Combination Antihypertensive Therapy Research Articles

Age and gender disparities in the prevalence of lipitension

Abstract Introduction Lipitension is the presence of hypertension and dyslipidaemia in one person. It multiplies cardiovascular risk up to three-fold and therefore requires timely diagnosing and treatment. Purpose In the present study, we calculated the prevalence of lipitension and its disparities depending on gender and age. Methods We used the randomized sample of the ESSE-RF study that included 1603 urban and rural Krasnoyarsk Krai inhabitants aged 25–64. Each study participant signed informed consent and underwent the questionnaire, office blood pressure measurement, anthropometry, and biochemical blood analysis. Hypertension criteria were the measured systolic blood pressure at 140 mm Hg or higher, the measured diastolic blood pressure at 90 mm Hg or higher, or antihypertensive medications intake. Dyslipidaemia criteria were the total cholesterol level higher than 5.0 mmol/l, the low-density lipoprotein level higher than 3.0 mmol/l, the high-density lipoprotein level lower than 1.0 mmol/l in males and 1.2 mmol/l in females, or triglycerides level higher than 1.7 mmol/l. Results In 40.0% of people, we found a combination of at least one hypertension criterion and at least one dyslipidaemia criterion. The prevalence of lipitension significantly (chi-square for trend; p<0.001) increased from 10.7% in the 25–34 age group to 66.6% in the 55–64 age group. At a younger age, males had dyslipidaemia more frequently than females, while at 55–64, the prevalence of lipitension was higher in females. The details of age and gender disparities are shown in Table 1. Conclusion At least 40% of the general population and two-thirds of people older than 55 have lipitension and need a combined antihypertensive and lipid-lowering therapy. Funding Acknowledgement Type of funding sources: None. Table 1

Initial combination therapy for hypertension in patients of African ancestry: a systematic review and meta-analysis

Abstract Background Initial antihypertensive combination therapy is considered the standard of care in most patients with hypertension. However, while monotherapy with calcium channel blockers (CAB) or Diuretics is known to have greater blood pressure lowering efficacy than other drugs in African ancestry (AA) patients, it is unclear which initial combination therapy is most effective. Therefore, we systematically reviewed the existing evidence on different initial dual combination therapies in these patients. Methods We searched for published and unpublished randomized controlled trials (RCTs) in AA adults with uncomplicated, primary hypertension, which compared two or more initial dual combination drug therapies, and reported blood pressure, morbidity, or mortality outcomes. Searches were conducted without language restriction in electronic databases including PubMed, Embase, CENTRAL, preprint servers, and clinical trial registers, from their inception through March 31, 2021. In addition, we conducted hand search, and contacted authors and pharmaceutical companies for missing information. Trial quality was assessed using the Jadad score. Results We retrieved 1728 reports yielding 10 RCTs (Jadad score 1 to 4, median 3) conducted on 4 continents. Trials' treatment duration was 4 to 156 (median 10) weeks, using combinations of 6 classes of drugs in 23 treatment arms, and providing data on blood pressure (n=10 trials) and morbidity/mortality (n=1 trial) in 3715 patients (34.2% men) aged 18 to 79 years. Initial combination therapy with Diuretics+CAB (vs Diuretics+ACE-inhibitors (ACEI) or Angiotensin II type 1 receptor antagonists (ARB); 4 comparisons) resulted in comparable systolic (SBP) (n=467; −0.10 [−0.23 to −0.03] mm Hg), and diastolic blood pressure (DBP) (n=408; −0.03 [−0.19 to 0.12]). Adverse effects included more hypokalaemia and hyperglycaemia with Diuretics+CAB than Diuretic+ACEI/ARB. No morbidity or mortality outcomes were available. Initial combination therapy with CAB+ACEI/ARB (vs Diuretics+ACEI/ARB; 7 comparisons) also resulted in comparable blood pressures (n=2266; SBP: −0.49 [95% CI, −0.87 to −0.12] and DBP −0.55 [−0.97 to −0.14]); but CAB+ACEI/ARB showed less adverse effects (hypokalaemia, hyperglycaemia), and a trend toward reduced cardiovascular disease and mortality (n=1414; mean follow up 3 y; Amlodipine/Benazepril vs HCT/Benazepril, combined cardiovascular disease and mortality (6.6 vs 8.9%, P=0.10), without significant differences in Stroke (2.2 vs 2.1%, P=0.97), or heart failure (1.7 vs 2.2%, P=0.50). Conclusion In relatively young AA patients with uncomplicated hypertension, initial dual combination therapy including CAB, Diuretics, or Diuretics+CAB results in comparable blood pressures, but adverse metabolic effects are lower without a diuretic. Knowledge gaps include data on biomarkers to replace race/ancestry, data by sex and in the elderly, and end point data, including on Diuretic/CAB and CAB/ARB combinations. Funding Acknowledgement Type of funding sources: None.

