Combination Antihypertensive Therapy Research Articles

Prykhylnist do likuvannia ta chynnyky, yaki vplyvaiut na yakist likuvannia arterialnoi hipertenzii u patsiientiv u viddalenyi period pislia perenesenoho infarktu miokarda

Introduction. Adherence to the treatment of arterial hypertension (AH) after myocardial infarction (MI) remains an understudied problem in world cardiology. The aim of the study. Assess adherence to treatment and the factors that affect it in patients with AH in the remote period after MI. Materials and methods. The study included 265 patients after MI (68.2 % of men, mean age 65.4 ± 9.5 years). The mean time from MI to inclusion in the study was 2.3 ± 1.9 years. Assessment of the quality of secondary prevention was performed by analyzing the results of the questionnaire, measuring of anthropometric parameters, blood pressure (BP) and heart rate (HR), as well as determining lipid metabolism, creatinine and venous blood glucose. Results. The frequency of detection of AH in the long period after MI is 69.1 %, regardless of gender, time of MI and its variant and increases in proportion to age. Only in 26.3 % of patients with hypertension in the remote period after MI BP was within the target values. Factors associated with achieving the target values of BP were age up to 60 years (OR – 1.35; p is equal to 0.02), a visit to the doctor during the last 6 months (OR – 1.82; p is equal to 0.002), regular independent blood pressure measurement (OR – 1.63; p is equal to 0.01). 13.3 % of patients with AH after MI did not take antihypertensive drugs, the remaining 60.4 % of patients with AH were treated but did not reach the target BP. Among patients with AH after MI who did not take antihypertensive drugs, patients older than 60 years prevailed (83.3 % vs. 63.2 % of treated patients, p = 0.05). In addition, much less often these patients were under the supervision of a doctor – 47.4 % vs. 82.8 % (p is equal to 0.0005), including a cardiologist (40.9 % vs. 75.0 %, p is equal to 0.001), less visited a doctor for a year, had lower BP, and had poorer knowledge of post-MI treatment. In addition, none of them use statins. Patients with AH who received treatment but did not reach the target BP values received the same amount of antihypertensive drugs as patients with controlled AH – an average of 2.1 ± 1.0 and 2.1 ± 0.9 drugs, respectively. At the same time, 29.3 % of patients in the group of ineffectively treated AH received monotherapy. No differences were found between age, sex, basic clinical and social parameters, financial status, health knowledge, self-measurement of blood pressure, or frequency of physician visits. Conclusions. To achieve the target BP levels in patients with AH after MI, it is necessary to: introduce regular measurement of home BP in all patients; use combination antihypertensive therapy, including, if necessary, with the use of three or more drugs; regularly monitor adherence to treatment, use of antiplatelet, antihypertensive drugs and statins. Patients with difficult-to-control AH should consult a cardiologist at least every 6 months.

Identifying and treating resistant hypertension in PRECISION: A randomized long-term clinical trial with aprocitentan.

The design and baseline data of the PRECISION study, which evaluates the effect of the dual endothelin receptor antagonist aprocitentan on blood pressure (BP) in patients with resistant hypertension (RHT) are presented. The study is a blinded, randomized, parallel‐group Phase 3 study and its three‐part design assesses the short‐term and sustained long‐term effects of aprocitentan on BP. Results are expected in 2022.Patients with uncontrolled BP (measured as unattended automated office BP) despite the use of three or more antihypertensive medications for at least 1 year were screened. They were switched to a single‐tablet triple fixed combination antihypertensive therapy for at least 4 weeks before entering a single‐blind placebo run‐in period. The 4‐week placebo run‐in period further excluded placebo responders. The randomization period consisted of three sequential parts: (1) a 4‐week double‐blind part with aprocitentan 12.5 mg, 25 mg, or placebo (1:1:1 ratio); (2) a 32‐week single‐blind part with aprocitentan 25 mg; and (3) a 12‐week randomized withdrawal part with aprocitentan 25 mg or placebo (1:1 ratio). The purpose was to demonstrate the BP lowering effect of aprocitentan in RHT (Part 1) and the persistence of this effect (Parts 2 and 3).Out of 1965 screened patients, 730 were randomized resulting in an overall inclusion failure rate of 62.8%. The most common reason for exclusion (44.4% of all screened patients) was failure to meet the BP inclusion criteria. These results underline the high proportion of pseudoresistant hypertension among patients referred for RHT.

