Antihypertensive Efficacy Research Articles

Efficacy and safety of dosage-escalation of low-dosage esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes and albuminuria: a single-arm, open-label study

The stimulation of mineralocorticoid receptors is linked to the development of hypertension and cardiovascular or renal damage in patients with diabetes, and the blockade of these receptors may be an effective treatment option. This open-label study with a 12-week treatment period assessed the antihypertensive (primary) and antialbuminuric (secondary) efficacy and safety of esaxerenone as an add-on therapy to a renin–angiotensin system inhibitor in hypertensive patients with type 2 diabetes and albuminuria (urinary albumin-creatinine ratio 30 to <1000 mg/g•Cr). Esaxerenone was administered over 12 weeks at a starting dosage of 1.25 mg/day, which was gradually titrated to 2.5 mg/day and 5 mg/day at weeks 4, 6, or 8 according to the dosage-escalation criteria based on serum K+ levels, the estimated glomerular filtration rate, and the likelihood/occurrence of hypotension. Of the 51 patients enrolled, 44 (86.3%) reached an esaxerenone dosage of 2.5 or 5 mg/day. The changes from the baseline in sitting systolic and diastolic blood pressures were −13.7 mmHg (p < 0.05) and −6.2 mmHg (p < 0.05), respectively. Significant decreases in blood pressure occurred regardless of age, baseline systolic blood pressure, glycated hemoglobin level, and estimated glomerular filtration rate. The urinary albumin-creatinine ratio decreased by 32.4% from the baseline (p < 0.05). Two consecutive serum K+ measurements ≥ 5.5 mEq/L occurred in one patient but resolved after dosage reduction. Esaxerenone showed antihypertensive and antialbuminuric effects and a low risk of hyperkalemia with dosage titration from 1.25 mg in Japanese hypertensive patients with type 2 diabetes and albuminuria receiving a renin–angiotensin system inhibitor.

Synthesis and Docking Study of Pyrimidine Derivatives Scaffold for Anti‐Hypertension Application

AbstractThe present work introduces four new macromolecules pyrrolo[2,3‐d]pyrimidine scaffolds substituted with various benzene‐sulfonamide moieties; those were picked up via cyclization of 2‐amino‐3‐cyanopyrroles with phenyl isothiocyanate. The newly prepared pyrrolopyrimidine derivatives have been elucidated by spectroscopic techniques (FT‐IR, 1HNMR, 13CNMR and MS) and elemental analyses. The antihypertensive activity of the synthesized pyrrolopyrimidine derivatives based on sulfonamide moiety was evaluated. All pyrrolopyrimidine derivatives were showed a potent antihypertensive activity than Prazosin that utilized as standard drug. The structure activity relationship (SAR) was studied to correlate the influence of sulfonamide group with the aminopyrimidine moiety. Molecular docking for the synthesized derivatives and theoretical statistics were carried out to expect their antihypertensive efficacy.

Efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in the acute treatment of moderate and severe hypertension: a randomized, double-blind, positive-drug parallel-controlled, multi-center clinical study