Study the features of the course of uncontrolled arterial hypertension in Aral Sea region

Abstract Aral Sea disappearance is a well-known ecological disaster. An arid, sharply continental climate, high mineralization, pollution and a shortage of drinking water in Aral Sea region harm human health. The aim of this work was to study the features of the course of uncontrolled arterial hypertension (AH) in this ecologically unfavorable region. Material and research methods. Surveyed 132 patients hospitalized in the Aral branch of the republican emergency center with hypertensive crisis, uncomplicated form. The average age of patients was 57.2±11.6 years, and 80 (60.6%) were women and 52 were men (39.4%). The duration of hypertension was 8.85±3.4 years. Before study, 41 (31%) patients did not take antihypertensive drugs, 79 (59%) patients were on monotherapy (62% RAAS-blockers, 19% beta-blockers, 19% calcium antagonists) and 10 (7.5%) patients took double combined AGT. Only two patients were on triple combined AGT: RAAS blocker+AK+BAB. Patients characterized by a high cardiovascular risk, on 40 patients diagnosed CHD, 11 patients were suffered myocardial infarction, the consequences of stroke in 8 patients. All patients underwent office measurement of blood pressure, ultrasound of the brachiocephalic arteries, echocardiography, biochemical blood tests, and albumin urinary excretion. The Henken test was performed to determine the salt taste sensitivity. The low threshold of salt taste sensitivity corresponded to the concentration of NaCl less than 0.16%, an average is 0.16%, and high is more than 0.32%. Results Before treatment, SPB was 200.8±22.6 mm Hg, DPB 105.4±7.62 mm Hg, heart rate 79.86±11.54 beats/min. The body mass index (BMI) was 30.2±4.78 kg/m2. All patients have left ventricular hypertrophy (LVH), the indexed mass of the LV myocardium was 171.62±30.9 g/m2. Intima-media thickness of the common carotid artery was 1.24±0.16 mm. Albumin urinary excretion (AUE) averaged 221.0±130.2 mg/day, while norm albuminuria were detected in four patients (3%), microalbuminuria (MAU) in 89 patients (67.4%), and proteinuria in 39 patients (29.6%). Hanken's test showed the presence of a high threshold for taste sensitivity in almost all patients, amounting to 0.51±0.17% NaCl concentration. Conclusion Patients with uncontrolled hypertension and uncomplicated hypertensive crisis living in the Aral Sea region are characterized by low adherence to treatment, the presence of target organ damage, a high threshold for taste sensitivity to table salt, and the severity of daily urinary albumin excretion, in 67.4% of cases with MAU and 29.6% cases of proteinuria. These findings characterize the presence of nephrosclerosis in patients with uncontrolled hypertension. Our results once again point the necessity to early detection of hypertensive patients and the appointment of combined antihypertensive therapy on the part of primary care. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): other

Evidence born from ASCOT trial – still important after 15 years

The paper presents the overview evolution of hypertension identification and treatment during last 15 years after publication of ASCOT trial (AngloScandinavian Cardiac Outcomes Trial) results. It discusses possible mechanism of more significant cardiovascular risk reduction in amlodipine/ perindopril group comparing with atenolol/diuretic group: central blood pressure, arterial stiffness, asleep blood pressure and BP variability. Innovative approaches in time of ASCOТ trial such as combined antihypertensive therapy from start and RAAS inhibitor as first line now became routine practice in actual guidelines. Importance of early prescribing of fixed antihypertensive combination and choice of safe drugs help to improve adherence and decrease resistant hypertension prevalence. Prevention of new onset of diabetes in metabolic patients needs application of metabolically neutral drugs and including of renin-angiotensin-aldosterone inhibitors in combination therapy. Results of ASCOT-Legacy trial demonstrated long-term protective effect of amlodipine/perindopril combination resulting in decreasing mortality, rate of stroke and coronary events during 20-years follow-up.

