Antihypertensive Efficacy Research Articles

Effects of Chronic Intractable Insomnia on Inflammatory Cytokines, Blood Pressure Characteristics, and Antihypertensive Efficacy in Hypertensive Patients.

BackgroundThis study investigated the changes in blood pressure and inflammatory cytokines in patients with chronic intractable insomnia, and explored the effects of chronic intractable insomnia on antihypertensive efficacy.Material/MethodsA total of 248 patients with hypertension admitted to our hospital from 2008 to 2017 were enrolled. We enrolled 124 patients without chronic insomnia in the control group, while 124 patients with chronic insomnia were included in the treatment group. The treatment group received estazolam and was further subdivided into the effective group (n=96) and the ineffective group (n=28) according to Sleep Dysfunction Rating Scale (SDRS) scores. Sleep quality before and after treatment was determined.ResultsAntihypertensive treatment with eplerenone (50 mg) significantly reduced SDRS scores, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), serum intercellular adhesion molecules (sICAM), and IL-1β levels, as well as systolic blood pressures (SBP) and diastolic blood pressures (DBP), with elevation of non-dipper blood pressure rhythm (P<0.05). The inhibition of intractable insomnia significantly downregulated SBP and DBP, as well as serum inflammatory cytokines such as CRP and TNF-α, showing a favorable effect on antihypertensive function.ConclusionsAlleviation of chronic intractable insomnia facilitates hypertension therapy through decreasing levels of inflammatory cytokines and the proportion of non-dipper blood pressure rhythm, which offers insights for the treatment of hypertension.

Fixed combinations in modern hypertension treatment algorithms

Modern appropriate treatment of hypertension involves the use of combination antihypertensive therapy. According to updated version of European Society of Cardiology 2018 guidelines, renin-angiotensin-aldosterone system blockers must be used as first-line drugs, including in combination with hydrochlorothiazide. This article presents the algorithms for the management of patients with uncomplicated and asymptomatic (with target lesions) arterial hypertension. It also described the management of patients with concomitant cardiovascular, cerebrovascular, renal pathology and diabetes mellitus, and use of fixed combination of candesartan and hydrochlorothiazide. The article presents research data that confirmed not only the high antihypertensive efficacy of this combination, but also demonstrated its neutral metabolic profile, organ-protective effects, the ability to use in patients with chronic kidney disease, chronic heart failure, prior stroke, as well as high tolerability and treatment adherence.

Nitrendipine and Dementia: Forgotten Positive Facts?

Nowadays, there are about 50 million people suffering from dementia worldwide. In 2030, it is expected that there will be 82 million people living with dementia and in 2050, their number should reach 152 million. This increase in the number of people with dementia results in significant social and economic problems. Therefore, researchers attempt to reduce risk factors causing the development of dementia such as high blood pressure. Epidemiological studies have shown that hypertension increases the risk of dementia at an older age. It can, therefore, be assumed that hypertension therapy will reduce the risk of dementia. However, previous clinical studies have shown that the efficacy of different antihypertensive drugs differs in this respect. The drug group that appears to be the most effective in these analyses is calcium channel blockers (CCBs). The most significant preventive efficacy in terms of protection against dementia has been demonstrated with nitrendipine. Its use is, therefore, particularly advantageous in elderly patients with systolic hypertension who are at high risk of dementia. The purpose of this study is to restore the discussion on the prevention of vascular dementia and Alzheimer’s dementia with nitrendipine in indicated hypertonic patients. The authors performed a literature search of available sources describing the issue of dementia, hypertension and its treatment with nitrendipine. In addition, they made a comparison and evaluation of relevant findings. The results of the detected research studies indicate that nitrendipine is able to reduce the incidence of dementia [Alzheimer’s disease (AD), vascular and mixed] by 55%. The treatment of 1,000 patients with nitrendipine for 5 years may prevent 20 cases of dementia. However, what has not yet been explained is the temporal link between hypertension and dementia due to the long-time intervals between hypertension and the development of dementia.