DINAMICS OF ARTERIAL STIFFNESS USING CAVI INDEX DEPENDS ON ADDED STATIN TO FIXED COMBINATION ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH ARTERIAL HYPERTENSION

Objective: Aim of this study was to evaluate dynamics of arterial stiffness using cardio-vascular index (CAVI), of the fixed triple combination of valsartan / amlodipine / hydrochlorothiazide and a double fixed combination of valsartan / amlodipine in the treatment of patients with arterial hypertension II-III degree depends on added statin therapy. Design and method: The study included patients with moderate and severe arterial hypertension without diabetes. Patients were divided into 2 groups. The first group (n = 59) was assigned a fixed combination of Val/Amlo/HCT of Val/Amlo plus statins. Patients in the second group (n = 40) received fixed combination Val/Amlo/HCT or Val/Amlo without statins. After 6 months of treatment there was control of therapy. Results: The study included 99 patients with moderate and severe hypertension. The average age of patients 1-st group - 58.05 ± 1.28 (37–75) years, 2-d group – 50,05 ± 2.30 (24–76) years. Office SBP/DBP at the beginning 1-st group - 162.25 ± 1.53/97.36 ± 1.20 mm Hg and 160.85 ± 2.18/100.30 ± 1.64 mm Hg in 2-nd group. The office heart rate was 70.07 ± 1.14 bpm and 71.90 ± 1.71 bpm respectively. At baseline, 24-h ambulatory SBP/DBP baseline in 1-st group was – 141,21 ± 1.10 /85,63 ± 1.11 mm Hg and - 141,80 ± 1.32 /86,65 ± 1.33 mm Hg in 2-nd group. Decrease office blood pressure (SBP/DBP) in 1-st group was 35,69/16,52 mm Hg (p < 0,05) and in 2-nd group – 35,32/21,77 mm Hg (p < 0,05). There was increase the stiffness of the arterial wall in terms of cardio-vascular index CAVI in 2-d group without added statin. CAVI on the right/left site changed from 7.73 ± 0.26/7.62 ± 0.29 units to 8.63 ± 0.32/8.62 ± 0.32 units after treatment (p < 0,05). Cardio-vascular index (CAVI) in 1-st group with added statin was not changed. CAVI on the right/left site changed from 8.32 ± 0.16/8.33 ± 0.19 units to 8.44 ± 0.16/8.24 ± 0.15 units after treatment (p > 0,05). Conclusions: The added of statin to fixed combination antihypertensive therapy prevented the progression of arterial stiffness in patients with arterial hypertension.

OPTIMIZATION OF BLOOD PRESSURE CONTROL AND ANGIOPROTECTION WITH FIXED COMBINATION OF LISINOPRIL + AMLODIPINE + ROSUVASTATIN IN PATIENTS AFTER A COVID-19

Objective: Evaluation of the capability of a fixed combination of lisinopril + amlodipine + rosuvastatin (ECWAMER) in achieving additional angioprotection in patients with arterial hypertension (AH) and high pulse wave velocity (PWV) in patients after confirmed COVID-19 had 75 – 95% lung involvement, complicated by bilateral polysegmental viral pneumonia, with genetically engineered biological drugs (GIBD) therapy, who had not previously received combined antihypertensive therapy (AHT). Design and method: An open-label observational study with a duration of 12 weeks has been carried out. 30 patients who not previously received combined AHT was included. Patients underwent daily monitoring of blood pressure (ABPM), applanation tonometry (determination of the augmentation index (IA) and central blood pressure (CSAD)), measurement of PWV, laboratory tests (lipid composition of blood, fasting glucose, C-reactive protein - CRP, OAC, ferritin, fibrinogen, D-dimer, ALT, AST, creatinine, uric acid) before and after prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin (ECVAMER). Results: At baseline, the patients had an increase in office blood pressure to 152.6 / 89.1 mm Hg. After prescribing a fixed combination of lisinopril + amlodipine + rosuvastatin, there was a decrease in systolic blood pressure (SBP) by 15.8% and diastolic blood pressure (DBP) by 12.2%. According to ABPM data, the decrease in SBP was 15% and DBP - 9%, decreased PWV by 23.8%, IA by 9%, CSAP by 12.4% (p < 0.05 for all comparisons with the baseline value). Vascular age (SV) was initially increased to 41.9 years with a passport age of 35.03 years. After the end of therapy, there was a significant decrease in CO up to 36.5 years, LDL by 46.8%, triglycerides by 16.8% and an increase in HDL by 10.7% (p < 0.05 for all comparisons with the baseline value). In addition, the levels of CRP, fibrinogen, D-dimer, glucose, and uric acid significantly decreased. Conclusions: The fixed combination of lisinopril + amlodipine + rosuvastatin provides better blood pressure control, improved vascular elasticity, and also improves lipid and carbohydrate metabolism in patients, reduces inflammation in patients with hypertension and hyperlipidemia after suffering from severe and extremely severe COVID-19.

Clinical Characteristics of Hospitalized Pediatric Patients With Hypertensive Crisis-A Retrospective, Single-Center Study in China.