Оценка сочетанного применения холекальциферола и антигипертензивной терапии у лиц с артериальной гипертензией

Актуальность.Целью исследования стала оценка влияния применения холекальциферола в дозе 2000 МЕ в сутки на уровень 25(ОН)D в сыворотке и артериальное давление на фоне антигипертензивной терапии у больных с артериальной гипертензией II стадии. Материалы и методы. Мы провели проспективное одноцентровое исследование у 115 больных со II стадией АГ (91 женщина и 24 мужчины), средний возраст 50,7 ± 7,1 года. Продолжительность периода наблюдения составила в среднем 15,8 ± 1,8 мес. (от 12 до 18 мес.). Пациенты получали антигипертензивную терапию в соответствии с европейскими рекомендациями: ингибиторы ангиотензинпревращающего фермента или антагонисты рецепторов ангиотензина — лозартан, или диуретики (гидрохлортиазид или индапамид) в составе комбинированной терапии, или антагонисты кальция — амлодипин, или бета-адреноблокаторы, или их сочетание. Каждому второму пациенту было рекомендовано принимать витамин D в виде холекальциферола в дозе 2000 МЕ/день ежедневно. Всем пациентам проводили общий анализ крови, общий анализ мочи, определение сахара в крови натощак, мочевины в сыворотке крови, креатинина в сыворотке крови, систолического и диастолического артериального давления, антропометрических данных, электрокардиографию. Уровень общего витамина D в сыворотке крови определяли с помощью иммуноферментного анализа. Статистический анализ выполняли, используя программный пакет «STATISTICA 10.0» (SN AXAR207F394425FA-Q). Результаты. Было выявлено, что прием диуретиков (гидрохлортиазида в дозе 12,5–25 мг или индапамида в дозе 1,5 мг) в составе комбинированной антигипертензивной терапии оказывает влияние на изменения 25(ОН)D в сыворотке (F = 5,35; p = 0,02) и его уровень (F = 11,8; p = 0,0009). Изменения систолического артериального давления были более выражены (–27,4 ± 17,9) в группе пациентов, получавших диуретик и холекальциферол, по сравнению с группой сравнения, что соответствовало уровню достоверности p < 0,001. В той же группе была выявлена взаимосвязь между динамикой систолического артериального давления и длительностью приема холекальциферола (R = 0,42; p = 0,023). Было обнаружено достоверное влияние как холекальциферола (F = 4,1; p = 0,046), так и диуретиков (F = 14,3; p = 0,0003). Выводы. Тиазидные или тиазидоподобные диуретики оказывают отрицательное влияние на уровень 25(OH)D в сыворотке. Сочетанное применение холекальциферола и диуретика в дозе 2000 МЕ в сутки для лечения пациентов с АГ II стадии позволяет достичь наибольшего антигипертензивного эффекта в отношении систолического артериального давления без риска избыточной концентрации витамина D в организме.

Abstract P108: Side Effects Of Initial Combination Versus Monotherapy For Patients With Hypertension

Clinical guidelines recommend initiating combination antihypertensive therapy for many patients with hypertension. However, data on the risk of side effects are limited. We evaluated side effects associated with initiating combination therapy versus monotherapy among patients with hypertension from Kaiser Permanente Southern California between 2008-2014. Patient characteristics, antihypertensive medication use, and possible side effects were collected using electronic health records. We examined the association of initial combination therapy and incidence of side effects including acute kidney injury, hypotension, injurious fall, hyperkalemia, hypokalemia, hyponatremia, or hyperuricemia using multivariable Cox Proportional hazards models. Of 164,805 patients, 44% initiated combination therapy (34% angiotensin converting enzyme inhibitor (ACEI)-thiazide diuretics (TD); 10% other combinations) and 56% initiated monotherapy (22% ACEIs; 16% TD; 11% beta blockers (BB); 7% calcium channel blockers). Incidence rates of side effects were between 3.8 for hyperkalemia to 55.5 for hypokalemia per 1000 person-yrs during median follow-up of 0.27-0.45 yrs. Initiation of ACEI-TD combination therapy was associated with a lower risk of hyperkalemia than ACEI monotherapy and a lower risk of hypokalemia than TD monotherapy ( Table ). Initiation of ACEI-TD combination therapy was associated with a higher risk of hyponatremia, hyperuricemia, and hypotension, but not associated with injurious falls when compared with other monotherapy groups. Monitoring for side effects following initiation of antihypertensive medication with combination therapy may be useful.