Objective: To evaluate the efficacy and safety of low dose sublingual nifedipine dripping pills (5 mg) in treating moderate and severe hypertension in comparison with normal dose (10 mg) of sublingual nifedipine dripping pills. Methods: This study was designed as a randomized, double-blind, positive drug parallel controlled, multi-center, non-inferiority clinical trial. Patients with moderate and severe hypertension were enrolled by 14 clinical trial centers, randomly divided into the trial group (sublingual 5 mg nifedipine dripping pills) and the control group (sublingual 10 mg nifedipine dripping pills). The changes in blood pressure were monitored continuously within 2 hours after the initial administration, repeated the dose in 20 minutes interval after the initial administration for up to additional 3 doses (maximum 4 doses) if the antihypertensive efficacy was not satisfactory. The efficacy of antihypertensive therapy between the two groups was evaluated by repeated administration rates and blood pressure changes at 60 minutes post the initial administration, and the safety of treatment was evaluated by recording adverse event rate of the two groups. Results: The anti-hypertensive effective rates at 60 minutes after sublingual administration were 83.5% (202/242) and 86.7% (208/240) respectively between the trial group and control group (χ(2)=1.307, P=0.253) . On the aspect of antihypertensive effectiveness at 60 minutes after single dose of sublingual administration, the anti-hypertension effective rates of the trial group and the control group were 85.6% (154/180) and 87.2% (164/188) respectively (χ(2)=0.221, P=0.639). Prevalence of the repeated administration was also similar between the two groups (25.6%(62/242) in the trial group and 21.7% (52/240) in the control group, χ(2)=1.043, P=0.307). On the safety aspect, there was no adverse events/reactions in the trial group, but there were 15 cases of adverse events/reactions occurred in control group (6.25%, χ(2)=15.611, P<0.001). Conclusions: In the treatment of moderate to severe hypertension, the antihypertensive efficacy of low dose nifedipine dripping pills is similar to that of conventional dosage, and the safety profile of low dose nifedipine dripping pills is better than that of the conventional dose.

Facilitating Production of Rice Dreg Peptides via Lactic Acid Bacterial Fermentation on Anti-Hypertension Efficacy

Facilitating Production of Rice Dreg Peptides via Lactic Acid Bacterial Fermentation on Anti-Hypertension Efficacy

Antihypertensive efficacy and safety of Vaccinium arctostaphylos berry extract in overweight/obese hypertensive patients: A randomized, double-blind and placebo-controlled clinical trial

ObjectivesTo evaluate the antihypertensive efficacy and safety of a standardized Vaccinium arctostaphylos (V. arctostaphylos) berry hydro-alcoholic extract in the overweight/obese hypertensive patients. DesignRandomized placebo-controlled trial. SettingBaqiyatallah hospital (Tehran, Iran). InterventionsThe antihypertensive efficacy and safety of 3-month intake of 400 mg extract capsule three times daily alongside standardized anti-hypertensive regimen in the treatment of 50 patients was compared with the placebo (n = 50). Main outcome measuresSBP (systolic blood pressure), DBP (diastolic blood pressure), body mass index, waist circumference, CBC (complete blood count), blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), BUN (blood urea nitrogen) and creatinine. ResultsSBP decreased from 152.1 ± 7.7 to 140.5 ± 10.7 in the V. arctostaphylos group and from 152.9 ± 8.1 to 150.8 ± 9.3 in the placebo group (P < 0.001). DBP decreased from 90.3±8 to 82.1±8.8 in the V. arctostaphylos group and from 89.6 ± 7.8 to 87.6 ± 7.9 in the placebo group (P < 0.001).The extract capsule had no significant effect on the other parameters (P > 0.05). Moreover, no drug side effect and adverse interaction with other antihypertensive drugs was observed in the patients. ConclusionsV. arctostaphylosberry extract improves blood pressure control and has safety and tolerability in the overweight/obese hypertensive patients taking standard antihypertensive drugs.

Association between Sympathetic Nervous System Activation, Obesity and Insulin Resistance

The review discusses the problem of overweight, obesity and metabolic syndrome and their activating effect on the sympathetic nervous system and the increase in blood pressure. Current epidemiological data on the prevalence of obesity and metabolic syndrome and trends in their occurrence in recent decades are presented, indicating the high significance of these disorders in modern health care and their important role in development of the overall disease burden. In accordance with the clinical guidelines, types of obesity are described with a special focus on its abdominal type, as a factor that increases cardiovascular risk. The mechanisms of sympathetic overactivity in obesity, including insulin resistance, hyperleptinemia, the effect of nonesterified fatty acids, obstructive sleep apnea and baroreflex impairment are considered in detail. In the second part of the paper experimental and clinical findings are presented indicating worsening of the hypertension mediated target-organ damage in the presence of concomitant obesity that emphases on the crucial role of amplified adrenergic stimuli in the formation of these disorders. The promoting effect of obesity and concomitant sympathetic nervous system overactivation on the development of left ventricular hypertrophy, endothelial dysfunction and vascular damage, renal dysfunction and cognitive decline are considered. Finally, body of evidence of high antihypertensive efficacy as well as prominent target organ protective features of the highly selective β 1 -blocker bisoprpolol are presented especially when it prescribed in patients with arterial hypertension and concomitant obesity and metabolic syndrome.