BackgroundA hypertensive crisis is a medical emergency that causes acute damage to multiple organs. However, the etiology, clinical features, and prognosis of hypertensive crisis in Chinese children remain relatively unknown. The purpose of this study was to analyze the clinical characteristics of pediatric hypertensive crisis patients from a single center in China.MethodsWe analyzed data from 70 children with hypertensive crisis between January, 2000, and January, 2022. The patients were divided into two groups: those diagnosed with a hypertensive emergency (n = 46) and those diagnosed with hypertensive urgency (n = 24). Baseline etiologies and risk factors were compared between the two groups. The following data were collected and analyzed: age, sex, weight, height, family history of hypertension, blood pressure, clinical manifestations of hypertensive crisis, underlying causes, biochemical indicators, and antihypertensive drugs.ResultsThe major symptoms of hypertensive crisis were headache (n = 31, 44.29%), followed by visual symptoms (n = 15, 21.43%), and dizziness (n = 13, 18.57%). Further analysis showed that the incidence of convulsions was significantly higher in patients with hypertensive emergency than those with hypertensive urgency (χ2 = 5.38, p = 0.02). The leading underlying causes were renal disease (n = 34, 48.57%), followed by vascular disease (n = 11, 15.71%), essential hypertension (n = 9, 12.86%), oncological disease (n = 9, 12.86%), central nervous system disease (n = 3, 4.29%), endocrine and metabolic diseases (n = 2, 2.86%), and other (one case with lead poisoning, one case with histiocytosis). End-organ damage occurred in 46 patients with hypertensive crisis, including retinal damage (n = 20, 43.48%), brain damage (n = 19, 41.30%), heart damage (n = 15, 32.61%), and renal damage (n = 3, 6.52%). Hypertensive crisis was most common among children aged 7–12 years. Among children aged 13–18 years, hypertensive urgency was more common than hypertensive emergency. The incidence of dyslipidemia, elevated serum creatinine, and elevated uric acid did not differ significantly between the two groups. Most patients with hypertensive crisis need combined antihypertensive therapy (n = 60, 85.71%). There were no cases of mortality.ConclusionsHypertensive crisis is caused by secondary diseases, especially renal disease and vascular disease, in the majority of pediatric patients. Combination therapy with antihypertensive agents and treatment of secondary etiology results in a good prognosis.

Arterial hypertension - clinical trials update 2022.

Hypertension is the most prevalent cardiovascular risk factor worldwide and is associated with increased cardiovascular morbidity and mortality. Despite the availability of multimodal therapeutic approaches, a large number of patients do not achieve guideline-recommended blood pressure targets, which reiterates the importance of continued research in the field. This article summarizes and discusses the most relevant clinical trials in hypertension research published in 2021 and 2022. The topics include new insights into treatment targets in the elderly, novel findings of salt consumption and lifestyle interventions in resistant hypertension, new evidence about early antihypertensive combination therapy and the use of angiotensin II receptor blocker neprilysin inhibitors in resistant hypertension, as well as data regarding the safety of antihypertensive drugs with respect to cancerogeneity and regarding the impact of acetaminophen, a commonly used pain medication, on blood pressure. Finally, we provide an update on recent evidence on renal denervation and its role in current hypertension management.

Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort

More than 1 billion adults have hypertension globally, of whom 70% cannot achieve their hypertension control goal with monotherapy alone. Data are lacking on clinical use patterns of dual combination therapies prescribed to patients who escalate from monotherapy. To investigate the most common dual combinations prescribed for treatment escalation in different countries and how treatment use varies by age, sex, and history of cardiovascular disease. This cohort study used data from 11 electronic health record databases that cover 118 million patients across 8 countries and regions between January 2000 and December 2019. Included participants were adult patients (ages ≥18 years) who newly initiated antihypertensive dual combination therapy after escalating from monotherapy. There were 2 databases included for 3 countries: the Iqvia Longitudinal Patient Database (LPD) Australia and Electronic Practice-based Research Network 2019 linked data set from South Western Sydney Local Health District (ePBRN SWSLHD) from Australia, Ajou University School of Medicine (AUSOM) and Kyung Hee University Hospital (KHMC) databases from South Korea, and Khoo Teck Puat Hospital (KTPH) and National University Hospital (NUH) databases from Singapore. Data were analyzed from June 2020 through August 2021. Treatment with dual combinations of the 4 most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; β-blocker; and thiazide or thiazide-like diuretic). The proportion of patients receiving each dual combination regimen, overall and by country and demographic subgroup. Among 970 335 patients with hypertension who newly initiated dual combination therapy included in the final analysis, there were 11 494 patients from Australia (including 9291 patients in Australia LPD and 2203 patients in ePBRN SWSLHD), 6980 patients from South Korea (including 6029 patients in Ajou University and 951 patients in KHMC), 2096 patients from Singapore (including 842 patients in KTPH and 1254 patients in NUH), 7008 patients from China, 8544 patients from Taiwan, 103 994 patients from France, 76 082 patients from Italy, and 754 137 patients from the US. The mean (SD) age ranged from 57.6 (14.8) years in China to 67.7 (15.9) years in the Singapore KTPH database, and the proportion of patients by sex ranged from 24 358 (36.9%) women in Italy to 408 964 (54.3%) women in the US. Among 12 dual combinations of antihypertensive drug classes commonly used, there were significant variations in use across country and patient subgroup. For example starting an ACEI or ARB monotherapy followed by a CCB (ie, ACEI or ARB + CCB) was the most commonly prescribed combination in Australia (698 patients in ePBRN SWSLHD [31.7%] and 3842 patients in Australia LPD [41.4%]) and Singapore (216 patients in KTPH [25.7%] and 439 patients in NUH [35.0%]), while in South Korea, CCB + ACEI or ARB (191 patients in KHMC [20.1%] and 1487 patients in Ajou University [24.7%]), CCB + β-blocker (814 patients in Ajou University [13.5%] and 217 patients in KHMC [22.8%]), and ACEI or ARB + CCB (147 patients in KHMC [15.5%] and 1216 patients in Ajou University [20.2%]) were the 3 most commonly prescribed combinations. The distribution of 12 dual combination therapies were significantly different by age and sex in almost all databases. For example, use of ACEI or ARB + CCB varied from 873 of 3737 patients ages 18 to 64 years (23.4%) to 343 of 2292 patients ages 65 years or older (15.0%) in South Korea's Ajou University database (P for database distribution by age < .001), while use of ACEI or ARB + CCB varied from 2121 of 4718 (44.8%) men to 1721 of 4549 (37.7%) women in Australian LPD (P for drug combination distributions by sex < .001). In this study, large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic group. These findings suggest that future research may be needed to investigate what dual combinations are associated with best outcomes for which patients.

