angiotensin ii receptor blocker
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2022 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Tak Hon CHAN ◽  
Man Fung TSOI ◽  
Bernard Man Yung CHEUNG

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo Quagliariello ◽  
Simona Buccolo ◽  
Martina Iovine ◽  
Fabrizio Maurea ◽  
Domenica Rea ◽  
...  

Abstract Aims Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sacubitril–valsartan (LCZ 696) is a combination drug, made up of neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan, used for the treatment of heart failure in patients with a reduced ejection fraction. We hypothesized that LCZ 696, administered during doxorubicin, could improve cardiac function and cardiac inflammation in preclinical models. Methods Human Foetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of doxorubicin (200 nM) alone or in combination with LCZ-696 (100 mM) for 72 h. After the incubation period, we performed the following tests: cell viability, apoptosis and necrosis; expression of malondialdehyde and 4-hydroxynonenal and concentration of intracellular Ca2+. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of TLR4/MyD88; mTORC1 Fox01/3a; NF-κB). C57Bl/6 mice were untreated (Sham, n = 6) or treated for 10 days with doxorubicin i.p. at 2.17 mg/kg (DOXO, n = 6), LCZ-696 at 60 mg/kg (LCZ, n = 6) or doxorubicin combined to LCZ-696 (DOXO-LCZ, n = 6). Ejection fraction, radial and longitudinal strain were analysed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. Results LCZ-696 exerts cardioprotective effects, enhancing cell viability of 48–54.6% compared to only doxorubicin-treated cells (P < 0.001 for all); LCZ 696 decreased NLRP3, MyD88 and NF-kB expression in cardiac cells. In preclinical study, LCZ 696 improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88 and NF-kB in cardiac tissues was seen in DOXO-LCZ group compared to DOXO mice (P < 0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with LCZ-696 indicating anti-inflammatory properties. Conclusions LCZ-696 exerts direct beneficial effects in cardiomyocytes exposed to doxorubicin. In preclinical models, LCZ-696 reduced inflammation and cytokine expression involved in doxorubicin-mediated cardiotoxicity.


2021 ◽  
Vol 20 (7) ◽  
pp. 3078
Author(s):  
O. A. Osipova ◽  
E. V. Gosteva ◽  
O. N. Belousova ◽  
T. P. Golivets ◽  
J. Yu. Chefranova ◽  
...  

Aim. To compare the effect of angiotensin II receptor blocker therapy (azilsartan, telmisartan) on fibrosis and immune inflammation markers in hypertensive patients with chronic kidney disease (CKD) after ischemic stroke (IS).Material and methods. The study included 76 hypertensive patients aged 60-74 years (mean age, 66±5 years) with CKD after IS. Patients were randomly divided into following pharmacotherapy groups: 38 patients — telmisartan group; 36 patients — azilsartan group. The control group consisted of 20 hypertensive people (mean age, 63±2 years) without a history of CKD and IS. The levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were determined by enzyme-linked immunosorbent assay (ELISA Kit, USA). The levels of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), interferon γ (INF-γ), monocytic chemoattractant protein 1 (MCP-1) were assessed using Vector-Best kit (Russia).Results. Six-month azilsartan therapy led to a decrease in the levels of MMP-9 by 19,9% (p<0,01), TIMP-1 by 7,5% (p<0,05), IL-1β by 7,8%, TNF-α by 13,5%, INF-γ by 7,1%, MCP-1 by 13% (p<0,05). Telmisartan therapy was associated with a decrease in the levels of MMP-9 by 39,1% (p<0,01), TIMP-1 by 16,4%, IL-1β by 10,1% (p<0,05), TNF-α by 20,8% (p<0,01), INF-γ by 14,6% (p<0,05), MCP-1 by 21,3% (p<0,01). Intergroup comparison revealed more pronounced changes in the levels of MMP-9 by 19,2% (p<0,01), TIMP-1 by 7,2% (p<0,05), TNF-α by 7,3% (p<0,05), INF-γ by 7,5% (p<0,05), and MCP-1 by 8,3% (p<0,05) when using telmisartan compared to azilsartan. When using telmisartan, the increase in glomerular filtration rate (GFR) was 14,2% (p<0,05) higher compared to azilsartan.Conclusion. Six-month telmisartan therapy in hypertensive patients with CKD after stroke was accompanied by a more pronounced decrease in markers of myocardial fibrosis (MMP-9, TIMP-1) and immune inflammation (TNF-α, INF-γ, MCP-1) compared with azilsartan, as well as with more pronounced improvement in renal function.