Possibilities of using Fosinopril, an angiotensinconverting enzyme inhibitor, combined with Diltiazem, a non-dihydropyridine calcium antagonist, as first-line therapy in the treatment of arterial hypertension (clinical case)

The article exemplified the successful experience of using combination therapy consisting of fosinopril, an angiotensin-converting enzyme inhibitor, and diltiazem, a non-dihydropyridine calcium antagonist, in a patient with a history of arterial hypertension, sinus tachycardia and bronchial asthma. The authors proved the high antihypertensive efficacy and safety of the therapy, its favourable effect on the daily profile of blood pressure and heart rate, and strong organ-protective properties, the ability to reduce the degree of left ventricular hypertrophy and microalbuminuria level.

Influence of subclinical hypothyroidism on indicators of 24-hour arterial blood pressure monitoring in hypertensive patients with high additional risk

Significant prevalence of arterial hypertension (40 % of the adult population) and unsatisfactory level of high blood pressure adequate control (only 14 % of the urban and 8 % of the rural population in Ukraine) underlines the need to study the factors influencing AH course and contributing to a lack of antihypertensive therapy efficacy. One of such factors is subclinical hypothyroidism (SH). Aim. To study Influence of subclinical hypothyroidism on indicators of 24-hour arterial blood pressure monitoring in hypertensive patients with high additional risk. Materials and methods. After signing of written informed consent for the study, 124 patients with arterial hypertension (AH) and 16 practically healthy people (control group) were involved. The main group included 32 AH patients (women 87.5 % (n = 28), men 12.5 % (n = 4)) with moderately elevated thyroid stimulating hormone level (TSH) (4.0–15.6 μD/ml) and normal levels of thyroid hormones. The comparison group consisted of 92 AH patients (women 81.52 % (n = 75), men 18.48 % (n = 17)) with normal levels of TSH (0.4–4.0 μD/ml). The groups of patients were matched for age (54.16 ± 10.16) years versus (57.69 ± 9.76) years, (P = 0.093), sex (P = 0.4319), height (P = 0.993), weight (P = 0.719), body surface area (P = 0.901), body mass index (P = 0.669). All patients underwent a combined 24-hour blood pressure monitoring and ECG using a “Cardiology-04-AD-3” device (St. Petersburg, RF). Results. AH patients with or without concomitant SH were of comparable mean daytime and nighttime indices of SBP and DPB, indicators of SBP and DBP variability, PBP, indices for hypertension and hypotension, circadian indices, indices of percentage SBP and DBP increases, SBP and DBP load (with the exception of daytime SBP load). Patients with AH and SH, in contrast to AH patients without SH, tended to have 8.5 % (P < 0.05) higher indices of daytime SBP load, and 19.3 % (P < 0.05) lower daytime DBP hypotension index. Conclusions . AH patients with or without concomitant SH are comparable by the vast majority of ABPM indicators. However, in AH patients with concomitant SH, unlike those without SH, a larger daytime SBP load and a lower daytime DBP hypotension index were detected.