Angiotensin receptor blockers: rational prescription tailored to the cardiovascular risk and comorbidities

Renin­angiotensin­aldosterone axis activation is an important mechanism of hypertension and its cardiovascular and renal complications. Angiotensin receptor blockers are considered among the first­choice antihypertensive drugs in Russia, European countries, and the USA. In addition to antihypertensive action, these drugs positively influence several components of the cardiovascular continuum and can be used for individualized management of high cardiovascular risk patients. The paper discusses the benefits of angiotensin receptor blockers use in patients with cardiovascular comorbidities. The paper includes a clinical case scenario revealing antihypertensive efficacy of telmisartan as an initial agent in a patient with high risk of cardiovascular events.

Discovery of TD-0212, an Orally Active Dual Pharmacology AT1 Antagonist and Neprilysin Inhibitor (ARNI).

Dual inhibition of angiotensin-converting enzyme (ACE) and neprilysin (NEP) by drugs such as omapatrilat produces superior antihypertensive efficacy relative to ACE inhibitors but is associated with a higher risk of life-threatening angioedema due to bradykinin elevations. We hypothesized that dual AT1 (angiotensin II type 1 receptor) blockade and NEP inhibition with a single molecule would produce similar antihypertensive efficacy to omapatrilat without the risk of angioedema since ACE (the rate limiting enzyme in bradykinin metabolism) would remain uninhibited. Merging the structures of losartan (an AT1 antagonist) and thiorphan (a NEP inhibitor) led to the discovery of a novel series of orally active, dual AT1 antagonist/NEP inhibitors (ARNIs) exemplified by compound 35 (TD-0212). In models of renin-dependent and -independent hypertension, 35 produced blood pressure reductions similar to omapatrilat and combinations of AT1 receptor antagonists and NEP inhibitors. Upper airway angioedema risk was assessed in a rat tracheal plasma extravasation (TPE) model. Unlike omapatrilat, 35 did not increase TPE at antihypertensive doses. Compound 35 therefore provides the enhanced activity of dual AT1/NEP inhibition with a potentially lower risk of angioedema relative to dual ACE/NEP inhibition.

ФАРМАКОЭКОНОМИЧЕСКИЙ АНАЛИЗ АНТИГИПЕРТЕНЗИВНЫХ ПРЕПАРАТОВ, НАЗНАЧАЕМЫХ ПАЦИЕНТАМ ПЕНСИОННОГО ВОЗРАСТА, ПРОЖИВАЮЩИМ НА ДОНБАССЕ, СТРАДАЮЩИМ ГИПЕРТОНИЧЕСКОЙ БОЛЕЗНЬЮ

Цель работыОценить затраты на фармакотерапию больными гипертонической болезнью пенсионного возраста, принимавших участие в программе повышения комплаентности, используя метод фармакоэкономического анализа «затраты-эффективность» антигипертензивных лекарственных препаратов зарубежного и российского производства.Материал и методыПроанализировано лечение 114 больных гипертонической болезнью пенсионного возраста, проживающих в Донбассе. Все пациенты получали комбинированную фармакотерапию: 42 человека – препараты российского и импортного производства (фармакотерапия таких больных не подвергалась фармакоэкономическому анализу). Остальные 72 пациента принимали только российские (40 человек), либо только импортные препараты (32 человека). У этих больных были проанализированы дневники, в которых они регистрировали приём препаратов и уровень артериального давления. Для проведения фармакоэкономического анализа, был выбран анализ «затраты-эффективность».Результаты и обсуждениеУ 72 пациентов, которые принимали только российские, либо только импортные антигипертензивные лекарственные препараты использовались следующие комбинации фармакологических групп: ингибиторы ангиотензин-превращающего фермента + мочегонное (30 человек); бета-адреноблокаторы + блокаторы кальциевых каналов (19 человек); блокаторы ангиотензиновых рецепторов + мочегонное (23 человека).Анализ индивидуальных дневников показал, что пациенты регулярно принимали антигипертензивные лекарственные препараты (согласно назначениям врача), а самоконтроль лечения обеспечивал эффективное снижение артериального давления.Фармакоэкономический анализ «затраты-эффективность» показал, что с увеличением стоимости препаратов импортного производства у больных гипертонической болезнью пенсионного возраста более выражено снижается систолическое артериальное давление (R=0,678, при p=0,022). В группе больных, принимающих российские генерики, связи снижения систолического артериального давления со стоимостью препарата не выявлено (R=0,483, при p=0,131). Коэффициент эффективности затрат для импортных препаратов составляет 68,8±33,4 руб./мм рт.ст., а для российских генериков 11,7±8,3 руб./мм рт. ст.Заключение Впервые, при непосредственном участии провизора, в Донбассе была организована программа повышения комплаентности больных гипертонической болезнью пенсионного возраста. Консультативная помощь провизора посетителям аптеки в вопросах соблюдения режима приёма антигипертензивных лекарственных препаратов, а также приобретении пациентами лекарств, в соответствии с их финансовыми возможностями, позволила оптимизировать лечение больных гипертонической болезнью (повышение комплаентности и достижение целевого артериального давления). Фармакоэкономический анализ антигипертензивных лекарственных препаратов, назначаемых больным гипертонической болезнью пенсионного возраста, проживающих в Донбассе, с применением метода «затраты-эффективность» показал, что использование больными лекарств российского и импортного производства обеспечивает сопоставимую антигипертензивную эффективность; при этом существенно меньшие затраты на лечение отмечаются при использовании препаратов российского производства.