A Differential Response to Antihypertensive Therapy in African Men and Women: Insights From the CREOLE Trial.

We sought to address the paucity of data to support the evidence-based management of hypertension to achieve optimal blood pressure (BP) control on a sex-specific basis in Africa. We undertook a post hoc analysis of the multicenter, randomized CREOLE (Comparison of Three Combination Therapies in Lowering Blood Pressure in Black Africans) Trial to test the hypothesis that there would be clinically important differences in office BP control between African men and women. We compared the BP levels of 397 and 238 hypertensive women (63%, 50.9 ± 10.5 years) and men (51.2 ± 11.3 years) from 10 sites across sub-Saharan Africa who completed baseline and 6-month profiling according to their randomly allocated antihypertensive treatment. Overall, 442/635 (69.6%) participants achieved an office BP target of <140/90 mm Hg at 6 months; comprising more women (286/72.0%) than men (156/65.5%) (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.07-2.39; P = 0.023). Women randomized to amlodipine-hydrochlorothiazide (HCTZ) (adjusted OR 3.03, 95% CI 1.71-5.35; P < 0.001) or amlodipine-perindopril (adjusted OR 2.62, 95% CI 1.49-4.58; P = 0.01) were more likely to achieve this target compared with perindopril-HCTZ. Among men, there were no equivalent treatment differences-amlodipine-HCTZ (OR 1.54, 95% CI 0.76-3.12; P = 0.23) or amlodipine-perindopril (OR 1.32, 95% CI 0.65-2.67; P = 0.44) vs. perindopril-HCTZ. Among the 613 participants (97%) with 24-hour ambulatory BP monitoring, women had significantly lower systolic (124.1 ± 18.1 vs. 127.3 ± 16.9; P = 0.028) and diastolic (72.7 ± 10.4 vs. 75.1 ± 10.5; P = 0.007) BP levels at 6 months compared with men. These data suggest clinically important differences in the therapeutic response to antihypertensive combination therapy among African women compared with African men.

Вплив моно- та комбінованої антигіпертензивної терапії на активність системного запалення у хворих на гіпертонічну хворобу

Метою дослідження є оцінка впливу моно- та комбінованої антигіпертензивної терапії на показники системного запалення (С-реактивний протеїн (СРП), інтерлейкін (ІЛ)-6 і фактор некрозу пухлини (ФНП) α у взаємозв’язку з динамікою характеристик добового профілю артеріального тиску.Обстежено 99 хворих на гіпертонічну хворобу І–ІІ стадії 1–2-го ступеня, які були рандомізовані в 3 групи терапії: 29 пацієнтів отримували монотерапію телмісартаном у дозі 40–80 мг/добу, 27 — S-амлодипіном у дозі 5 мг/добу та 43 — фіксовану комбінацію валсартану з амлодипіном у дозі 160/5 мг/добу). Визначення вмісту СРП, ІЛ-6 і ФНП-α проводили до початку (після 7-денного безмедикаментозного періоду) та після 6 міс. терапії.Було встановлено, що лікування телмісартаном сприяє зниженню сироваткового рівня СРП на 13,9 % та ІЛ-6 — на 36,4 %, проте не впливає на вміст ФНП-α у крові хворих на гіпертонічну хворобу. Монотерапія антагоністом кальцію S-амлодипіном призводить до зменшення вмісту в крові прозапальних цитокінів: ІЛ-6 — на 39 % та ФНП-α — на 11,9 %. Застосування фіксованої комбінації валсартану з амлодипіном чинить більш суттєвий антигіпертензивний ефект, проте це не супроводжувалося більш вираженим, ніж у групах монотерапії, зниженням СРП і ІЛ-6, що становило відповідно 12,5 і 31,5 %.Було виявлено, що зниження АТ прямо пов’язане зі зменшенням активності системного запалення. Так, зменшення сироваткового вмісту ФНП-α корелює зі зниженням систолічного та діастолічного АТ у всі періоди доби під впливом лікування, а зниження рівня СРП асоціюється зі змінами середньодобового та середньоденного систолічного артеріального тиску, його добового індексу та нічної варіабельності.Отримані нами дані засвідчують зменшення активності запалення низької градації під впливом блокаторів рецепторів ангіотензину ІІ (телмісартан) та антагоністів кальцію (S-амлодипін) як при монотерапії, так і при використанні їх комбінації (валсартан із амлодипіном), яке прямо корелює зі зниженням артеріального тиску за даними амбулаторних вимірювань.

