unloading of the overfilled precapillary link.
At the same time, in both groups, a decrease in peripheral vascular resistance was observed, as evidenced by a significant increase in myospheric amplitudes. As a result, blood flow to the capillaries increases and organ and tissue perfusion improves.
Thus, in general, during the treatment with Crestor, patients with DLP and mild and moderate hypertension have seen favorable changes in the microcirculation system.
Another positive effect of rosuvastatin on the vessels was also revealed – a significant decrease in the SBP – by 8 mm Hg. Art., DBP – at 6 mm Hg. Art.
The study confirmed the pronounced hypolipidemic effect of Crestor.
Thus, the new hypolipidemic drug rosuvastatin has not only a pronounced hypolipidemic effect, but also a positive effect on the vessels, contributing to microcirculation and a decrease in blood pressure in patients with dyslipidemia and mild and moderate arterial hypertension . Of course, the indicated vascular effects of Crestor can positively affect the effectiveness of the prevention of CCO during long-term therapy with this statin.
As already noted, the problem of control of blood pressure and the correction of concomitant risk factors in the case of patients without clinical manifestations of atherosclerosis is that patients are not motivated for drug treatment (“risk factors do not hurt”), not to mention the motivation for non-pharmacological methods for the correction of concomitant risk factors. In this regard, one should note the successful experience of holding educational schools (in Ivanovo, Khabarovsk), which indicate that achieving better control not only of blood pressure, but also of correcting risk factors is quite possible .
Of particular note is the relevance of the development and implementation of motivational technologies in clinical practice. One of them can be the electronic version of SCORE (Systematic Coronary Risk Evaluation – Systematic (regular) coronary risk assessment) – a new system for assessing the risk of fatal outcomes of CVD for 10 years, developed by experts of the European Society of Cardiology together with specialists of the Federal Research Center The Ministry of Health and Social Development of Russia based on data from prospective studies conducted in European populations, including Russian (in total, more than 200,000 people). This The interactive system allows you to visually demonstrate to the patient the risk of a fatal outcome from CVD within 10 years and its positive dynamics in reducing the risk as a result of the intervention. Such a visual computer demonstration is designed to increase the motivation and commitment of patients to the drug and non-drug correction of risk factors and, ultimately, lead to a significant decrease in MDR. Currently, the Russian version of HeartScore has appeared on the Internet, which can be used by practical doctors.
The SCORE system includes the following risk factors: gender, age, smoking, systolic blood pressure (MAP), total cholesterol level. The high-risk criterion was defined as a risk of 5% and higher, in contrast to the previous figure of 20% and higher.
The status of smoking is determined when the patient is asked if he answers “yes” or “no”. A patient is considered to be a smoker if he smokes more than seven cigarettes a week.
The risk is considered very high if, when the patient data is projected onto the SCORE card, it is higher than 10%; high – if it is in the range from 5 to 10% medium – from 2 to 4% and low – less than or equal to 1%.
In case of high and very high risk, the patient needs to take active preventive and therapeutic measures aimed at eliminating and correcting risk factors.
Compared to the risk table, the advantages of using HeartScore for clinicians and patients are in their speed and ease of use, individual adaptation to the patient. The program offers:
. – graphic demonstration of absolute cardiovascular risk,
. – assessment of the relative role of corrected risk factors,
. – recommendations of intervention that contributes to a change in the behavior of treatment tolerance, i.e. patient adherence to treatment. HeartScore ® is a primary prevention tool for CVD, for assessing the risk of those who are not yet sick. But patients with existing symptoms of diseases associated with atherosclerosis require intensive treatment to prevent complications, so in such cases there is no need to resort to such a risk assessment, because these patients are already at high risk. HeartScore ®helps to assess the risk, and does not pretend to the absolute accuracy of the forecast. In HeartScore task ® It does not include an influence on the decision of the doctor regarding the tactics of treatment of patients and the starting point of treatment (from what level of risk to start treatment). These questions undoubtedly remain in the competence of the doctor.
In accordance with the European recommendations for the prevention of CVD, treatment should begin if the risk of death from CVD within 10 years exceeds 5%. For young patients, it is necessary to focus on the relative risk table. We have conducted a multicenter large-scale study on the effectiveness of integration into the clinical practice of the electronic version of SCORE. . The study involved 350 therapists from 47 cities of Russia. Each therapist included 3 high-risk patients with hypertension in the study (risk on the SCORE scale> 5%). A total of 1050 patients were included in the program. For the first time in the practice of research, not only in Europe, but also in Russia, the electronic version of SCORE was used to study the effect of its use in order to increase adherence to medical treatment of hypertension and effective control of associated risk factors. For this purpose, a subsample of 128 patients with AH was formed. In these patients, the risk was assessed using the electronic version of SCORE. Patients (n = 481 people) matched for age, sex, systolic blood pressure, frequency of smokers, body mass index were selected as the control group.In the control group, patients were shown a risk assessment according to the usual SCORE table. All patients were prescribed combination antihypertensive therapy as a starting therapy. The study lasted 1 year. By the end of the study, in the main group, a significantly larger number of patients reached the target level of blood pressure or responded to treatment (decrease in the GARDEN not less than 20 mm. Mercury. And / or decrease in DBP not less than 10 mm. Mercury. with a group of patients whose total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.All patients were prescribed combination antihypertensive therapy as a starting therapy. The study lasted 1 year. By the end of the study, in the main group, a significantly larger number of patients reached the target level of blood pressure or responded to treatment (decrease in the GARDEN not less than 20 mm. Mercury. with a group of patients whose total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.All patients were prescribed combination antihypertensive therapy as a starting therapy. The study lasted 1 year. By the end of the study, in the main group, a significantly larger number of patients reached the target level of blood pressure or responded to treatment (decrease in the GARDEN not less than 20 mm. Mercury. with a group of patients whose total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.By the end of the study, in the main group, a significantly larger number of patients reached the target level of blood pressure or responded to treatment (decrease in the GARDEN not less than 20 mm. Mercury. with a group of patients whose total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.By the end of the study, in the main group, a significantly larger number of patients reached the target level of blood pressure or responded to treatment (decrease in the GARDEN not less than 20 mm. Mercury. with a group of patients whose total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.compared with the group of patients in whom the total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.compared with the group of patients in whom the total risk was assessed according to the tables (without using the electronic version of SCORE), which corresponded to 90% to 82% of patients in the main and control group (p <0.005), Fig. 13. Thus, a more pronounced decrease in total cardiovascular risk was achieved in those patients whose risk was assessed using the electronic version of SCORE.
