Combination Antihypertensive Therapy In Patients Research Articles

Efficacy of combined antihypertensive therapy in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease with various polymorphisms of the CYP2C9 gene

Background. The difficulty of achieving target blood pressure (BP) levels in patients with arterial hypertension (AH) is often due to their type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). In turn, taking into account the individual genetic characteristics of the body helps to personalize treatment and make it more effective. Aim. To compare the antihypertensive efficacy of a fixed combination of amlodipine and olmesartan medoxomil (Aml/Ol-M) in patients with hypertension and T2DM, with and without NAFLD, depending on the polymorphism of the CYP2C9 gene. Materials and methods. The study included 139 patients with uncontrolled hypertension and concomitant T2DM; after diagnosis of NAFLD, they were randomized into 2 groups: without NAFLD (group 1, n=70), with NAFLD (group 2, n = 69). After discontinuation of previous ineffective antihypertensive therapy, they were prescribed a combination of Aml/Ol-M in doses of 5-10/20-40 mg/day. At baseline, 4, 8, 12 and 24 weeks, their office BP levels were determined; Also, at the initial visit and after 24 weeks of treatment, the main indicators of 24-hour blood pressure monitoring (ABPM) were measured. Patients who did not reach the blood pressure target within 12 weeks of therapy were excluded from the study. Those who continued to participate in the amplifierThe Rotor Gene-Q allele discrimination method revealed the following distribution of polymorphic variants of the CYP2C9 gene: *1/*1 was found in 52 and 47, *1/*2 – in 6 and 5, *1/*3 – in 5 and 6 subjects, for groups 1 and 2, respectively. Results. The initial levels of office BP values were significantly higher in patients of group 2 and amounted to 153,5 mm Hg for systolic and 93 mm Hg for diastolic blood pressure, compared with 145 mm Hg and 88 mm Hg those included in group 1. After 12 weeks of therapy, the achievement of target blood pressure was registered in 63 (90 %) patients of group 1 and in 58 (84,1 %) of group 2. After 24 weeks of observation, in both groups a beneficial effect of the studied combination of drugs on all indicators of ABPM was noted, but a more pronounced improvement was noted in patients with NAFLD. Along with this, significant improvements in daily blood pressure profiles were registered in both groups 1 and 2: an increase in the number of patients with the “dipper” profile and a decrease in the number of patients with the pathological “non-dipper” profile. The antihypertensive effectiveness of Aml/Ol-M has been demonstrated for all isolated allelic variants of the CYP2C9 gene. Conclusions. A 24-week study with the use of Aml/Ol-M demonstrated a high incidence of achieving office BP target values in patients with hypertension and T2DM, with and without NAFLD. However, a more pronounced decrease in ABPM levels was found in patients with NAFLD. Carriage of any of the identified polymorphic gene variantsCYP2C9 had no effect on the clinical effects of the studied combination.

“The impact of statins addind to the fixed combination antihypertensive therapy on the arterial stiffness in patients with moderate and severe hypertension"