Characterizing Dual Combination Therapy Use in Treatment Escalation of Hypertension: Real-World Evidence from Multinational Cohorts

Background: Over one billion adults have hypertension globally, of whom 70% cannot achieve hypertension control goal with monotherapy alone. Data are lacking on patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Methods: Using eleven electronic health record databases that 118 million patients across eight countries/regions, we characterized the initiation of antihypertensive dual combination therapies for patients with hypertension. In each database, we first constructed cohorts of patients who newly initiate dual combination therapy of the four most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEi] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; beta-blocker; and thiazide diuretic) after escalating from monotherapy, and then described treatment utilization using these cohorts. Findings: We identified 980,648 patients with hypertension who newly initiated dual combination therapy: 12,541 from Australia, 6,980 from South Korea, 2,096 from Singapore, 7,008 from China, 16,663 from Taiwan, 103,994 from France, 76,082 from Italy, and 754,137 from the United States (US). Significant variations in treatment utilization existed across databases and patient subgroups. In Australia and Singapore databases, starting an ACEi/ARB monotherapy followed by a CCB was most common while in South Korea, China and Taiwan databases, starting a CCB monotherapy followed by an ACEi/ARB was most common. In Italy, France, and US databases, sequential use of an ACEi/ARB monotherapy followed by a diuretic was most common. Younger patients were more likely to be prescribed ACEi/ARB then a CCB or a diuretic compared with older patients. Women were more likely to be prescribed diuretics then an ACEi/ARB or a CCB compared with men. Interpretation: Large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic groups. These results highlight the need for future research to identify which dual combination therapy is most effective in practice. Funding: This study was supported by the National Research Foundation Singapore under its AI Singapore Programme (Award Number: AISG-GC-2019-002), National Medical Research Council (NMRC) under the Open Fund - Large Collaborative Grant (OF-LCG) - NMRC/OFLCG/001/2017 and Center Grant (CG) schemes - NMRC/CG/C016/2017, the Bio Industrial Strategic Technology Development Program (20003883, 20005021), the Ministry of Trade, Industry & Energy (MOTIE, Korea), a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the Ministry of Health &Welfare, Republic of Korea (grant number: HR16C0001), the Australian Government National Health and Medical Research Council (NHMRC Grant Number: APP1192469). Declaration of Interest: JL, XW, CR MVZ are employees of IQVIA. YL reports grants from the National Heart, Lung, and Blood Institute (K12HL138037) and the Yale Center for Implementation Science. She was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion. HMK received expenses and/or personal fees from UnitedHealth, IBM Watson Health, Element Science, Aetna, Facebook, the Siegfried and Jensen Law Firm, Arnold and Porter Law Firm, Martin/Baughman Law Firm, F-Prime, and the National Center for Cardiovascular Diseases in Beijing. He was a co-founder of Refactor Health and HugoHealth and had grants and/or contracts from the Centers for Medicare & Medicaid Services, Medtronic, the U.S. Food and Drug Administration, Johnson & Johnson, and the Shenzhen Center for Health Information. MAS reports grants from US National Science Foundation, grants from US National Institutes of Health, grants from the US Department of Veterans Affairs, grants from IQVIA, and personal fees from Janssen Research & Development and Private Health Management. SCY reports grants from Korean Ministry of Health & Welfare, grants from Korean Ministry of Trade, Industry & Energy. RWP reports grants from Korean Ministry of Health & Welfare, grants from Korean Ministry of Trade, Industry & Energy. The other co-authors report no potential competing interests. Ethical Approval: Use of TMUCRD data has been approved by theTMU-Joint Institutional Review Board (Project number: TMU-JIRB N202011003).