Sex Specific Differences in a Lipodystrophy‐induced Hypertension Mouse Model

Obesity rate is higher in women than in men and is more strongly associated with hypertension in extremely obese women. However, the relative contribution of the adipose tissue itself to blood pressure control and to anti‐hypertensive drug's efficacy is not completely understood and is often difficult to assess because of its inter‐ and intra‐variability within subject and within sex.In the present study, we used a lipodystrophy‐induced hypertension mouse model, adipose prorenin receptor (PRR) KO mice, to investigate sex differences in the relative contribution of adipose tissue to hypertension and to antihypertensive drug's efficacy. Autonomic nervous system inhibitors and AT1R blockers (ARBs) were used to investigate whether the elevation of blood pressure observed in adipose PRR KO male and female mice was driven by the same mechanism. The decrease of systolic blood pressure (SBP) induced by losartan, an AT1R blocker, was exacerbated in high fat (HF)‐fed adipose PRR KO female mice compared with control female mice but not in male mice (Delta SPB: CTL male, −7.9±1.5 mmHg; KO male, − 6.4±3.1 mmHg; CTL female, −5.3±1.9 mmHg; KO female, −14.2±0.9 mmHg). In contrast, the contribution of the autonomic nervous system, assessed via injections of propranolol, atropine and chlorisondamine, revealed that the tachychardic response was significantly greater in HF‐fed adipose PRR‐KO male mice compared with control, but not in female mice (Delta heart rate: CTL male, +114.2±12.1 bpm; KO male, +156.0±11.1 bpm; CTL female, +84.8±10.1 bpm; KO female, +89.8±21.3 bpm). Together, our data indicated that SBP elevation was primarily mediated by an AngII‐dependent mechanism in HF‐fed adipose PRR‐KO female mice whereas it was mainly driven by the para‐sympathetic nervous system in HF‐fed male adipose PRR‐KO mice. The present study also suggested that the presence of an expanded adipose tissue decreased the ability of female to respond to ARBs whereas it decreased the ability of male to respond to autonomic nervous system inhibitors. Interestingly, plasma sPRR, the soluble form of PRR, is higher in female than in obese male mice (CTL: Male: 2.8 ± 0.3 ng/ml; Female: 5.1 ± 0.5 ng/ml) and in HF‐fed adipose PRR KO female than in adipose PRR KO male mice (KO: Male: 7.1 ± 0.1 ng/ml; Female: 11.6 ± 2.4 ng/ml). Whether sPRR contributes to obesity‐hypertension and to the phenotype observed in adipose PRR‐KO mice through a sex specific mechanism is currently under investigation. Together our data support the importance of personalized medicine for antihypertensive treatment choices.Support or Funding InformationNational Institutes of Health Grants (R01‐HL‐130463), American Heart Association (13SDG17230008), National Institute of General Medical Sciences (P20‐GM103527), University of Kentucky, Center for Clinical and Translational Sciences (UL1TR000117)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

RETRACTED ARTICLE: Vasodilatory Properties of Sacubitril/Valsartan Explored in Hypertensives Aged Over 55Years: A Meta-Analysis.

A complete assessment of the efficacy and safety of sacubitril/valsartan for hypertension is not available yet. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) by incorporating only RCTs including patients aged > 55 years in which the antihypertensive efficacy and safety of sacubitril/valsartan were compared with those of a reference drug (comparator). The mean reductions in systolic blood pressure and diastolic blood pressure in the sitting position (msSBP and msDBP, respectively)were assumed as primary efficacy endpoints. Even mean reduction in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure(maDBP), were explored. Adverse events (AEs) were taken as safety outcomes. Five RCTs were included for a total of 1513 patients for analysis. In all studies, the comparator drug was an ARB (valsartan in two cases and olmesartan in the remaining three cases). Compared with ARBs, after 12 weeks there was a significant reduction in msSBP (weight mean difference [WMD] = - 5.41 mmHg, 95% CI - 7.0 to - 3.8; P < 0.01), msDBP (WMD = - 1.22 mmHg, 95% CI : - 2.15 to - 0.3; P < 0.01), maSBP (WMD = - 4.58 mmHg, 95% CI: - 5.62 to - 3.54; P < 0.01) and maDBP (WMD = - 2.17mm Hg, 95% Cl: - 2.78 to - 1.56; P < 0.01). Comparison with ARBs consistently showed superiority of the antihypertensive effect of sacubitril/valsartan. Therefore, based on the preliminary evidence derived from these small trials, sacubitril/valsartan could be proposed as an elective drug for hypertension in patients aged over 55.