AimThe objective of this study was the evaluation of the arterial stiffness, which changed after adding statins to the guidelines recommended dual or triple fixed combination antihypertensive therapy in patients with moderate to severe arterial hypertension. Materials and methodsIt was included 99 patients in total being diagnosed with moderate and severe arterial hypertension (2nd and 3rd stages of arterial hypertension) without diabetes. Those patients were divided into 2 groups. The first group (n = 59) was assigned to the dual or triple fixed combination antihypertensive therapy plus including statins.Patients in the second group (n = 40) received only the dual or triple fixed combination antihypertensive treatment following the recommended guidelines without any statins. The CAVI index was performed in order to measure in all participants before and at the end of the follow-up period. Furthermore, the Office (Clinic BP) Blood Pressure (BP) was monitored in assigned participants as well as the Ambulatory Blood Pressure Monitoring (ABPM). The laboratory investigations also took place such as the standard blood test, the urine and biochemistry analysis and the estimated Carotid Intima-Media Thicknesses with Ultrasound. The study-duration was 6 months. ResultsOffice BP and ABPM had decreased significantly and equally in both treatment groups. The total cholesterol (TC) and LDL cholesterol had decreased significantly in the statin group on 1,76 mmol/l (30%, p < 0,05) and 1,51 mmol/l (41%, p < 0,05) respectively. In the group without statin therapy, there was no changes in the level of TC and LDL cholesterol. In the group without statins, it was noted a significant decrease in the level of BP, however, the CAVI index level was shown the growth to +0,9 units on the right side and +1,0 units on the left.In the group without statin's treatment, the CAVI index was changed from 7.73 ± 0.17/7.62 ± 0.19 units to 8.63 ± 0.22/8.62 ± 0.12 units on the right/left site after treatment (p < 0,05). It means there was an increase in the stiffness of the arterial wall in terms of cardio-vascular index CAVI in the group without added statin after 6 months of the therapy. In the group with added statin after 6 months of the therapy, the CAVI had not have any changes. It can be seen from the observed figures: the CAVI on the right/left site was 8.32 ± 0.16/8.33 ± 0.19 initially and 8.44 ± 0.16/8.24 ± 0.15 units treatment (p > 0,05) afterwards.We did not note any impact of statin therapy on the BP level. However, a significant correlations was found between the CAVI index with age and the serum level of blood Triglycerides before treatment, including LDL Cholesterol and HDL Cholesterol, duration of hypertension, the blood glucose level, the Potassium level and the Maximum Thickness of Intima-Media of Carotid Arteries in the statins group. ConclusionThe adding of the statin to the current fixed dual or triple combination of the antihypertensive therapy could prevent the progression of arterial stiffness in patients with 2nd and 3rd stages of arterial hypertension.

Blood pressure lowering effects of β-blockers as add-on or combination therapy: A meta-analysis of randomized controlled trials.

The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: -4.1 [-6.0, -2.2] and -3.7 [-4.6, -2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, -10.2 [-14.2, -6.2]; diastolic pressure, -5.4 [-8.2, -2.6]), CCBs (systolic pressure, -4.1 [-7.1, -1.0]; diastolic pressure, -2.8 [-4.1, -1.5]), and ACEIs/ARBs (systolic pressure, -2.9 [-4.3, -1.5]; diastolic pressure, -4.2 [-5.0, -3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, -1.3mm Hg [-5.8, 3.2]; diastolic pressure, -.3mm Hg [-2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, -3.6mm Hg [-5.9, -1.3]; diastolic pressure, -2.1mm Hg [-3.5, -.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs.

N-[2-(5-metoksi-1H-indol-3-il)]acetamid može da koriguje arterijsku hipertenziju kod ljudi koji imaju problema sa spavanjem

Introduction. Sleep disturbance is a frequent complaint of patients suffering from arterial hypertension (AH) for a long time. A hidden and uncontrolled increase in blood pressure (BP) makes the course of physiological processes more difficult, disrupts the regulation of biological rhythms, and increases the risk of cardiovascular complications even with a short duration of AH. At the same time, chronic sleep disorders contribute to the development of hypertension, defining the role of a new socially significant risk factor. An important role in the pathogenesis of insomnia is played by a deficiency in melatonin (MT) synthesis, which negatively affects the cardiovascular system (CVS). Aim. The aim of the paper was to study the features of central and vascular hemodynamics in patients with the 1st degree AH and to evaluate the clinical effectiveness of antihypertensive therapy with synthetic analog of prolonged-release MT at the onset of the disease. Methods. Instrumental examination included registration of an electrocardiogram, office measurement of blood pressure with an automatic tonometer, non-invasive automatic blood pressure monitoring for 24 hours. The severity of insomnia was assessed by somnological questionnaires. Representatives of the 1st group (n = 34) took monotherapy with the ACE inhibitor ramipril, participants of the 2nd group (n = 33) took the ACE inhibitor ramipril in combination with a synthetic analogue of melatonin. Results. The results of a randomized open prospective study including 78 participants reveal the activity of the renin-angiotensin-aldosterone system (RAAS), hypersympathicotonia at night and desynchronosis due to a possible deficiency in the MT secretion. Pharmacological antihypertensive therapy with the addition of prolonged release MT analog was accompanied by a significant improvement in the clinical condition of hypertensive patients. Positive dynamics of indicators of systemic hemodynamics and functional arterial parameters of stiffness was noted. Conclusion. The article describes the probable benefits of melatonin as part of combination antihypertensive therapy in patients with early-stage hypertension and insomnia. Additional introduction of MT at the onset of the AN as a physiological regulator of circadian biological rhythms is substantiated.