Effect of combination antihypertensive therapy, including renin-angiotensin-aldosterone system inhibitors, on oxidative stress and arterial remodeling in hypertensive patients with heart failure with preserved ejection fraction

Aim. To study the effect of triple combination therapy on oxidative stress and arterial remodeling in hypertensive patients with heart failure with preserved ejection fraction (HFpEF).Material and methods. The study involved 76 people with diagnosed HFpEF. After a comprehensive examination, patients were randomized into two equal groups: first group — patients who received perindopril 10 mg, indapamide 2,5mg and amlodipine 5 mg; second — patients who received losartan 100 mg, indapamide 2,5 mg, amlodipine 5 mg. Before and 16 weeks after the therapy initiation, cardiac ultrasound, assessment of endothelial function with estimating endothelium-dependent vasodilation, assessment of vascular stiffness by photoplethysmography and compression oscillometry were carried out. The plasma concentration of oxidative stress marker 8-isoprostane was studied.Results. During the follow-up period, a significant improvement in endothelial function was noted: in the first group — from 8,1% to 11,4% (p=0,001), in the second — from 5,8% to 8,3% (p=0,0007). In both groups, there was an improvement in microvessel elasticity: a significant decrease in specific peripheral vascular resistance, as well as a significant decrease in total peripheral resistance in the first group (p<0,002) and a tendency to decrease in the second one (p>0,05). There was a significant increase in the stiffness of the aorta and muscular arteries in both groupsю In the first group, a stiffness index decreased from 10,38 m/s to 8,33 m/s (p<0,0001), in the second — from 10,6 m/s to 9,3 m/s (p<0,01). In addition, resistance index in the first group decreased from 71,5% to 60% (p<0,0001), while in the second — from 68% to 60% (p=0,006). Also, both groups showed a significant decrease in the left atrial diastolic dimension and the left atrial volume index. A decrease in the 8-isoprostane plasma levels was noted, which indicates a decrease in oxidative stress.Conclusion. Oxidative stress, which develops due to chronic systemic inflammation, plays a key role in the pathogenesis of HFpEF. The results obtained show an improved endothelial function as a result of decrease in oxidative stress, which is accompanied by an improvement in vessel wall elasticity, thereby slowing down the heart failure progression.

Adipokines in patients with hypertensive disease with obesity in the dynamics of combined antihypertensive therapy

Hypertensive disease today is one of the most common cardiovascular diseases, as well as the most common disease associated with obesity. Evaluation of the level of adipokines, namely adiponutrin and galanin, depending on the degree and duration of hypertension, the degree of obesity and their correction against the background of combined antihypertensive therapy is relevant for further understanding of this comorbidity and improvement of the early diagnostics. 127 people were examined, including 107 patients with hypertension of degree 1–3 and 20 healthy persons. Of the patients included in the study, the adiponutrin and the galanin levels were determined in 58 patients, out of which 22 were prescribed different regimens of combined antihypertensive therapy. To determine the level of adiponutrin and galanin, an enzyme-linked immunosorbent assay was used. A significant increase was found in the blood serum of the examined adipokines in comparison with the control group: the galanin level was 4.8 times higher than in the control group, the adiponutrin level in patients with this comorbid pathology was 3.3 times higher than that in the control group. The galanin level is most pronounced in patients with hypertension of degree 3 and obesity of degree 3, which is confirmed by the presence of a direct correlation with systolic, diastolic and pulse blood pressure, very low density lipoprotein cholesterol. The adiponutrin level in the blood serum increased correspondingly to the increase in body mass index: in patients with obesity of degree 3 it was 15.8 times higher than this indicator in patients with normal body weight, 8.8 times higher than in patients with overweight, 6.1 times higher than in patients with obesity of degree 1 and 2.5 times higher than in patients with obesity of degree 2. The levels of the studied adipokines in patients differed also relative to the duration of hypertension. There was a 1.8-, 5.1-, 5.2-fold increase (respectively, ≤5, 6–10, >10 years) of the galanin content in the blood serum compared to the control group. Also an increase of the serum adiponutrin level was noted in comparison with the control group. Against the background of combined antihypertensive therapy, we observed favourable dynamics of galanin and adiponutrin. It is important to conduct further studies to assess the activity of galanin and adiponutrin with a longer follow-up period in wider populations.

THE APPLICATION OF COMBINED PREPARATIONS WITH CONSTANT DOSES OF ANTIHYPERTENSIVE DRUGS AS THE INITIAL TACTICS OF TREATMENT AT HIGH BLOOD PRESSURE LEVEL: PROVEN FACTS AND EXPERT’S OPINION

In this article the current problems of the use of combined antihypertensive drugs in the implementation of «tactics one tablet» in a wide range of patients with arterial hypertension are discussed. The results of the discussion of such a problem by experts, as well as the main provisions of the agreement document, are given, devoted to approaches to the implementation of tactics of wider use of combined antihypertensive drugs containing 2 or more antihypertensive drugs in one tablet. Both the advantages and disadvantages of «tactics one tablet « are considered. The results of clinical studies are discussed, which confirm the validity of the use of the combined antihypertensive therapy as an initial tactic of treatment of the majority of patients with arterial hypertension. The results of the assessment of pharmacoeconomic indicators are given when using combined antihypertensive therapy.