Searching for calcium antagonists for hypertension disease therapy from Moutan Cortex, using bioactivity integrated UHPLC-QTOF-MS.

Calcium channel blockers (CCBs) are currently the most commonly used drugs for the treatment of hypertension. Moutan Cortex (MC), a traditional Chinese herb, has been found to have an anti-hypertensive effect. However, its potential mechanisms in the regulation of intracellular calcium concentration ([Ca2+ ]i ) remain poorly understood. The main objective of this work was to identify the potential calcium antagonists from MC and study their molecular mechanisms. Ultra-high performance liquid chromatography-quadrupole-time-of-fight-mass spectrometry (UHPLC-QTOF-MS) analysis combined with a dual-luciferase reporter assay was utilised to systematically screen the calcium antagonistic active ingredients in the methanol extract of MC. Additionally, the molecular mechanism of these compounds was further studied using live-cell imaging analysis with the calcium ion (Ca2+ ) probe dye fluo-4/AM to monitor changes in [Ca2+ ]i . Three monoterpenoids (paeoniflorin, benzoylpaeoniflorin and mudanpioside C), one phenolic acid (paeonol) and one gallotannin (1,2,3,4,6-O-pentagalloylglucose) were screened out as potential calcium antagonists in MC. Among them, the calcium antagonistic activity of benzoylpaeoniflorin, mudanpioside C and 1,2,3,4,6-O-pentagalloylglucose is first reported. Additionally, paeoniflorin, benzoylpaeoniflorin, mudanpioside C and paeonol can effectively block voltage-operated Ca2+ channels (VOCCs) to exert calcium antagonism, while 1,2,3,4,6-O-pentagalloylglucose plays a role in blocking inositol 1,4,5-trisphosphate receptors (IP3Rs). This work indicated that the anti-hypertensive efficacy of MC acted through multiple components selectively antagonising multiple cell signalling pathways to regulate [Ca2+ ]i . Furthermore, they could be considered as a reference standard for controlling the quality of Chinese medicinal materials.

The Antihypertensive Efficacy and Safety of Catheter-Based Renal Denervation: A Report of 2 Cases

The patient was a 49-year-old male. The patient was admitted to the hospital because he had suffered recurring dizziness and headache for more than 10 years and aggravated symptoms for 3 days.

Improving the cognitive functions in the middle-aged patients with essential arterial hypertension after the treatment with amlodipine/valsartan single-pill combination