Clinical efficacy of combination therapy of arterial hypertension in patients with chronic glomerulonephritis with different blood pressure salt sensitivity

Arterial hypertension is the main factor in the progression of CKD of any etiology; therefore, effective antihypertensive therapy is a crucial task of healthcare practice. In this work, the authors aim to study the comparative effectiveness of various types of combined antihypertensive therapy in patients with different blood pressure salt sensitivity.

Choice of optimal antihypertensive therapy in patients with diabetes mellitus type 2

Aim of the study: to develop personalized approaches to combined antihypertensive therapy in patients with type 2 diabetes mellitus and arterial hypertension, depending on the parameters of the daily blood pressure profile and heart rate variability.Material and methods. We examined 322 patients with type 2 diabetes and arterial hypertension who had not previously received antihypertensive drugs on a regular basis. At the first stage, patients were prescribed Perindopril 10 mg per day and Indapamide retard 1,5 mg per day. In the absence of reaching target blood pressure (BP) levels after 28 days, a third antihypertensive drug was added — Amlodipine 5 mg per day, followed by titration to 10 mg 1 r per day (group I) or a b-blocker — Carvedilol at a dose of 12,5 mg 2 r per day, also followed by titration up to 25 mg 2 r per day (group II). Daily monitoring of BP and ECG was carried out, the average daily heart rate (HR), circadian index (CI), as well as heart rate variability were determined.Results and its discussion. Patients with type 2 diabetes have a high variability of blood pressure throughout the day, high pulse blood pressure, as well as a rigid circadian profile of heart rate. The appointment of a standard two-component antihypertensive therapy, including Perindopril 10 mg and Indapamide retard 1,5 mg per day, allows reaching the target blood pressure only in 46% of patients. The addition of amlodipine or carvedilol significantly increases the effectiveness of therapy, allowing more than 80% of patients to achieve the target blood pressure. At the same time, the use of amlodipine leads to a greater extent to a decrease in pulse pressure, and the inclusion of carvedilol improves the circadian profile of blood pressure and heart rate, and has a positive effect on heart rate variability.

Current Guidelines for the Treatment of Arterial Hypertension in Patients with Diabetes Mellitus and Chronic Kidney Disease

The current understanding of the management of patients with diabetes mellitus (DM) based on the concept of the cardiovascular continuum involves not only the prevention and treatment of cardiovascular diseases (CVD), but also the prevention and treatment of chronic kidney disease (CKD). The fact is that patients with DM and CKD represent a special group of patients with a very high risk of CVD and cardiovascular mortality. Such patients require early diagnosis and timely identification of risk factors for the development and progression of CKD for their adequate correction. Arterial hypertension, along with hyperglycemia, is the main risk factor for the development and progression of CKD in patients with diabetes. In this regard, the choice of antihypertensive therapy (AHT) in patients with diabetes is of particular importance. The basis of AHT in diabetes and CKD is the combination of a blocker of the renin-angiotensin-aldosterone system (an angiotensin-converting enzyme inhibitor [ACE inhibitor] or an angiotensin II receptor blocker [ARB]) and a calcium channel blocker (CCB) or a thiazide / thiazide-like diuretic. The task of the performed AHT is to achieve the target level of blood pressure (BP). At the same time, the optimal blood pressure values in patients with diabetes and CKD are blood pressure values in the range of 130-139/70-79 mm Hg. If the target blood pressure is not achieved, it is necessary to intensify antihypertensive therapy by adding a third antihypertensive drug to the therapy: CCB or a diuretic (thiazide / thiazide-like or loop). In case of resistant hypertension, it is necessary to consider the possibility of adding antagonists of mineralocorticoid receptors, other diuretics or alpha-blockers to the conducted AHT. Beta-blockers can be added at any stage of therapy if the patient has exertional angina, a history of myocardial infarction, atrial fibrillation, and chronic heart failure. The need to normalize blood pressure parameters by prescribing combined antihypertensive therapy in patients with diabetes and CKD is explained by a decrease in renal and cardiovascular risks, and, therefore, a decrease in the risk of mortality in this cohort of patients.