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.

The Effects of Single Pill Combinations on Adherence and Blood Pressure Control in Hypertensive Patients.

Background:Hypertension is the most important risk factor for cardiovascular morbidity and mortality. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low-income countries. Blood pressure control rates are as low as 17% to 31% in patients diagnosed with hypertension in high-income countries; control rates are likely poorer in low- to middle- and low- income countries. Overall, 43% to 66% of patients fail to adhere to their prescribed antihypertensive medications, and after 1 year, ≈40% of patients with hypertension may stop their initial drug treatment.Objective:The aim of the study was to evaluate the effects of single pill combination antihypertensive drugs on the adherence to treatment, blood pressure control and cardiovascular events vs. free-combination therapy.Methods:We enrolled 192 adult hypertensive patients not older than 79 years, with untreated or uncontrolled hypertension despite previously receiving free combination antihypertensive therapy, between November 2020 and March 2022. Patients treated with single pill combination (SPC) were compared with an arm of the same size (n = 96) and matched by age and gender who received a standard free combination (FC) antihypertensive therapy.Results:There were significant reductions from baseline to month 6 of follow-up in office SBP in the SPC group vs. reduction in FC group (21.9 vs. 13.1 mmHg; p < 0.0001). There were significant reductions from baseline to month 6 of follow-up in office DBP in the SPC group vs. group with free-combination therapy (13.7 vs. 8.0 mmHg; p < 0.0001). At 6 months, 94 participants (98%) were still prescribed the SPC therapy. At the final 6-month study visit, 84.2% of patients in the SPC therapy group were adherent to the prescribed antihypertensive therapy vs. 52% of patients in the FC group. Target BP values (mean 24h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of SPC than free-combination therapy (78.2% vs. 46.3%, p < 0.05) at month 6 of follow-up.Conclusion:Treatment with single pill combinations (SPC), is the emerging best practice for safe, effective, rapid, and convenient hypertension control. It improves the affordability, adherence and control of arterial hypertension.

Effects of Posttrial Antihypertensive Drugs on Morbidity and Mortality: Findings from 15-Year Passive Follow-Up after ALLHAT Ended.

Background Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) ended in 2002, but it is important to study its long-term outcomes during the posttrial period by incorporating posttrial antihypertensive medication uses in the analysis. Purposes The primary aim is to explore the patterns of antihypertensive medication use during the posttrial period from Medicare Part-D data over the 11-year period from 2007 to 2017. The secondary aim is to examine the potential effects of these posttrial antihypertensive medications on the observed mortality and morbidity benefits. Methods This is a posttrial passive follow-up study of ALLHAT participants in 567 US centers in 1994–1998 with the last date of active in-trial follow-up on March 31, 2002, by linking with their Medicare and National Death Index data through 2017 among 8,007 subjects receiving antihypertensive drugs (3,637 for chlorthalidone, 2,189 for amlodipine, and 2,181 for lisinopril). Outcomes included posttrial antihypertensive drug use, all-cause mortality, and cardiovascular disease (CVD) mortality. Results Of 8007 subjects, 3,637 participants were initially randomized to diuretic (chlorthalidone). The majority (67.9%) of them still received diuretics in 2007, and 52.7%, 47.2%, and 44.0% received β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs), respectively. Compared to participants who received diuretic-based antihypertensives, those who received CCB had a nonsignificantly higher risk of all-cause mortality (1.17, 0.99–1.37), whereas those who received ACE/ARB (angiotensin receptor blockers) had a significantly higher risk of all-cause mortality (1.26, 1.09–1.45). For the combined fatal or nonfatal hospitalized events, the risk of CVD was significantly higher in patients receiving CCB (1.30, 1.04–1.61) and ACE/ARB (1.49, 1.22–1.81) as compared to patients receiving diuretics. Conclusion After the conclusion of the ALLHAT, almost all patients switched to combination antihypertensive therapies, independently by the original drug class, and the combination therapies (mostly based on diuretics) reduced the incidence of major cardiovascular outcomes and mortality.

Organoprotective properties of combination therapy with ramipril and indapamide in hypertensive patients with non-alcoholic fatty liver disease