These data indicate the feasibility of introducing into clinical practice the management of patients without clinical manifestations of atherosclerosis of the electronic version of SCORE, not only as a tool for assessing the overall risk, but also as a motivational technology to improve adherence to drug and non-drug risk control methods. Ultimately, this should lead to a more effective reduction in total cardiovascular risk.
- Hypotension is diagnosed if systolic blood pressure does not exceed 90 mm Hg. Art.
- Shock is a clinical syndrome characterized by, in addition to hypotension, signs of reduced perfusion of peripheral tissues (cold skin, oligoanuria, lethargy and lethargy).
- Breathing with 100% oxygen through a mask with a non-reversible valve and a bag-tank at an oxygen supply rate of 5–6 l / min).
- To correct the pumping function of the left ventricle, blood pressure should be initially normalized. In case of arterial hypotension / cardiogenic shock, it is initially necessary to make sure that the ventricles of the heart are sufficiently filled with pressure (no absolute or relative hypovolemia). In an emergency in the absence of pulmonary edema, it is advisable to quickly inject 250 to 500 ml of fluid intravenously, possibly repeatedly (by controlling the degree of stagnation in the lungs and, if possible, at least central venous pressure). If a sufficient increase in blood pressure is not achieved, infusion of a pressor agent should be initiated, the choice of which depends on the level of blood pressure. In the presence of hypovolemia, it is important to identify and, if possible, eliminate its cause. In cases where pulmonary edema is combined with increased blood pressure, it is necessary to reduce it by infusion of nitroglycerin or sodium nitroprusside.To correct myocardial contractility, other existing disorders should also be eliminated (hypoxia, hypoglycemia, drug overdose). In addition, rapid restoration of normal myocardial blood supply (thrombolytic therapy or invasive methods of myocardial revascularization during occlusion of a large epicardial coronary artery), as well as surgical correction of existing intracardiac hemodynamics, may be required.as well as surgical correction of existing intracardiac hemodynamic disorders.as well as surgical correction of existing intracardiac hemodynamic disorders.
- The norepinephrine infusion rate is 0.5–30 mcg / kg / min, the dopmin infusion rate is 2.5–20 mcg / kg / min.
- Simultaneous (but not isolated infusion of dobutamine) is possible. Dobutamine is the drug of choice for myocardial infarction of the right ventricle (it is also important to administer intravenous fluids, not using vasodilators and diuretics).
- Dobutamine infusion rate 2–20 mcg / kg / min.
- Perhaps the use of intra-aortic balloon contraception (considered as a temporary measure before conducting invasive interventions – myocardial revascularization using angioplasty procedure, coronary artery bypass surgery, surgical correction of intracardiac hemodynamics, heart transplantation).
- For the correction of high blood pressure in the acute phase of myocardial infarction, nitroglycerin is preferable, and in the absence of myocardial ischemia, sodium nitroprusside is preferable.
- First-line interventions, in addition to intravenous administration of morphine and a diuretic (furosemide), also include giving the patient a half-sitting position with his legs down and ensuring breathing with 100% oxygen. With systolic blood pressure above 100 mm Hg. Art. you should start taking nitroglycerin (1 tablet every 5 to 10 minutes) or isosorbiddinitrate as an aerosol until it is possible to administer intravenous infusion of nitroglycerin. If there is no response to the first dose of furosemide, a double dose should be administered within 20 minutes. A ventilator should be started when the arterial blood oxygen saturation drops to 90%, the oxygen tension in the arterial blood reaches 60 mm Hg. Art. when breathing 100% oxygen, as well as clinical manifestations of brain hypoxia (drowsiness, lethargy), a progressive increase in the voltage of carbon dioxide in the blood or an increase in acidosis.In milder cases, it is possible to evaluate the effectiveness of creating a positive pressure at the end of exhalation or breathing under constant positive pressure.
- Intravenous nitroglycerin is assigned to second-line drugs due to the time lag before the start of treatment. The administration of positive inotropic agents (dobutamine in the absence of arterial hypotension and dopmine in its presence) is assigned to the same group of interventions.
- Amrinone as a positive inotropic agent and a vasodilator is administered at a loading dose of 0.75 mg / kg for 2–3 minutes followed by an infusion of 5–15 µg / kg / min. Euphyllinum is administered with severe bronchospasm at a loading dose of 5 mg / kg in 20-30 minutes, followed by an infusion of 0.5-0.7 mg / kg / h. Its use should be avoided with supraventricular tachyarrhythmias. Intra-aortic balloon contraception is considered as a temporary measure before invasive interventions (myocardial revascularization using an angioplasty procedure, coronary artery bypass surgery, surgical correction of intracardiac hemodynamics, heart transplant).