Combined antihypertensive and psychocorrective therapy in patients with arterial hypertension and anxiety-depressive disorders: are there any advantages?

Relevance. Arterial hypertension (AH) and anxiety-depressive disorders (ADD) are comorbid pathologies that are common in clinical practice. At the same time, the possibility of including an antidepressant in antihypertensive therapy for optimal control of hypertension, as well as to ensure a vasoprotective effect, has not been studied enough.&#x0D; Aim. To compare the effect of traditional antihypertensive therapy and therapy, including an antidepressant, on indicators of the daily profile of blood pressure (BP), stiffness of the vascular wall and central aortic pressure (CAP), the severity of anxiety and depression, as well as on cognitive function (CF) in patients AH and ADD.&#x0D; Materials and methods. The study included 90 patients with AH and ADD, who were randomized into two groups: group 1 patients who received a fixed combination of an angiotensin II receptor blocker and a diuretic, a b-blocker and an antidepressant; group 2 persons who took only three-component antihypertensive therapy. Before and after 24 weeks, all patients underwent a general clinical examination, 24-hour BP monitoring ABPM (BpLab Vasotens, Petr Telegin, Russia) with an assessment of the daily profile of BP, CAP and vascular stiffness. In addition, testing was carried out on the HADS, CES-D scales; CF were rated according to the Montreal scale.&#x0D; Results. In the group of patients treated with an antidepressant, it was noted that the target BP level was achieved more quickly when lower doses of angiotensin II receptor blockers were prescribed. After 6 months of therapy in both groups, there was a comparable positive dynamics of the main indicators of ABPM. In group 1, a statistically more pronounced decrease in both peripheral and CAP at night was recorded. In both groups of patients, a decrease in the augmentation index was noted; however, a statistically significant improvement in the parameters of the speed of propagation of the pulse wave in the aorta and the time of propagation of the reflected wave was recorded only in persons receiving antidepressant. In group 1, there was a regression of ADD, as well as a significant improvement in CF.&#x0D; Conclusions. The use of sertraline as part of a combination antihypertensive therapy in patients with AH and ADD contributed to a more rapid achievement of target BP values, a significant improvement in ABPM (especially at night), vascular wall stiffness and CAP. It is also important that the appointment of sertraline was accompanied by a regression of anxiety-depressive symptoms, an improvement in CF.

Efficacy of a fixed-dose combination (amlodipine/losartan) in the treatment of a patient with arterial hypertension, dyslipidemia and obesity

The article substantiates the feasibility of combination antihypertensive therapy in patients with arterial hypertension without target organ damage and high cardiovascular risk. The authors consider a clinical case of the use of amlodipine and losartan in a fixed-dose combination (Lozap AM) as part of complex therapy in a patient with arterial hypertension, dyslipidemia and obesity. The clinical case showed the ability of the drug to both achieve a steady level of target blood pressure and improve its daily profile by transferring the Night-peaker type to the Non-dipper type.

Как повысить эффективность комбинированной терапии артериальной гипертензии у больных с сопутствующей хронической обструктивной болезнью легких?