Objective. To assess the effect of combined antihypertensive therapy with ramipril and indapamide on the structural and functional state of the heart, blood vessels, kidneys, autonomic nervous system and liver in hypertensive patients with non-alcoholic fatty liver disease (NAFLD). Design and methods. We performed a prospective controlled study including 30 patients with hypertension (HTN) stages I–II, 1–2 degrees with NAFLD (fatty liver index (FLI) &gt; 60) aged 45 to 65 years. Five-seven days before the initial examination, patients discontinued antihypertensive drugs, after the washout period one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg) was prescribed depending on the required dosage and recommendations on lifestyle changes and weight loss were given. Clinical examination, measurement of “office” blood pressure (BP), ambulatory BP monitoring (ABPM), central aortic pressure (CAP), pulse wave velocity (PWV), echocardiography and heart rate variability assessment were performed. The functional state of the kidneys and the structural and functional state of the liver were also assessed before and after treatment. Results. After 24-week therapy with a fixed combination of ramipril and indapamide (an average dosage 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively) target BP levels was achieved. According to ABPM, both daytime and nocturnal systolic BP (SBP) and diastolic BP (DBP) decreased. In addition, CAP (SBPao, DBPa) and augmentation index decreased. There was also a decrease in the stiffness of the arterial wall in muscle-type vessels (PWVm) (p = 0,0166) and in the number of patients with paradoxical test (p = 0,0320). There was a significant increase in creatinine clearance (Cockroft–Gault) after treatment (p = 0,0439) with no increase in glomerular filtration rate (CKD-EPI) (p = 0,1617). There was a significant change in the structural and functional indicators of the heart: increased left ventricular (LV) ejection fraction (p = 0,0398), decreased LV posterior wall thickness (p = 0,0457), LV end-systolic diameter (p = 0,0286), relative wall thickness (p = 0,0419) and LV myocardial mass index (p = 0,0002). There was a decrease in SDNN &lt; 50 (p &lt; 0,0001) and increase in RMSSD (p &lt; 0,0001), which indicates a decrease in the sympathetic activity and an increase in parasympathetic regulation. Also the number of patients with normotonic type of autonomic reactivity in the orthostatic test increased after treatment (12 (24,0%) vs 19 (63,3%), p = 0,0456). The liver function and structure also improved showing decrease in total bilirubin (p = 0,0038) and gamma-glutamyltransferase (p = 0,0498), as well as the indices of liver steatosis (p = 0,0278) and fibrosis (p = 0,0166). Conclusions. Thus, combined antihypertensive therapy with ramipril and indapamide is well tolerated by patients, highly effective and demonstrates organoprotective properties regarding the heart, blood vessels, kidneys, autonomic nervous system and liver.

Simultaneous Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC-MS/MS

Introduction. Combined drugs have the greatest efficacy and safety in arterial hypertension treatment. The combination of candesartan and hydrochlorothiazide (AT1-receptor antagonist and a thiazide diuretic, respectively) provides high efficiency of antihypertensive combination therapy, therefore it is widely used in medical practice. Developing a method for simultaneous determination of candesartan and hydrochlorithiazide in human blood plasma is necessary for performing the analytical part of pharmacokinetic studies and bioequivalence studies of multicomponent drugs.Aim. The aim of this study is to develop a method for quantitative determination of candesartan and hydrochlorothiazide in human plasma by high-performance liquid chromatography – tandem mass spectrometry (HPLC-MS/MS) for further bioequivalence studies.Materials and methods. Determination of candesartan and hydrochlorothiazide in human plasma by HPLC-MS/MS. The samples were processed by acetonitrile protein precipitation. Internal standard: mixed solution of valsartan and indapamide. Mobile phase: 0.1 % formic acid solution in water (eluent A), 0.1 % formic acid in acetonitrile (eluent B). Column: Phenomenex Luna Phenyl-Hexyl, 50x4.6 mm, 5 μm. Analytical range: 2.00– 300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. Ionization source: electrospray ionization. Detection conditions: 441.10 → 192.00 m/z, 441.10 → 263.15 m/z (candesartan), 295.85 → 269.00 m/z (hydrochlorothiazide), 436.00 → 207.05 m/z (valsartan), 363.85 → 132.10, 363.85 → 189.00 m/z (indapamide).Results and discussion. This method was validated by selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, the lower limit of quantification, carry-over effect and stability. The developed method meets the requirements for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union.Conclusion. The analytical range was 2.00–300.00 ng/mL for candesartan, 2.00–200.00 ng/mL for hydrochlorothiazide in human plasma. The method was applied in BE study of the combination of candesartan and hydrochlorothiazide.

Hypertension and diabetes mellitus: a collision of two heavyweight non-communicable diseases

Introduction: Patients living with type 2 diabetes mellitus (PLWD) are at an increased risk of developing hypertension (HPT). The presence of HPT in PLWD (PLWDH) accelerates diabetes-related complications (DRC). Scarce data exist from South Africa on the impact of HPT in PLWD. Methods: Data werecaptured from Edendale Hospital diabetes clinic datasheets from January 1, 2019 to December 31, 2019 and analysed to determine differences in demographic, clinical and biochemical variables between PLWD and PLWDH. Results: Data from 822 PLWD were analysed, the majority having HPT (71,386.74%). The prevalence of HPT, resistant HPT (RHPT) and the number of antihypertensives used increased with age and diabetes duration. PLWDH had statistically poorer lipid control (LC), higher creatinine, waist circumference (WC), increased prevalence of sensory peripheral neuropathy, non-proliferative and proliferative retinopathy, cerebrovascular accidents, proteinuria and renal impairment. The significant majority of PLWDH were not meeting diabetes targets (glycaemic, lipid, BMI, WC). The bulk of PLWDH were on combination antihypertensive therapy (p < 0.001) and performed significantly better than monotherapy for glycaemia, LC, BMI and WC. Proteinuria and blood pressure (BP) improved significantly as the number of antihypertensives increased. One-fifth (151, 18.37%) of PLWDH had RHPT;this was more common in females (p < 0.001). PLWD with RHPT had a significantly higher LDL cholesterol, BMI, and urine protein-creatinine ratio (p < 0.001). Over one-quarter (29.87%) of the PLWD without HPT had a BP over 140/90mmHg. Conclusion: It was shown that HPT, RHPT and obesity are significant comorbidities in PLWD and increase the risk of DRC. The majority of PLWDH are not meeting targets, which places them at increased risk of DRC. BP, glycaemic and LC and proteinuria improved in those on combination antihypertensive therapy. A significant proportion of PLWD without HPT had elevated BP, and thus were potentially undiagnosed hypertensives needing intervention.