Adherence to Treatment by Initial Antihypertensive Mono and Combination Therapies.

Aim of our study was to compare adherence to antihypertensive drug therapy between newly treated patients in whom monotherapy or a 2-drug single-pill combination (SPC) was initially dispensed. The 63,448 residents of Lombardy Region (Italy), aged 40-80 years, who were newly treated with antihypertensive drugs during 2016, were identified and followed for 1 year after the first prescription. The outcome of interest was adherence to drug therapy that was measured according to the "proportion of days covered" (PDC) criterion, i.e., the ratio between the number of days in which the drug was available and the days of follow-up. Patients who had a PDC >75% and <25% were defined as highly and poorly adherent to drug therapy, respectively. Log-binomial regression models were fitted to compare the propensity to treatment adherence between the initial therapeutic strategies, after adjusting for baseline demographic and clinical covariates. About 46% and 17% of patients showed high and poor adherence, respectively. Compared with patients under initial monotherapy (85%), those who were initially treated with a SPC (15%) had higher propensity to be highly adherent and a lower propensity to be poorly adherent to antihypertensive treatment (risk ratio: 1.18, 95% confidence interval 1.16-1.21; 0.42, 0.39-0.45, respectively). This was the case regardless the sex, the age, the patient clinical status, and with almost any type of SPC. In a real-life setting, patients who were initially prescribed a 2-drug SPC exhibited more frequently a good adherence to antihypertensive treatment than those starting with a single drug.

Effectiveness and Tolerability of the Single-Pill Combination of Bisoprolol and Perindopril in Patients with Arterial Hypertension and Stable Coronary Artery Disease in Daily Clinical Practice: The STYLE Study.

IntroductionCombination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and tolerability of bisoprolol/perindopril (Bis/Per) single-pill combination (SPC) in Russian patients with hypertension and coronary artery disease (CAD) treated in routine clinical practice.MethodsSTYLE (NCT03730116) was an open-label, uncontrolled, prospective observational study conducted in patients who were already receiving Bis/Per SPC, switched to SPC from Bis or Per monotherapy, or switched from a free combination of Bis and Per. Primary endpoint criteria were assessed at 1 and 3 months and included change in mean office systolic/diastolic blood pressure (SBP/DBP), proportion achieving target BP (< 140/90 mmHg), and measures of antianginal effectiveness.ResultsThe full analysis set comprised 1892 subjects. Mean age was 61.9 ± 8.8 years, 53.2% were women, and mean durations of hypertension and CAD were 12.5 ± 7.9 and 7.2 ± 6.4 years, respectively. Mean SBP/DBP decreased by 22.3/11.0 mmHg and 31.5/15.9 mmHg at 1 and 3 months, respectively (P < 0.0001 vs baseline). Target BP was achieved by 49.2% and 86.7% of patients at 1 and 3 months, respectively. Reductions in mean number of angina attacks and nitrate consumption and improvements in heart rate were statistically significant. Treatment was well tolerated.ConclusionTreatment of patients with hypertension and CAD with Bis/Per SPC for 3 months was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by an improvement in angina symptoms. Treatment was well tolerated in a broad patient population representative of those seen in everyday clinical practice.Infographic

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.

A clinical case of refractory arterial hypertension

Arterial hypertension is considered treatment refractory (resistant), if the treatment, involving a change (improvement) in lifestyle and a rational combined antihypertensive therapy, consisting of three drugs, including a diuretic, in the maximum tolerated doses does not lead to the achievement of the target blood pressure level. Pseudo-refractory and true refractory arterial hypertension are distinguished. According to modern data, true refractory arterial hypertension occurs in no more than 5 % of cases among the entire population of patients with arterial hypertension, however, in certain groups of patients, for instance, with chronic kidney disease, its prevalence can reach 30–50 %. The article presents a clinical case of diagnosis and treatment of refractory arterial hypertension.