Outcome of Bevacizumab Therapy in Patients with Recurrent Glioblastoma Treated with Angiotensin System Inhibitors

ABSTRACTPurpose: Antihypertensive therapy may improve bevacizumab efficacy in cancer patients. We examined efficacy and toxicity of angiotensin system inhibitors (ASI) and other antihypertensive drugs in bevacizumab treated recurrent glioblastoma patients.Methods: We retrospectively combined a national prescription registry with a clinical database with recurrent glioblastoma patients (n = 243).Results: Patients who initiated ASI after bevacizumab (n = 26) showed a tendency towards improved progression-free survival and overall survival (OS) with hazard rate (HR) reductions (HR = 0.70 and HR = 0.79, respectively). Calcium antagonists during bevacizumab therapy significantly improved OS (HR = 0.57).Conclusions: Overall the study supports a potential beneficial effect of antihypertensive treatment on prognosis of bevacizumab treated glioblastoma patients.

Antihypertensive Efficacy of a Triple Fixed-Dose Combination of Perindopril, Indapamide, and Amlodipine: Clinical Effectiveness in Ambulatory Practice (Results of the PETRA Study)

Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30 % of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6 % women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10 / 91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47 / 11.41±9.90 mm Hg (p&lt;0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5 / 1.25 / 5, 10 / 2.5 / 5, and 10 / 2.5 / 10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43 / 85.28±11.48 down to 134.63±12.51 / 77.83±8.99 mm Hg (p&lt;0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4 %, respectively], triglycerides [-12,1 %], fasting blood glucose [-6.6 %]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.

Fixed combination of amlodipine/indapamide-retard in the treatment of uncontrolled hypertension in subjects over 55 years old

Objective . To evaluate the antihypertensive efficacy and safety of a fixed combination of amlodipine/indapamideretard in patients with uncomplicated uncontrolled arterial hypertension (HTN) in the older age group. Design and methods . We included 40 patients (average age — 62 years, men — 20 %, mean HTN duration — 9 years) with uncomplicated uncontrolled HTN in an open, single-center study. Fixed-combination therapy with amlodipine/indapamide-retard (5/1,5 mg) once a day for 4 weeks were prescribed. After 4 weeks, in patients who did not reach the target blood pressure (BP), the dose increased from 5/1,5 to 10/1,5 mg. The follow-up period was 12 weeks. Results . The initial systolic BP (SBP) was 165 [148; 171] mm Hg, diastolic BP (DBP) — 96 [80; 102] mm Hg. After a 12-week therapy with a fixed combination of amlodipine/indapamide-retard, SBP decreased by 31 mm Hg, DBP — by 17 mm Hg. Target clinical BP (< 140/90 mm Hg in patients without diabetes mellitus (DM), < 140/85 mm Hg in patients with diabetes mellitus) was achieved in 93 % patients. Central SBP measured by applanation tonometry decreased by 16 mm Hg, DBP — 10 mmHg, pulse pressure — 6 mmHg. Prior to treatment, the median of carotid-femoral pulse wave velocity (cfPWV) was 11,1 [7,8; 14,5] m/sec. After 12 weeks there was a decrease in cfPWV to 8,9 [6,7; 12,6] m/sec (p < 0,05 in comparison with the baseline). Conclusions . Fixed combination of amlodipine/thiazide-like diuretic in patients with uncomplicated uncontrolled 1–2 degree HTN has a high antihypertensive efficacy, allowing achievement of target BP in 93 % patients after 12-week therapy, with a satisfactory safety profile and metabolic neutrality. We showed the ability of a combination of amlodipine/indapamide-retard to reduce central SBP, pulse pressure in the aorta, and cfPWV.