AMBULATORY BLOOD PRESSURE MONITORING INDICATORS IN MIDDLE-AGED AND ELDERLY HYPERTENSIVE PATIENTS UNDER COMBINED ANTIHYPERTENSIVE THERAPY

It is known that arterial hypertension affects 30-35% of adult population of industrialized countries, and its prevalence reaches 40-50% among the elderly. In recent years, the issue of optimizing of treatment of hypertension in elderly people has been discussed such as choice of effective antihypertensive drugs with the least number of side effects, prevention of complications, reduced mortality, improvement of quality of life.&#x0D; The aim of the study was to substantiate the antihypertensive efficacy of the combination of enalapril and amlodipine in middle-aged and elderly hypertensive patients.&#x0D; Material and methods. Indices of ambulatory blood pressure monitoring were identified in 57 middle-aged patients (45-59 years) (group I) and 43 elderly patients (60-74 years) (group II), who underwent two-week in-patient treatment. All patients received the combined antihypertensive therapy (enalapril 10 mg twice daily and amlodipine 5 mg daily) for 2 weeks. And they were divided into 2 groups of 24 hours day's profile of blood pressure: dippers and non-dippers.&#x0D; Results. The combination of enalapril and amlodipine in elderly patients reduced the average daily diastolic blood pressure by 20,3% (p&lt;0,05). Instead, in middle-aged patients there was the decrease in the average daily and the maximal daily systolic blood pressure by 17,3% (p&lt;0,001) and 7,8% (p&lt;0,05) and diastolic blood pressure respectively − by 23,2% (p&lt;0,001) and 11,8% (p&lt;0,05).&#x0D; Conclusions. Therefore, combined antihypertensive therapy in the elderly for 14 days was insufficient to improve significantly ambulatory blood pressure monitoring indicators. Obviously, positive changes require longer treatment.

Metabolic effects of ramipril and indapamide in hypertensive patients with non-alcoholic fatty liver disease

Objective. To assess the effects of combined antihypertensive therapy with ramipril and indapamide on insulin resistance, carbohydrate, lipid and purine metabolism, as well as the structure and function of the liver in hypertensive patients with non-alcoholic fatty liver disease (NAFLD).Design and methods. In a pre-post study, we included 30 patients with hypertension (HTN) 1–2 degrees in combination with NAFLD (Fatty Liver Index (FLI) &gt; 60) aged 45 to 65 years. Patients discontinued antihypertensive therapy 5–7 days before the initial examination. After that one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg) were prescribed along with the lifestyle and weight reduction recommendations (the Mediterranean type of diet, a decrease in calorie intake by 500–1000 kcal from baseline, and physical aerobic exercise at least 150 minutes per week). All patients underwent clinical examination, measurement of office blood pressure (BP), ambulatory BP monitoring (ABPM), anthropometric parameters, assessment of the visceral obesity index (VAI), anthropometric parameters, VAI, the degree of adipose tissue dysfunction (ATD), the percentage of visceral and subcutaneous fat by the bioelectrical impedance method. We also assessed lipid, carbohydrate, purine metabolism and the structural and functional state of the liver before and after the treatment.Results. After 24-week therapy with a fixed combination of ramipril and indapamide (average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively) HTN patients with NAFLD achieved target BP. There was a decrease in both office systolic BP (SBP) (p &lt; 0,001) and office diastolic BP (DBP) (p = 0,007) in 100 % of patients, as well as in ABPM indices. We observed a decrease in waist and hip circumferences (p ≤ 0,001 and p ≤ 0,001, respectively), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,002) fat. The number of patients with normal ATD increased (p = 0,030), while the proportion of patients with dysfunction decreased (p = 0,039). There was also a significant increase in high-density lipoprotein cholesterol (p = 0,027) and a decrease in insulin resistance (p = 0,002) and metabolic index (p = 0,030). We also found an improvement in carbohydrate metabolism with no change in purine metabolism. There was a favorable effect on the liver structure and function, and the number of patients with high alaninaminotransferase &gt; 40 U/L decreased (5 (16,7 %) vs 0, p = 0,026).Conclusions. Twenty-fourweek treatment with a fixed combination of ramipril and indapamide, together with recommendations for lifestyle changes and weight loss, led to a significant decrease in BP levels, the severity of insulin resistance, and visceral obesity. In addition, the treatment had a beneficial effect on the parameters of carbohydrate and lipid metabolism, as well as liver structure and function (decreased severity of steatosis and fibrosis).