Different antihypertensive drugs differently affect cognitive function, and data on the effect of single-pill combination (SPC) of antihypertensive drugs on cognitive function are presented only in single studies.Aim. To investigate the impact of amlodipine/valsartan SPC (A/V SPC) on blood pressure (BP) level and cognitive functions in the middle-aged antihypertensive treatment-naive patients with stage II grade 1-2 essential arterial hypertension.Methods. A group of patients with stage II grade 1-2 essential arterial hypertension who had not previously received regular antihypertensive treatment (n=38, age 49.7±7.0 years) was retrospectively formed. All the patients were treated with A/V SPC and all of them achieved target office BP (less than 140/90 mm Hg). And after 12-week follow-up (since the time of reaching the target BP) the antihypertensive treatment efficacy assessment using ambulatory BP monitoring (ABPM) were performed in all included hypertensive patients. Age-matched healthy people with normal BP (n=20, mean age 45.4±5.1years) represented a control group. In all participants cognitive functions were evaluated by 5 different tests at baseline and at the end of follow-up: Montreal Cognitive Assessment (MoCA); Trail Making test (part A and part B), Stroop Color and Word Test; verbal fluency test; 10-item word list learning task. Baseline Hamilton depression and anxiety rating scale data were also available in all individuals.Results. According to the ABPM data 24-hour, day-time and night-time systolic, diastolic and pulse BP significantly decreased after the treatment with A/V SPC (p&lt;0.001 for systolic and diastolic BP and p&lt;0.01 for pulse BP). After the treatment with A/V SPC significantly improved results of cognitive tests in hypertensive patients: decreased time in Trail Making Test part B (from 114.7±37.0 to 96.3±26.5 s; р=0.001); time difference between part B and part A of Trail Making Test (from 75.2±32.8 to 57.7±20.1 s; р=0.002); time in Stroop test part 3 (from 117.0±28.1 to 108.0±28.4 s; р=0.013); and interference score (from 50.9±19.2 to 43.1±22.0 s; р=0.011); increased MoCA score (from 28.4±1.3 to 29.4±1.2; р=0.001); as well as increased the 10-item word list learning task – immediate recall (from 5.7±1.3 to 6.5±1.2 words; р=0.001); 10-item word list learning task – delayed recall (from 6.3±2.1 to 6.9±1.7 words; р=0.006); literal fluency (from 11.7±3.4 to 13.2±3.2 words; р=0.020) and categorical fluency (from 7.3±2.5 to 9.5±2.9 words; p&lt;0.001). In control group at the end of follow-up compared to baseline significantly increased the 10-item word list learning task – immediate recall (from 5.8±0.9 to 6.6±1.1 words; р&lt;0.05) and delayed recall (from 5.9±1.8 to 8.2±1.4 words; р&lt;0.001).Conclusion. In retrospective analysis improvement of cognitive function was found in middle-aged patients with hypertension, taking A/V SPC for 12 weeks after reaching the target BP.

Efficacy of Sacubitril/Valsartan in Hypertension.

Sacubitril/valsartan (LCZ696) has progressed to be one of the most promising medication since its approval for chronic heart failure with reduced ejection fraction. Recent data have suggested a superior blood pressure control with LCZ696. What is the antihypertensive efficacy and safety profile of sacubitril/valsartan? Randomized controlled trials (RCTs) comparing the efficacy and safety of LCZ696 against a placebo or angiotensin receptor blocker (ARB). RCTs were identified from a comprehensive search in PubMed, Embase, Cochrane library, and clinicaltrials.gov. We used a change in systolic and diastolic blood pressures, both sitting as well as ambulatory, to calculate relevant effect sizes with their standard errors from the available change in mean and SD data. In addition, we also collected categorical data for the reported adverse effects from these trials. We performed a series of pairwise meta-analyses between LCZ696 versus an active comparator or a placebo. Eleven RCTs with a total of 6028 participants had the relevant data available. Our meta-analysis showed that LCZ696 is an effective and a safe treatment for hypertension. It outperformed ARBs in every category, and the results are consistent across the different dosages of LCZ696. Compared with ARBs, 200 mg of LCZ696 reduced systolic blood pressure and diastolic blood pressure (DBP) by 4.62 mm Hg (95% confidence interval, 3.33-5.90, P < 0.001) and 2.13 mm Hg (95% confidence interval, 1.69-2.57, P < 0.001), respectively. Similarly, 400 mg of LCZ696 reduced systolic blood pressure and diastolic blood pressure by 5.50 mm Hg (2.94-8.07, P < 0.001) and 2.51 mm Hg (1.80-3.21, P < 0.001), respectively, in comparison with ARBs. The adverse effects with LCZ696 were not significantly higher compared with ARBs or placebo. Sacubitril/valsartan is more effective for the management of hypertensive patients, compared with an ARB. Long-term prospective studies are required to identify whether this result translates into morbidity and mortality benefits.