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes life-style interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipid-lowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population.

Evaluation of antihypertensive efficacy of Losartan + Hydrochlorthiazide versus Telmisartan + Hydrochlorthiazide in patients with stage 1 or stage 2 hypertension: a randomized controlled trial

Background: Cardiovascular disease (CVD) is the most common contributor of morbidity and mortality in underdeveloped and developing countries including the South Asian countries (including India and Pakistan). Amongst the cluster group of CVDs, Hypertension (HTN) represents the most common cardiovascular risk factor. The aim of this trial was to evaluate of antihypertensive efficacy and effect on biochemical parameters of Losartan + Hydrochlorthiazide versus Telmisartan + Hydrochlorthiazide in patients with stage 1 or stage 2 hypertension with a randomized controlled trial.Methods: This was a prospective, randomized controlled trial of Losartan + Hydrochlorthiazide versus Telmisartan + Hydrochlorthiazide in patients with stage 1 or stage 2 hypertension. The primary endpoint on treatment was analysis of antihypertensive efficacy of these drug combinations. The variables were compared at different time points- baseline, 3 and 6 months.Results: In the present study, 76 patients were enrolled with 38 patients each allocated to each treatment groups. The effect of Losartan 50mg + Hydrochlorthiazide 12.5mg OD was found to be significant on SBP and DBP in both supine as well as sitting position than Telmisartan 80mg + Hydrochlorthiazide 12.5mg OD group at 3 and 6 months.Conclusions: The results on anti- hypertensive efficacy was far better in Losartan 50mg + Hydrochlorthiazide 12.5mg OD group than Telmisartan 80mg + Hydrochlorthiazide 12.5mg OD group.

A5808 The relationship between CYP2C9 *1/*3 and AGTR1 1166A/C polymorphisms in hypertensive patients in Xinjiang Kazakh and Uygur and the relationship between angiotensin II receptor antagonists and antihypertensive efficacy

A5808 The relationship between CYP2C9 *1/*3 and AGTR1 1166A/C polymorphisms in hypertensive patients in Xinjiang Kazakh and Uygur and the relationship between angiotensin II receptor antagonists and antihypertensive efficacy

A13091 Impact of ACE2 gene polymorphism on antihypertensive efficacy of ACE inhibitors

Objectives: Angiotensin-converting enzyme 2 (ACE2), a newly discovered member of renin-angiotensin-aldosterone system, counterbalances the actions of angiotensin-converting enzyme. Methods: The objective of our study was to assess the association between rs2106809 polymorphism in ACE2 gene and the blood pressure response to ACE inhibitors in untreated hypertensive patients. After a 2-week, double-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 497 patients with mild to moderate essential hypertension. Results: The achieved changes in BP were analyzed for their association with genotypes at ACE2 gene loci. In female hypertensive patients, the genotype frequency of ACE2 rs2106809 was 36.7%, 45.2% and 18.1% for CC, CT and TT genotypes, respectively. After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (9.62 ± 6.83 or 10.2 ± 7.2 versus 6.81 ± 6.31 mmHg, respectively; P = 0.045, analysis of variance (ANOVA)). Moreover, the reductions in mean arterial pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (12.1 ± 7.5 or 12.0 ± 7.9 versus 8.38 ± 6.83 mmHg, respectively; P = 0.035, ANOVA). In male hypertensive patients, the genotype frequency of ACE2 rs2106809 was 58.1% and 41.9% for C and T genotypes, respectively. However, no association could be observed in males. Conclusion: We conclude that ACE2 rs2106809 is an important predictive factor of the response to antihypertensive treatment with ACE inhibitors in Chinese female hypertensive patients.