2021 ◽  
Vol 23 (6) ◽  
pp. 791-799
Author(s):  
M. M. Dolzhenko ◽  
S. A. Bondarchuk

The aim of the work – to analyze the effectiveness of a fixed combination of amlodipine and angiotensin-converting enzyme (ACE) inhibitor (lisinopril) or angiotensin II receptor blocker (valsartan) in patients with coronary heart disease (CHD), post-infarction cardiosclerosis (PIC), arterial hypertension (AH) regarding the blood pressure (BP) control and impact on a composite endpoint. Materials and methods. General clinical examination of 108 patients with PIC and AH was done at the Cardiology Department of Shupyk National Healthcare University of Ukraine within 12 months. Patients were divided into two groups. The first group patients (n = 50) were assigned to receive a fixed combination of valsartan and amlodipine (160 mg and 5 mg, respectively), and the second group patients (n = 58) were treated with a fixed combination of lisinopril and amlodipine (10 mg and 5 mg, respectively). Patients were followed-up for 12 months, including general clinical examination, office BP measurements, 24-hour BP monitoring, echodopplerography, monitoring of the composite endpoint. Exclusion criteria were hemodynamically significant heart valve lesions, permanent or temporary cardiac pacing, acute heart failure and implanted cardioverter-defibrillator, permanent form of atrial fibrillation, acute cerebrovascular disorder, decompensation of severe somatic pathology. Statistical analysis of the data obtained was performed using Microsoft Excel, IBM SPSS Statistics v. 23. Descriptive data were presented as arithmetic mean ± standard deviation (M ± SD) in the case of normal distribution of variables, data with distribution other than normal were presented in Me format (Q25; Q75), where Me was the median, Q25, Q75 – lower and upper quartiles (Q25; Q75), or as a percentage for categorical values with Pearson’s Chi-square (χ2) calculation. Differences in mean values were considered statistically significant at a level of Р < 0.05. Results. According to all statistical criteria, BP indicators did not differ in both patient groups. Systolic office BP in the first group was 133.00 (123.00; 140.25) mm Hg., in the second group – 130.00 (122.00; 140.00) mm Hg. In the first group, diastolic office BP was 81.00 (79.50; 81.00) mm Hg and in the second group – 80.00 (75.00; 86.00) mm Hg. No statistically significant differen­ces were found in the study groups when assessing mean BP levels during the 24-hour monitoring. In the assessment of index values, systolic BP load was higher than normal in 58 % of patients in the first group and in 56.9 % of patients in the second group (χ2 = 0.01; P = 0.53). The assessment of diastolic BP load indices revealed increased diastolic BP index in 72 % of patient in the first group and in 75.9 % – in the second group (χ2 = 0.2; P = 0.4). The number of patients with BP higher or less than 130/80 mm Hg was compared. Systolic BP was above and below 130 mm Hg in 56 % and 44 %, respectively, of the first group patients; the distribution was 37.9 % and 62.1 % in the second group. Therefore, the percentage of patients with target systolic BP was higher in the second group (χ2 = 3.52; P = 0.046). Analyzing the composite endpoint, a statistically significant difference in the Kaplan–Meier curves via the statistical criterion using a log-rank test (P = 0.007) was detected. Conclusions. No statistically significant differences were found in the analysis of office blood pressure and 24-hour blood pressure monitoring between amlodipine with lisinopril and amlodipine with valsartan groups. The detailed analysis revealed a greater percentage of patients with target blood pressure below 130/80 mm Hg among those under 65 years of age receiving amlodipine with lisinopril (χ2 = 3.52; P = 0.046). The better prognostic value of the fixed combination of amlodipine with lisinopril compared to the combination of amlodipine with valsartan (P = 0.007) was demonstrated by the endpoint analysis.