Antihypertensive Efficacy of Fixed Combination of Amlodipine and Ramipril in Patients with Arterial Hypertension and Very High Cardiovascular Risk

Aim. To evaluate the antihypertensive efficacy and tolerability of a fixed combination of amlodipine and ramipril in hypertensive patients with very high cardiovascular risk. Material and methods. A retrospective cohort study of real clinical practice of prescribing antihypertensive drugs according to 255 medical records of outpatient hypertensive patients with a history of acute coronary syndrome (ACS) and coronary artery stenting was performed in the first part. An open observational study was performed in the second part. 69 people older than 18 years with a history of ACS and coronary artery stenting, without reaching the target blood pressure (BP) level while using free combinations of antihypertensive drugs and with indications for a fixed combination of ramipril and amlodipine were included into the study. Analysis of self-monitoring of BP, office BP, daily BP monitoring (ABPM) and patients’ adherence to treatment (Morisky-Green test) initially, after 4 and after 12 weeks of taking the fixed combination of ramipril and amlodipine was performed to assess the clinical efficacy of the studied drug. Results. It was found that 42.0% of patients did not follow the recommendations for regular intake of antihypertensive drugs. So, hypertension of all patients regarded as false-refractory, which was the basis for the prescription of the fixed combination of ramipril and amlodipine in accordance with clinical guidelines for the diagnosis and treatment of hypertension. After 4 weeks of therapy, there was significant decrease in office BP with the achievement and preservation of the target level by the 12th week, normalization to the 12th week of day and night BP variability in 54.9% of patients. 78.0% of patients followed medical recommendations for regular administration of antihypertensive drugs, none of the patients had adverse events. Conclusion. The use of fixed combinations of drugs, in particular, amlodipine and ramipril as a part of multicomponent therapy in hypertensive patients with very high cardiovascular risk, led to the achievement of target BP by the 4th week of therapy and stable preservation of antihypertensive effect in 12 weeks of treatment as well as gradual normalization of day and night BP variability in more than half of patients. Fixed combination of ramipril and amlodipine allowed to improve adherence of patients to cardiovascular diseases.

Effectiveness of Chrono-Pharmacotherapy Depending on the Salt Sensitivity of Patients with Arterial Hypertension and Diabetes Mellitus Type 2

Aim. To study the effect of two regimens of combined antihypertensive therapy during the day on daily monitoring of arterial pressure, central aortic pressure, and arterial stiffness, depending on the salt sensitivity of hypertensive patients with diabetes mellitus type 2. Material and methods. 130 hypertensive patients with type 2 diabetes mellitus were included into the study. They were divided into 2 subgroups: salt-sensitive (group 1) and salt-resistant (group 2), and then randomized to subgroups A and B of ongoing therapy: in the morning ramipril and indapamide retard, bedtime – amlodipine (subgroup 1A and 2A); or in the morning amlodipine and indapamide retard, bedtime – ramipril (subgroup 1B and 2B). Initially and after 24 weeks of antihypertensive therapy, 24-hour blood pressure monitoring was performed, the indices of central aortic pressure and arterial stiffness were determined. Results. After 24 weeks, in all subgroups, there was a significant positive dynamics of the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices. In the subgroup 1В, it was registered a significant improvement in the majority of parameters of 24-hour blood pressure monitoring (decrease in 24-hours systolic BP by 24.4%, 24-hours diastolic BP by 22.1%; p&lt;0.05), central aortic pressure (decrease in aortal systolic BP by 15.9%, aortal diastolic BP by 20.8%; p&lt;0.05) and vascular wall stiffness parameters (decrease in pulse wave velocity by 13.8%; p&lt;0.05) in comparison with group 1A (decrease in 24-hours systolic BP by 17.5%, 24-hours diastolic BP by 14.6%, aortal systolic BP by 12.7%, aortal diastolic BP by 9.7%, pulse wave velocity by 9.2%; p&lt;0.05 in comparison with the group 1B). In the case of salt-resistant patients, there were comparable positive changes in the parameters of 24-hour blood pressure monitoring, central aortic pressure and arterial stiffness indices against the background of both dosing regimens during the day. Conclusion. In the study, it was demonstrated the more pronounced antihypertensive and vasoprotective efficacy of the combination of thiazide-like diuretic with calcium channel blocker in the morning and ACE inhibitor in bedtime compared to the alternative regimen of prescribed pharmacotherapy in salt-sensitive patients, and comparable efficacy of both regimens in salt-resistant hypertensive patients with diabetes mellitus type 2.