A comparative study of antihypertensive efficacy and perinatal safety of intravenous hydralazine and labetalol in pregnancy induced hypertensive crisis

A comparative study of antihypertensive efficacy and perinatal safety of intravenous hydralazine and labetalol in pregnancy induced hypertensive crisis

P1865Non-steroid anti-inflammatory drug consumption decrease antihypertensive treatment efficacy in postenopausal women

P1865Non-steroid anti-inflammatory drug consumption decrease antihypertensive treatment efficacy in postenopausal women

Blood pressure level and arterial stiffness parameters role in prediction of the antihypertensive therapy efficacy escape phenomenon

The aim of the study was to evaluate blood pressure (BP) level and vessel wall stiffness parameters role in antihypertensive therapy (AHT) escape phenomena development on the background of primarily effective AHT use. Materials and methods. Data from 102 patients with arterial hypertension level 1-3, stage I-II were analyzed. All patients underwent individual AHT adjustment for 2-3 weeks (adjustment period). At the end of the adjustment period the therapy effectiveness was evaluated with clinical BP measurement (target BP values less than 140/90 mm hg) and 24-hour BP monitoring (target daily BP values less than 130/80 mm hg). The study included only those patients who reached target clinical and daily BP values on the background of 2-3 antihypertensive drugs use at the end of the adjustment period. At the beginning of the observation period after effective AHT was used carotid-femoral pulse wave velocity was evaluated with applanation tonometry. For the purpose of timely escape phenomena diagnosis clinical BP measurement and 24-hour BP monitoring were performed in 1, 3, and 6 months after the trial start in all patients. Results. After 6 months of observation patients were divided in 2 groups: group 1 included 34 patients with AHT escape phenomena, group 2 - 68 patients with stable, controlled AH. In group 1 on the background of effective AHT use at the beginning of observation higher levels of following measures were observed: clinical systolic BP - SBP (125.2±11.3 mm hg vs 119.7±11.7 mm hg, p=0.021), daily SBP (128.0±3.3 mm hg vs 121.2±7.4 mm hg, p=0.000), daily average SBP (131.6±4.9 mm hg vs 125.3±8.5 mm hg, р=0.000), night average SBP (120.4±8.5 mm hg vs 111.8±8.6 mm hg, р=0.000), daily pulse BP 50.2±4.8 mm hg vs 44.2±7.6 mm hg, p=0.000), daily mean brachial artery stiffness index - ASI (161.9±28.3 mm hg vs 142.2±24.5 mm p=0.000), carotid-femoral pulse wave velocity (11.6±2.5 m/s vs 10.5±2.3 m/s, p=0.029). In single-factor logistic regression models all these measures were shown to have predictive value in AHT escape phenomena development. According to multifactor logistic regression analysis that included carotid-femoral pulse wave velocity more than 10.8 m/s, daily mean ASI&gt;137, daily SBP&gt;124 mm hg, and daily pulse BP&gt;46 mm hg, the only independent predictor on the background of effective AHT at the beginning of the observation was daily SBP&gt;124 mm hg (odds ratio 19.1, 95% confidence interval 3.6-101.8; p=0.0004). Conclusion. BP level and artery stiffness index measured on the background of effective AHT at the beginning of the observation are predictors for escape phenomena development and can be used for effectiveness and required frequency of therapy management prognosis.

Effect of omeprazole on antihypertensive efficacy of amlodipine in patients with comorbid pathology – arterial hypertension and acid-dependent disease