Evolution of antihypertensive combined therapy: from depressin of academician A. L. Myasnikov to modern multi-component drugs

The article shows the historical background to the emergence and subsequent development of combined antihypertensive therapy from creation of a multi-component drug to modern fixed combinations as the most effective approach in the treatment of hypertension (HTN). The authors consider that Russian scientist therapist academician of the USSR Academy of medical Sciences A. L. Myasnikov, has priority in the development of fixed drug combination concept, created depressin powder. The development of pharmacology as a science and the achievements in pharmaceutical technologies contributed to the expansion of possible drugs combination for HTN treatment, and the discovery of new diverse pathophysiological mechanisms implemented in this pathology led to the understanding of the need for combined drugs in clinical practice. The advantages of combination HTN therapy versus monotherapy include rapid achievement of the target blood pressure level, low frequency of tachyphylaxis, longer-lasting antihypertensive effect, no need to change drugs, higher compliance, effective organoprotection and cardiovascular risk reduction, positive and/or neutral effects on the main parameters of metabolism, reduced frequency and severity of side effects. Taking into account these facts, as well as the wide prevalence of HTN in the population, its high medical and social significance, the key role in atherosclerosis, it is necessary to develop new combined domestic drugs for the treatment of HTN and their inclusion in the list of vital medicines, increasing the availability of these drugs for the population on the basis of preferential programs.

THERAPEUTIC EFFECTS OF MINERAL CORTICOID RECEPTOR BLOCKER IN THE COMBINATION ANTIHYPERTENSIVE DRUG THERAPY IN HYPERTENSIVE PATIENTS

Objective: Among the components of renin-angiotensin-aldosterone system, aldosterone is supposed to facilitate the progression of cardiovascular organ injuries not only by promoting renal tubular Na reabsorption but also by causing oxidative stress, inflammation and cardiovascular tissue hypertrophy and fibrosis. Therefore, mineral corticoid receptor blockers (MRB) are expected to exhibit protective effects against cardiovascular organ injuries in hypertensive patients. In the present study, the therapeutic effects of MRB in the combination antihypertensive treatment were examined in hypertensive patients. Design and method: Fifty mg eplerenone (EPL) was added to 24 hypertensive patients under antihypertensive drug therapy who were not achieved the target blood pressure levels. The combination was continued for 3 to 4 months and the effects on blood pressure (BP) and laboratory data including renal function and cardiovascular endocrine system were evaluated. Results: After 3–4 months, office BP was lowered from 148/91 to 135/86 mmHg (p &lt; 0.001/p = 0.002) as well as the home BP (morning 150/86 to 134/81, p = 0.001/p = 0.033; evening 139/80 to 127/74, p = 0.005/p = 0.030). Serum K (4.2 to 4.3mEq/L, p = 0.014) and creatinine (0.82 to 0.87 mg/dL, P &lt; 0.001) were slightly but significantly increased. Serum uric acid was significantly also increased from 5.8 to 6.4 mg/dL (p = 0.015). However, the indices of glucose metabolism and serum lipids were not affected. In addition to the natural increases in plasma renin and aldosterone, plasma B-type natriuretic peptide (BNP: 23 to 17 pg/mL, p = 0.028) and urinary albumin excretion (111 to 70 mg/gCr, p = 0.009) were significantly decreased. Conclusions: In the combination antihypertensive drug therapy, MRB is expected to cardiac and renal injuries and the influences on glucose and lipid metabolisms seem negligible, however, care should be taken for the development of hyperuricemia and renal dysfunction in addition to hyperkalemia.