Aim: to conduct a comparative assessment of the hypotensive effect, as well as the effect on endothelial function, oxidative stress, and pulmonary artery pressure of chlorthalidone and hydrochlorothiazide as part of combined antihypertensive therapy in patients with arterial hypertension (AH) in combination with chronic obstructive pulmonary disease (COPD).Patients and Methods: the prospective study included 66 patients divided into two groups. As the main antihypertensive therapy, group 1 was prescribed with a combination of azilsartan medoxomil 40 mg and chlortalidone 12.5 mg as a fixed combination of Edarbi® CLO. Group 2 received a free combination of azilsartan medoxomil 40 mg (Edarbi®) and hydrochlorothiazide 12.5 mg. All patients underwent 24-hour blood pressure monitoring: (ABPM), echodopplercardiography, endothelium-dependent vasodilation, lipid peroxidation (LPO), nitric oxide metabolites, and endothelin-1 levels at baseline and after 6 months of treatment. Results: target blood pressure values (&lt;130/80 mm Hg) were achieved in 91% of patients in group 1, and 51.5% in group 2 after 1 month of the study. After 6 months of treatment, all patients in both groups reached the target BP values, but in group 2, the dose of hydrochlorothiazide had to be increased to 25 mg. According to the ABPM data, after 6 months of treatment, group 1 showed a decrease in the morning surge in SBP by 7.0±2.1% and DBP by 10±7.3%. There was also an increase in the number of patients with the daily profile of «dipper» type to 78.8%. In group 2, there was a decrease in the morning surge in SBP by 6.3±5.9% and DBP by 4.8±4.6% after 6 months of treatment. There was an increase in the number of patients with the daily profile of «dipper» type to 36.4%. After 6 months of treatment, there was more pronounced improvement in laboratory parameters of group 1 characterizing endothelial dysfunction and oxidative stress. Statistically significant results were obtained for conjugated trienes, NO2, S, Imax, and endothelin-1 when comparing groups 1 and 2.Conclusion: treatment of AH in patients with concomitant COPD in the form of a fixed combination of azilsartan medoxomil and chlorthalidone versus free combination of azilsartan medoxomil with hydrochlorothiazide has a more pronounced antihypertensive effect, positively affecting the daily BP profile, pulmonary artery pressure, endothelial function and lipid peroxidation processes after 6 months of treatment.KEYWORDS: arterial hypertension, chronic obstructive pulmonary disease, endothelial dysfunction, lipid peroxidation, azilsartan medoxomil, chlorthalidone.FOR CITATION: Grigorieva N.Yu., Samolyuk M.O., Sheshina T.V. et al. How to improve the effectiveness of combination therapy of arterial hypertension in patients with concomitant chronic obstructive pulmonary disease? Russian Medical Inquiry. 2020;4(7):418–424. DOI: 10.32364/2587-6821-2020-4-7-418-424.

The effectiveness of combination antihypertensive therapy in patients with arterial hypertension and additional risk factors: obesity and obstructive sleep apnea syndrome.

To study the effectiveness of a fixed combination of perindopril and amlodipine, with the subsequent addition of indapamide-retard in male patients with arterial hypertension (AH), obesity and severe sleep apnea (OSAS). The study included 43 male patients in whom antihypertensive therapy titration was performed to achieve target blood pressure values with a fixed combination of calcium antagonist amlodipine (10 mg) and an angiotensin-converting inhibitor perindopril (5-10 mg) and indapamide-retard. At baseline and after 4-6 weeks, the effectiveness of antihypertensive therapy was monitored according to clinical measurements and ambulatory blood pressure monitoring (ABPM). An assessment of the carotid-femoral pulse wave velocity (cfPWV), aortic PWV (aoPWV), and ankle-brachial PWV (abPWV) was performed. Target blood pressure values (according to clinical blood pressure, 24-hour blood pressure monitoring) during therapy with amlodipine 10 mg and perindopril 10 mg reached 65% of patients and another 30% reached target blood pressure when adding indapamide-retard 1.5 mg, that is - 95% of all patients included in the study. Upon reaching the target blood pressure values, a significant decrease in cfPWV, aoPWV and abPWV was observed. The fixed combination of perindopril arginine and amplodipine, with the addition of indapamide retard in male patients with hypertension 1st degree in the presence of obesity and severe OSAS allows to reach effective control of blood pressure and improve the elastic properties of large arteries, which can lead to a favorable organoprotective effect in this category of patients.

Pharmacokinetic Approach Towards Personalization of Antihypertensive Pharmacotherapy

The current study was aimed at assessing an impact of oxidative phenotype on intensity of pharmacodynamics effect after applying a combination anti-hypertensive therapy in patients with high- and very high-risk arterial hypertension. It was confirmed that the level of decrease arterial pressure directly correlated with oxidative phenotype. Upon that, patients with slow oxidative phenotype administered with a fixed- vs. free-combination of amlodipine and lisinopril (Equator) exhibited significantly more pronounced anti-hypertensive effect.