Objective:The problem of drug interactions is increasingly important today because they may induce serious adverse events as well as interfere with efficacy of pharmacotherapy. Combinations of drugs are most often prescribed to patients presenting with comorbid pathology. The incidence of a combination of arterial hypertension (AH) and acid-dependent diseases (ADDs) varies widely ranging from 11.6 to 50%. One of combinations of drugs prescribed to such patients is a combination of calcium channel blocker amlodipine and proton pump inhibitor omeprazole. The latter in the human body undergoes biotransformation mediated at the level of cytochrome P450 by isoenzymes CYP2C19 and CYP3A4. Amlodipine is a substrate of the isoenzyme CYP3A4, which increases the probability of the development of interaction between these drugs. The purpose of our study was to investigate antihypertensive efficacy of amlodipine in patients suffering from arterial hypertension combined with acid-dependent diseases and additionally taking omeprazole.Method:Study included a total of 150 patients with AH and ADD. Antihypertensive therapy was evaluated by means of office measuring of arterial pressure (AP) and circadian monitoring of AP (CMAP). The followed-up patients with AH and ADD were divided into 2 groups. Group One was composed of hypertensive patients undergoing pharmacotherapy with 10 mg amlodipine, whose condition required due to exacerbation of ADD administration of omeprazole at a dose of 20 mg for a period from 3 to 4 weeks. Group Two comprised hypertensive patients receiving antihypertensive therapy consisting of 10 mg amlodipine, who were found to have remission of acid-dependent diseases, with no additional medication taken.Results:The obtained findings demonstrated that one of the commonly used drug combinations in treatment of patients with AH and ADD in ambulatory conditions was a combination of omeprazole and amlodipine, accounting for 7.1%. The results of office measurement of arterial pressure (AP) 2 weeks after initiating pharmacotherapy with omeprazole in patients with AH and ADD demonstrated that the patients receiving omeprazole in addition to antihypertensive therapy were found to have a statistically significant decrease in systolic arterial pressure (SAP) and statistically significantly more pronounced dynamics of a decrease in diastolic arterial pressure (SAP) (p<0.05) compared with those not receiving therapy with omeprazole. Also, in the group of patients taking omeprazole, the findings of circadian monitoring of blood pressure (CMAP) showed a statistically significant decrease in average circadian SAP, average circadian DAP, mean value of daytime SAP and mean value of nighttime SAP (p<0.05).Conclusion:The obtained findings demonstrated that simultaneous prescription of amlodipine and omeprazole to patients with concomitant pathology, i.e., AH and ADD, turned out to enhance the antihypertensive affect of amlodipine, which probably resulted from substrate competition of amlodipine and omeprazole at the level isoenzyme CYP 3A4 of cytochrome P450.

HYPERTENSION AND DIABETES MELLITUS TYPE 2

Aim. To study the effect of long-term combined antihypertensive therapy with lisinopril plus amlodipine on the parameters of central aortic pressure (CAD) and visceral obesity in patients with arterial hypertension (HT) combined with type 2 diabetes mellitus (DM). Material and methods. 30 patients with stage III of HT and DM type 2 aged 40-65 years were included into the study. After "washout period", combined therapy with amlodipine 6.2Ѓ}2.5 mg/day and lisinopril 12.3Ѓ}5.0 mg/day was prescribed, hypolipidemic therapy with atorvastatin 17.0Ѓ}4.7 mg/day and combined hypoglycemic therapy with metformin 1093.8Ѓ}253.6 mg/day and gliclazide 82.1Ѓ}38.5 mg/day were continued within 24 weeks. Initially, and after 24 weeks, a standard physical examination, 24-hour CAP parameters monitoring, body composition analysis with a percentage of visceral fat calculation, a visceral fat index (VAI) determination, the degree of adipose tissue dysfunction and the level of glycated hemoglobin (HbA1c) assessment were performed. Results. Because of long-term therapy with lisinopril + amlodipine, a significant decrease in the level of office systolic (SBP) and diastolic blood pressure (DBP) by 22.3 and 12.5%, respectively, heart rate by 9,8%, and HbA1C level by 1.4% was found in comparison with the initial values. According to bioimpedanceometry a statistically significant decrease in the percentage of visceral fat (by 13.6%) was revealed, as well as VAI (by 22.5%) and the percentage of patients with very high visceral fat (Δ%=-36.7, р&lt;0.05). Indicators of central hemodynamics were significantly improved in the form of decrease in the average daily, daytime and nighttime values of aortic SBP, DBP, pulse blood pressure, and augmentation index. Conclusions. Thus, long-term combined therapy with lisinopril and amlodipine has shown not only high antihypertensive efficacy and the ability to reliably improve the parameters of CAD, but also to reduce the activity of visceral obesity, providing an additional positive metabolic effect without adjusting the dose of statins and hypoglycemic drugs.