Anti-Hypertensive Effect of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials.

BackgroundFor elderly patients suffering from arterial hypertension, a complete assessment of the efficacy and safety of sacubitril/valsartan used as an anti-hypertensive agent is not available yet. Therefore, we decided to perform a meta-analysis of randomized controlled trials (RCTs) to explore some endpoints concerning anti-hypertensive efficacy as well as safety of sacubitril/valsartan in elderly hypertensive patients.MethodsPubMed and Scopus have been extensively investigated with the help of some key words until June 15, 2018. The meta-analysis incorporated exclusively RCTs in which the anti-hypertensive efficacy and safety of sacubitril/valsartan were compared with those of a reference drug (comparator) that could be an angiotensin-converting enzyme inhibitor (ACEi), an angiotensin receptor blocker (ARB), a calcium channel blocker (CCB) or a beta-blocker. Continuous ambulatory blood pressure monitoring was required as an inclusion criterion in the studies to be included in the meta-analysis. The mean reductions in systolic blood pressure and diastolic blood pressure in the sitting position (msSBP and msDBP, respectively), as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were taken as safety outcomes.ResultsFive RCTs were included with a total of 1,513 patients for analysis. In all studies, the comparator drug was an ARB (valsartan in two cases and olmesartan in the remaining three cases). Compared with ARBs, after 12 weeks there was a significant reduction in msSBP (weight mean difference (WMD) = - 5.41 mm Hg, 95% confidence interval (CI): -7.0 to -3.8; P < 0.01), msDBP (WMD = -1.22 mm Hg, 95% CI : -2.15 to -0.3; P < 0.01), maSBP (WMD = -4.58 mm Hg, 95% CI: -5.62 to -3.54; P < 0.01) and maDBP (WMD = -2.17 mm Hg, 95% CI: - 2.78 to -1.56; P < 0.01) in elderly hypertensive patients at 12 weeks.ConclusionsSacubitril/valsartan may reduce arterial pressure more efficaciously than ARBs in elderly hypertensive patients. These results have to be confirmed by further RCTs with a good methodological quality, possibly with a greater sample size.

Антигипертензивная эффективность и приверженность лечению фиксированной комбинацией препаратов у амбулаторных пациентов в возрасте 50–65 лет с неконтролируемой артериальной гипертензией

Антигипертензивная эффективность и приверженность лечению фиксированной комбинацией препаратов у амбулаторных пациентов в возрасте 50–65 лет с неконтролируемой артериальной гипертензией

Anti-hypertensive efficacy of amlodipine dosing during morning versus evening: A meta-analysis.

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.

Chronopharmacology: Appraising the Influence of Biorhythms on the Efficacy and Safety of Antihypertensive Drugs.

This review is dedicated to chronopharmacology and chronotherapeutics of hypertension interventions. The aim of chronopharmacology is to determine the most suitable time for administration of a drug to enhance efficacy and safety, prevent tolerance, and minimize the untoward effects of the given therapy. In other words, chronotherapeutics and chronopharmacology optimize drug therapy through matching the disease rhythms to drug availability. Chronobiological principles to optimize the therapeutic effects of antihypertensive drugs attained significance a few decades ago. Circadian rhythm plays a pivotal role in the regulation of blood pressure and expresses as a contender for application of chronotherapeutics. Changes in the normal circadian rhythmic pattern of blood pressure also foretell the risk for developing cardiovascular events. This review highlights studies conducted on the chronopharmacology of different antihypertensive drug classes and prospective areas of chronotherapy to make it comprehensible for application in clinical practice to achieve optimum control of hypertension.