ANTIHYPERTENSIVE DRUG THERAPY BETWEEN ELDERLY PATIENTS IN A RURAL AREA OF PORTUGAL

Objective: The aim of this study is to evaluate the antihypertensive therapy among &gt; 65 years old in a rural area of Portugal. Design and method: The study includes 400 patients 65–93 years old. Average age was 76.2 ± 6.8 years old (76.4% women). The 40.3% of individual have complete basic education and 4% still continued to work. Study was conducted in several internal medicine external offices of a Hospital in a rural area of Portugal from October 2017 to May 2019. The presence of High Blood Pressure (HBP), cardiovascular diseases (CVD) and antihypertensive therapy was evaluated in 2 groups of patients: 65–79 years old (n = 336) and &gt; 80 years old (n = 64). Results: Antihypertensive therapy was reported by 93% (n = 372) patients. The 45,46% of the patients (n = 171) received monotherapy. Combination of two-drugs were taken by 31.98% (n = 119) of the patients. Three and four drugs combination were taken by 16,12 % (n = 60) and 5,91% (n = 22) of the patients, respectively. The study revealed ACE inhibitors and like thiazides diuretics as most frequent drugs (52.8% and 49.6% of patients, respectively). The distribution of another groups of antihypertensive pills is following: calcium channel blocker - 39.6%, angiotensin receptor blocker - 24.7%, beta blocker - 14% patients and central action blockers 6,5 %. In patients taking 2 anti-hypertensive drugs, the most frequent association was ACE inhibitors and like thiazides diuretics (42,3 %) followed by ACE inhibitor plus calcium channel blocker (28,5 %). In patients taking 3 drugs, the most frequent association was ACE inhibitor plus like thiazide diuretic plus calcium channel blocker. Conclusions: Most hypertensive patients &gt; 65 years old receive combination antihypertensive therapy. Combinations of ACE inhibitors + like thiazides diuretics or ACE inhibitors + calcium channel blocker are among the most common.

Peculiar features of arterial hypertension state on the background of atherosclerosis (clinical and instrumental comparisons)

A comparative analysis of the clinical and functional state of patients with arterial hypertension (AH), depending on the presence or absence of arterial sclerotic disease of the arterial bed is represented. 2 groups of 110 and 60 patients respectively were formed. The 1st group included persons with arterial hypertension (AH) and atherosclerotic changes in the arterial bed, the 2nd — with hypertension and without any atherosclerotic changes. It is shown that patients with hypertension and stenotic changes of the vascular bed are characterized by an increase in the levels of diastolic blood pressure and indicators of systolic and diastolic pressure load during the day. They have signs of structural changes in the cardiovascular system, as proved by indicators of arterial stiff ness, myocardium remodeling, circadian rhythms of blood pressure abnormalities, and, in addition, kidney damage in a chronic form of disease, stage 2–3.On the contrary, hypertension without atherosclerotic changes of the vascular bed is characterized by higher values of systolic blood pressure, increased variability of systolic and diastolic blood pressure during the day, and, in addition, atherogenic dislipoproteinemia and hyperuricemy within the metabolic syndrome are present. As a clinical sign of atherosclerotic vascular changes in patients with hypertension, more “severe” blood pressure is observed. It requires combined antihypertensive therapy, consisting of 3 or more groups of medications.

Экономическое обоснование затрат на снижение артериального давления при комплексной терапии артериальной гипертензии с приемом холекальциферола

Целью исследования был расчет затрат на снижение артериального давления (АД) при комплексной терапии артериальной гипертензии (АГ) с приемом холекальциферола и без него. Материалы и методы. 154 пациента с АГ II степени были распределены в группу принимавших комбинированную антигипертензивную терапию и холекальциферол 2000 МЕ/сут (АГ(+Х)) и группу сравнения (АГ(–Х)). Измеряли офисное артериальное давление, уровень общего витамина D в крови. Рассчитывались затраты на медикаментозную терапию. Результаты. При повторном обследовании уровень витамина D в крови повысился и в группе АГ(+Х) стал выше (р = 0,0000001), чем в группе АГ(–Х). Стоимость медикаментозной терапии на 1 человека в группе АГ(+Х) была выше, чем в группе АГ(–Х) (106,8 и 91,5 $ соответственно), однако стоимость снижения 1 мм рт. ст. систолического артериального давления (САД) в группе АГ(+Х) была на 3,9 $ меньше, чем в группе АГ(–Х). Прием холекальциферола в дозе 2000 МЕ/сут на протяжении 3 мес. позволяет достичь оптимального уровня витамина D в организме в 83% случаев независимо от антигипертензивной терапии. Прием холекальциферола в дозе 2000 МЕ/сут от 6,5 до 12 мес. позволяет достичь оптимального уровня витамина D в крови в 100% случаев. Наибольшая динамика повышения уровня 25(ОН)D в крови в ответ на прием холекальциферола наблюдается при исходном его уровне &lt; 20 нг/мл. Выводы. Экономические затраты на снижение САД с более частым достижением его целевых значений были наименьшими при комплексной терапии с использованием холекальциферола, особенно в сочетании с диуретиком. Кроме того, при комплексной терапии мы получили коррекцию не только АД, но и статуса витамина D в организме.

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.