EFFICACY EVALUATION OF THE TRANSITION TO FIXED COMBINATION DRUG PRESTANCE IN PATIENTS WITH INSUFFICIENT CONTROL OF BLOOD PRESSURE BY OTHER ANTIHYPERTENSIVE MEDICATIONS OR COMBINATIONS: REGIONAL PROGRAM OBJECTIVE

Aim.To evaluate efficacy of the fixed combination of perindopril arginine and amlodipine (original drug PRESTANCE, JSC “Servier”, France) in achievement of blood pressure (BP) control in patients non­controlled with other antihypertensive medications.Material and methods. In the study, in real world setting, 250 arterial hypertension (AH) outpatients were included. The levels of systolic (SBP) and diastolic (DBP) blood pressure were assessed and “vascular age”, at baseline, in 1 and 3 months (visit 2) of treatment with PRESTANCE.Results. In transition of patients to PRESTANCE there was decrease of SBP from 166,6±8,9 to 142,1±6,1 mmHg in 1 month (р&lt;0,001) and to 131,1±6,1 mmHg in 3 months. (р&lt;0,001), that is by 36 mmHg. BP decrease with the studied drug was similar in men and women, in patients older and younger 60. Target BP was reached in 79,6% of patients. The parameter “vascular age” after transition to PRESTANCE decreased in 3 months from 67,3±10,5 y. o. to 59,2±8,86 y. o., that is by 8,1 years.Conclusion.Transition from mono­ or combination therapy to fixed combination of perindopril arginine/amlodipine releases rapid and potent antihypertensive efficacy in patients not reached the target BP at any previous therapy, including combination of perindopril with amlodipine.

Dopamine‐β‐monooxygenase inhibitors obtained by structure based methods exhibited anti‐hypertensive effect in L‐NAME induced hypertensive rats

IntroductionHypertension is the leading cause of mortality worldwide (Kwan G.F. et. al., Circulation, 2016). While classical anti‐hypertensives like ACE inhibitors, ARBs, calcium channel blockers, beta blockers and diuretics are widely used, they have their own limitations and no new type of drugs emerged in the last few years that use body's own blood pressure lowering mechanism. Dopamine β‐monooxygenase (DBM), expressed in noradrenergic nerve terminals as well as in adrenal medullary chromaffin cells, which convert dopamine into norepinephrine, is a novel target whose inhibition has been shown to help the treatment of hypertension with several advantages over the classical antihypertensives. However, DBM inhibitors are few in number, often result in side‐effects and are frequently non‐responsive to specific population, probably since the known inhibitors so far have been designed on ligand based methods. We hypothesize that rational and three dimensional structure based identification of novel inhibitors may overcome such problems.ObjectiveTo identify novel inhibitors of DBM and evaluate their anti‐hypertensive properties in L‐NAME induced hypertensive rat model.Design and methodAn experimentally validated computational model for human DBM, built in our lab, was used for structure‐based, rational drug design. The three‐dimensional model was used for virtual screening against various small molecule databases. Identified top hits were then tested in vitro against DBM with known inhibitors nepicastat and disulfiram as controls. Binding of the inhibitors to DBM were validated using fluorescence and CD spectroscopy as well as ITC. Pharmacokinetic analysis was performed computationally. Cyto‐ and hemo‐toxicities of the lead compounds were assessed ex vivo. Finally. their antihypertensive efficacies were evaluated in L‐NAME induced hypertensive rat model.ResultsVirtual screening of various compound libraries revealed 69 hits which were then assessed in vitro using a repertoire of biochemical and biophysical methods. UDSC‐171, 180 and 142 were discovered to be potent inhibitors of DBM with IC50s of 1μM, 5.5μM and 18μM, respectively. The inhibitors displayed KD values against DBM in the range of 100nm to 1μM. In silico pharmacokinetic analysis indicated that the molecules are unable to cross the BBB. High doses (up to 50μM) of the lead compounds showed acceptable cellular tolerance against HEK293 cell line and insignificant hemo‐toxicities against RBCs. These three leads were successful in preventing elevated systolic blood pressure in L‐NAME induced hypertensive rat models.ConclusionsPresent study successfully developed rapid, systematic and non‐expensive biophysical, biochemical and computational tools for the identification, characterization and validation of DBM inhibitors. Moreover, UDSC‐171, 180 and 142 have been discovered and validated as novel antihypertensives against L‐NAME induced hypertensive rats. (Indian Patent filed for the present study with app. no. 201711036983)Support or Funding InformationDepartment of Biotechnology, Govt. of India