EFFICIENCY OF COMBINED ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION AND OBESITY DEPENDING ON THE POLYMORPHISM OF CYP2C9 GENE

Aim. To assess the efficiency of combined antihypertensive therapy in patients with arterial hypertension and obesity depending on the polymorphism of CYP2C9 gene. Materials and methods. Patients with uncontrolled arterial hypertension (1-2 stage) and obesity were included in our study. They were randomized by the method of converts into two groups: the first group (n=70) took the fixed-dose combinations of the valsartan and amlodipine and the second group took the fixed-dose combinations of the perindopril and amlodipine. Blood pressure of all patients was measured according to the recommendation for diagnosis and treatment of arterial hypertension (ESH/ESC, 2013) before and after 8 weeks of the initial treatment. All tested people had venous blood sampling succeeded by DNA extraction and amplification in real time mode polymorphic variants CYP2C9 gene. The improvement of health self-esteem by QALY was determined like increase of index from initial by 10 % and more. Results. It is shown that people with heterozygosis polymorphisms *1/*2 and *1/*3 reached the target level of arterial blood pressure after 8 weeks of combined therapy of valsartan and the amlodipine (93,1% against 57,1% respectively). In addition to the above, the frequency of reaching the target level of the arterial blood pressure in the group of tested people who get angiotensin II receptor blocker and calcium-channel blocker was for certain higher among the patients with polymorphisms *1/*2 and *1/*3 in comparison with the polymorphic variants CYP2C9 gene (91,3% against 57,1% respectively). The improvement of the health self-esteem by QALY of the tested patients with polymorphisms *1/*2 and *1/*3 CYP2C9 gene is seen more often between the patients of the first group than between patients of the second group (95,6% against 66,7% respectively). Conclusion. Determined interrelation between the efficiency level of the combined antihypertensive therapy with the CYP2C9 gene polymorphism can be considered in cases of insufficient effect of assigned therapy or the uncontrolled character of the arterial hypertension. In our opinion, appropriate personalized correction of therapy will contribute to its optimization relating to the patients with arterial hypertension and obesity.

INTERRELATION OF ANTIHYPERTENSIVE EFFECT OF COMBINATION OF VALSARTAN AND AMLODIPINE WITH VARIOUS POLYMORPHIC VARIANTS OF GENES CYP2C9 AND CYP11B2 IN PATIENTS WITH OBESITY

Aim. To assess the efficiency of combined antihypertensive therapy in patients with arterial hypertension and obesity depending on the polymorphism of CYP2C9 andCYP11B2 genes. Materials and methods. 80 patients with obesity and concomitant uncontrolled medicamentally arterial hypertension (1-2 stage) were included in our study. These patients took the fixed dose combination of the valsartan and amlodipine in a dose of 80-160/5-10mg per day. Blood pressure of all patients was measured by the procedure mentioned in the recommendations for diagnosis and treatment of arterial hypertension (ESH/ESC, 2013; РМОАГ, 2010) before and after 8 weeks of treatment. All tested people had venous blood sampling succeeded by DNA extraction from leukocytes. The amplification of the polymorphic variants CYP2C9 andCYP11B2 genes was performed in real time by means of primers and probes (Synthol, Russia) and Taq Man method (allele discrimination). Results. It is shown that the patients with *1/*2 variant of CYP2C9 gen reached the target level of the arterial blood pressure more often than patients who had polymorphism *1/*1 (92,8% against 47,3%) while analyzing the efficiency of the treatment with account of the polymorphic variants of CYP11B2 gene the reaching of the target level of the arterial blood pressure was seeing more often in the case of mutant polymorphism *2/*2 then in the case of *1/*2 polymorphism (76,5% against 50%). It was also determined that the accurate predominate of *2*2 polymorphism CYP11B2 gene over other its variants was seeing among the patients with more frequent polymorphism of CYP2C9 − *1/*1 who reached the target level of the arterial blood pressure after 8 weeks of the therapy. Conclusion. The interrelation between the antihypertensive combination of valsartan and amlodipine with the polymorphism of CYP2C9 and CYP11B2 genes witch was determined in our study can be considered in cases of the treatment of the patients who suffer from arterial hypertension and obesity. Probably, new usage of the genetic testing results as one of the individualized medicine direction may promote the optimization and effectiveness of the combined medical treatment among the patients with arterial hypertension and obesity.