Association of decreased glomerular filtration rate with renal hemodynamic disorders and inflammatory biomarkers in patients with medically-controlled hypertension of high cardiovascular risk

Aim. To assess markers of chronic kidney disease (CKD) in patients with medically-controlled hypertension (HTN) (&lt;140/90 mm Hg), as well as to analyze potential association of decreased glomerular filtration rate (GFR) &lt;60 ml/min/1,73 m2 with clinical data and therapy; to establish significant determinants of GFR decrease in this category of patients.Material and methods. The study included 70 patients with HTN and office blood pressure (BP) &lt;140/90 mm Hg aged 64 (57; 68) years (men, 48,6%), of whom 40 patients were examined within the Russian multicenter CHRONOGRAPH program. Office BP was 130 (120; 140)/80 (72; 82) mm Hg. GFR and albuminuria were assessed. Twenty-four-hour BP monitoring and Doppler ultrasound of renal blood flow with estimation of resistance indices (RI) were performed. The content of highsensitivity C-reactive protein (hsCRP), interleukins (IL) 1β, 6, 10 and lipid transport function parameters was determined.Results. CKD markers were detected in 31,4% of patients (in 27,1% — a decrease in GFR &lt;60 ml/min/1,73 m2; in 12,9% — pathological albuminuria). Patients with CKD markers were older, had higher office systolic BP and nocturnal pulse pressure, higher blood hsCRP and RI levels throughout the renal flow, and lower high-density lipoprotein cholesterol levels. In the presence of CKD markers, calcium channel blockers, aldosterone receptor antagonists and statins were used more often. The results of correlation analysis were used to determine the determinants of GFR decline. In the general group, GFR values had inverse correlations with age (Rs=-0,58, p&lt;0,0001), segmental intrarenal artery RI (Rs= -0,4232, p=0,0005), blood hsCRP (Rs=-0,3998, p=0,0007), IL-1β (Rs=-0,3139, p=0,0086), office BP and some 24-hour BP parameters. In the presence of CKD markers, a direct association of GFR and IL-10 was determined (Rs=0,4293, p=0,046). In the absence of such markers, GFR had an inverse correlation with IL-1β content (Rs=-0,3110, p=0,0333). A multiple linear regression model included following independent determinants of GFR: age, blood hsCRP and RI in the segmental intrarenal arteries.Conclusion. Among patients with medically-controlled HTN of high cardiovascular risk, a high prevalence of CKD markers was revealed (31,4%). Compared with patients with preserved renal function, in the presence of CKD markers, there were higher levels of office systolic BP, nocturnal pulse pressure, blood hsCRP, and intrarenal artery RI. Associations were established between GFR and the levels of hsCRP, IL-1β and IL-10, which confirms the pathological role of inflammatory biomarkers in developing renal dysfunction in high-risk HTN. Age, elevated blood hsCRP levels, and intrarenal artery RI are independent determinants of decreased GFR in patients with medically-controlled HTN of high and very high cardiovascular risk. The data obtained shows the need for early prescription of combination antihypertensive therapy with nephro- and vasoprotective effects in this category of patients, as well as with an ability to depress the chronic subclinical inflammation.

Hemodynamic effects of combined antihypertensive therapy during exercise in men with arterial hypertension and chronic venous diseases

Introduction. Currently, there is insufficient data on the effect of modern antihypertensive therapy (AHT) on venous circulation, especially during physiological stress.Aim of the study – the investigation was to study the hemodynamic effects of a combination of a calcium channel blocker (CCB) and an angiotensin-converting enzyme (ACE) inhibitor during exercise in men with arterial hypertension (AH) and chronic venous diseases (CVD).Material and methods. In 46 men 30–50 years old with AH on the background of AHT, a comparative assessment of the dynamics of SBP, DBP, peripheral venous pressure (PVP), ultrasound parameters of venous blood flow of the left leg in response to physical activity (Ruffier’s test) was performed. The parameters were assessed in 23 patients with hypertension without CVD and 23 patients with hypertension and CVD. We studied the reaction before and after 14 days of combined AHT with the use of CCB (Amlodipine) and an ACE inhibitor (Lisinopril).Results. Before treatment, the response to exercise in patients of both groups was the same and was manifested by a twofold increase in the area of the lumen of the veins and a drop in blood flow velocity. Patients with CVD before treatment with exercise were characterized by an altered systemic hemodynamic response, more frequent cases of venous dilatation and decreased blood flow velocity. After AHT with exercise, both groups showed normalization and identity of SBP. DBP, PVP, a decrease in the severity of venous dilatation and a decrease in blood flow velocity. Patients with CVD after AHT in response to exercise are characterized by more pronounced venous dilatation and higher blood flow velocity.Conclusion. After 14 days of antihypertensive therapy in patients with hypertension without chronic venous disease and in patients with hypertension and chronic venous disease during exercise normalization of systolic blood pressure, diastolic blood pressure, PVP, a decrease in venous dilatation and a decrease in blood flow velocity are noted. Patients with CVD after AHT under load are characterized by varicose veins and accelerated venous blood flow.

Factors associated with antihypertensive monotherapy among US adults with treated hypertension and uncontrolled blood pressure overall and by race/ethnicity, National Health and Nutrition Examination Survey 2013-2018

Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.