Optimization combination antihypertensive therapy in patients with hypertension depending on indicators daily monitoring of blood pressure

Optimization combination antihypertensive therapy in patients with hypertension depending on indicators daily monitoring of blood pressure

Combined Antihypertensive Therapy in Patients at High Risk

Presents opportunities to increase the effectiveness of combination antihypertensive therapy (AHT) in patients with arterial hypertension (AH) and high cardiovascular risk. Displaying increase in the proportion of patients with target blood pressure up to 82.4%; high commitment combined AHT (96%) and medical recommendations for lifestyle changes (54%) using the power of information computer technology (ICT) in order to carry out continuous monitoring of blood pressure and other risk factors (RF), commitment to the patients drug and non-drug assignments. Thus, ICT can be seen as a tool that can give a real idea of the scale and nature of the deviation from the medical recommendations that can serve as a basis for personalized AHT.

Преимущества фиксированной комбинированной антигипертензивной терапии у больных с цереброваскулярной патологией: фокус на комбинации «бисопролол + амлодипин»

Преимущества фиксированной комбинированной антигипертензивной терапии у больных с цереброваскулярной патологией: фокус на комбинации «бисопролол + амлодипин»

Algorithm for differential administration of combination antihypertensive therapy in patients with Type 2 diabetes mellitus

Aim. To compare the effectiveness of three variants of long-term combination antihypertensive therapy (AHT), based on two methods of renin-angiotensinaldosterone system (RAAS) inhibition (angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARAII)) or on calcium channel blockade with a dihydropyridine calcium channel blocker (CCB), all of which were administered in order to achieve target levels of blood pressure (BP). To develop an algorithm for differential administration of combination AHT in patients with arterial hypertension (AH) and Type 2 diabetes mellitus (DM-2). Material and methods. The study included 71 patients (mean age 56,8±6,5 years) with AH and DM-2, but without clinically manifested nephroangopathy. The therapy course (30–32 weeks) was completed by 69 patients. All participants were randomised into three groups. The ACEI+CCB group (n=22) received perindopril (5–10 mg/d), indapamide SR (1,5 mg/d), and amlodipine (5–10 mg). The ARAII+CCB group (n=25) was administered valsartan (80–160 mg/d), indapamide SR, and amlodipine. The CCB+BAB group (n=22) received amlodipine (5–10 mg/d), indapamide SR, and metoprolol succinate (50–100 mg/d). The doses of AHT were increased stepwise. At baseline and after 30–32 weeks of the treatment, 24-hour BP monitoring (BPM), renal artery ultrasound and Doppler ultrasound, carbohydrate and lipid metabolism assessment, and 24-hour albumin excretion measurement were performed. Results. Target BP levels were achieved in the majority of patients from all three groups. For the two-component combination AHT, target BP levels were achieved more often with the combination of RAAS inhibitors and indapamide SR, compared to the combination of CCB and indapamide SR. Most patients receiving the latter combination required additional administration of a third medication, in order to achieve adequate BP control. The combination of CCB and BAB increased intrarenal vascular resistance and less effectively controlled night-time systolic AH, compared to the combination of RAAS inhibitors and CCB. The combination of ACEI and CCB, compared to the ARAII+CCB combination, was associated with improved glycemic control, effective reduction of the duration of night-time diastolic AH and night-time heart rate, and normalisation of initially elevated intrarenal vascular resistance at the level of segmental intrarenal arteries. These findings were used for the development of the algorithm for differential administration of combination AHT in patients with AH and DM-2. Conclusion. In DM-2 patients, long-term combination AHR with ACEI and CCB demonstrates more beneficial effects on the metabolic and neurohumoral regulation processes, compared to the combination of ARAII and CCB. These benefits are particularly pronounced in patients with inadequate glycemic control and increased intrarenal vascular resistance. The combination of CCB and BAB inadequately controls night-time systolic AH and does not improve renal hemodynamics.

Combination antihypertensive therapy in patients with arterial hypertension and coronary heart disease

The leading positions in the treatment of patients with arterial hypertension (AH) and coronary heart disease (CHD) are held by angiotensin-converting enzyme (ACE) inhibitors and beta-adrenoblockers (BAB), which have demonstrated their effectiveness in terms of improved patients’ survival. In patients with AH and CHD, the rational, pathogenetic pharmacotherapy using a combination of an ACE inhibitor zofenopril and a highly cardio-selective and vasodilating BAB nebivolol demonstrates antihypertensive and antiischemic action, decreases the risk of potential adverse cardio-metabolic effects, reduces the severity of endothelial dysfunction, and, consequently, improves quality of life.

Moxonidine-based combination antihypertensive therapy in patients with metabolic syndrome

Aim.To assess the effects of moxonidine-based combination therapy on clinical status, laboratory parameters, and target organs in patients with metabolic syndrome (MS).Material and methods.In total, 60 MS patients with Stage 1-2 arterial hypertension (AH) were randomised into 3 groups. Group I was administered moxonidine (0,2-0,4 mg/d) and amlodipine (5-10 mg/d); Group II received moxonidine (0,2-0,4 mg/d) and hydrochlorothiazide (12,5 mg/d); Group III was treated with moxonidine (0,2-0,4 mg/d) and enalapril (10-20 mg/d). At baseline and after 24 weeks of treatment, the following characteristics were assessed: waist circumference (WC), body mass index (BMI), 24-hour blood pressure monitoring (BMP) parameters, left ventricular myocardial mass index (LVMMI), E/A ratio, isovolumetric relaxation time (IVRT), deceleration time (DT) of early diastolic velocity, peak Em velocity at interventricular septum and lateral wall levels, E/Em ratio (myocardial tissue Doppler echocardiography), pulse wave velocity (PWV) between descending aorta and aortic bifurcation levels (ultrasound method), and stiffness index β of ascending aorta. In addition, lipid, carbohydrate, and purine metabolism parameters were assessed; glomerular filtration rate (GFR) was calculated (MDRD method); and urine albumin levels were measured.Results.In Group I (moxonidine + amlodipine), target blood pressure (BP) levels were achieved in 70% of the patients. Systolic BP (SBP) levels, LVMMI, and DT decreased by 19,3±11,4 mm Hg, 4,4 g/m2 (p=0,09), and 10,6 ms (p&lt;0,05), respectively. The increase in E/A ratio and Em annular velocity (Em av) reached 0,4 (p&lt;0,05) and 1,4 cm/s (p&lt;0,05), respectively, while E/Em av ratio decreased by 0,8 (p&lt;0,05), and PWV decreased by 1,6 ms (p&lt;0,05). The BMI decrease reached 0,7 kg/m2 (p&lt;0,05). In Group II (moxonidine + hydrochlorothiazide), target BP levels were achieved in 40% of the participants, with a decrease in SBP levels by 14,7 mm Hg (p&lt;0,05). DT was reduced by 9,4 ms (p&lt;0,05), E/A ratio increased by 0,1 (p&lt;0,05), while PWV, BMI, and GFR decreased by 1,3 m/s (p&lt;0,05), 0,8 kg/m2 (p&lt;0,05), and 5,6 ml/min/1,73 m2 (p&lt;0,05), respectively. In Group III (moxonidine + enalapril), 60% of the patients achieved target BP levels, and SBP levels were reduced by 21,1 mm Hg (p&lt;0,05). LVMMI decreased by 5,1 g/m2 (p&lt;0,05), Em av increased by 0,3 cm/s (p&lt;0,05), while the respective reduction in PWV, WC, and BMI reached 1,1 m/s (p&lt;0,05), 1,8 cm (p&lt;0,05), and 0,5 kg/m2 (p&lt;0,05). All three groups demonstrated a significant reduction in urine albumin levels.Conclusion.The moxonidine-based combination therapy effectively reduced the levels of BP and urine albumin. The combination of moxonidine with amlodipine or enalapril improved cardiac structure and function, as well as renal excretory function. The combination of moxonidine and hydrochlorothiazide, however, negatively affected renal excretion. All three variants of combination therapy were metabolically neutral and demonstrated beneficial effects on visceral obesity.