2021 ◽  
Vol 18 (3) ◽  
pp. 130-139
Author(s):  
Nikita B. Perepech ◽  
Irina E. Chazova ◽  
Juliya V. Zhernakova

Background. Obesity is an independent risk factor of the cardiovascular complications in patients with arterial hypertension (HTN). It can directly contribute to an increase in blood pressure (BP). Thus, the treatment of patients with HTN and obesity becomes a complex clinical problem, which requires new highly effective antihypertensive drugs. Aim. To assess the effectiveness and safety of novel angiotensin II receptor blocker azilsartan medoxomil (AZL-M) as monotherapy and in free combinations with diuretics and/or calcium antagonists in obese or overweight patients with HTN in real clinical practice. Materials and methods. An international multicenter observational non-interventional prospective study of the efficacy and safety of AZL-M in patients with hypertension and overweight or obesity was performed in the Russian Federation and the Republic of Kazakhstan. Patients took the drug for 6 months in accordance with the approved local instructions for use. All examinations were performed in accordance with routine clinical practice on the basis of a physicians decision. Results. In patients prescribed AZL-M as monotherapy (without dosage changes during the study) a significant decrease in systolic and diastolic blood pressure (systolic BP and diastolic BP, respectively) was observed (p0.001, compared to baseline); the average decrease in systolic BP and diastolic BP was 30.5012.67 and 14.478.65 mmHg, respectively (n=865). Target BP (140/90 mmHg or 140/85 mmHg in patients with diabetes mellitus) was achieved in 112 (94.12%), 547 (92.24%) and 135 (88.24%) of patients who were prescribed AZL-M at doses of 20, 40, or 80 mg/day, correspondingly. In patients receiving AZL-M in combination with a diuretic or calcium antagonist, the rate of achievement of ad blood pressure targets was 78.887.5% and 81.385.5%, respectively, and the frequency of response to therapy was 68.892.9% and 81.393.9%, respectively. During the entire observation period, 43 adverse events (AEs) were recorded, the most common of which were arterial hypotension (14 cases). All AEs associated with the study drug were of mild or moderate intensity. Conclusion. AEs administered as monotherapy and as part of combination therapy provided a statistically and clinically significant decrease in BP and a high frequency of target BP achievement in patients with HTN and metabolic disorders associated with overweight or obesity. Given the high efficacy and good tolerance of the drug, AEs can be considered as the drug of choice for the treatment of HTN in patients with overweight or obesity.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258684
Author(s):  
Sebastian Cremer ◽  
Lisa Pilgram ◽  
Alexander Berkowitsch ◽  
Melanie Stecher ◽  
Siegbert Rieg ◽  
...  

Aims Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. Methods and results We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59–0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43–0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. Conclusion These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1756
Author(s):  
Chen-Hung Lee ◽  
Kuo-Sheng Liu ◽  
Julien George Roth ◽  
Kuo-Chun Hung ◽  
Yen-Wei Liu ◽  
...  

Stent implantation impairs local endothelial function and may be associated with subsequent adverse cardiovascular events. Telmisartan, an angiotensin II receptor blocker that has unique peroxisome proliferator-activated-receptor-gamma-mediated effects on cardiovascular disease, has been shown to enhance endothelial function and limit neointimal hyperplasia. This study utilized hybrid biodegradable/stent nanofibers to facilitate sustained and local delivery of telmisartan to injured arterial vessels. Telmisartan and poly(d,l)-lactide-co-glycolide (PLGA) (75:25) were dissolved in hexafluoroisopropyl alcohol and electrospun into biodegradable nanofibrous tubes which were coated onto metal stents. By releasing 20% of the loaded telmisartan in 30 days, these hybrid biodegradable/stent telmisartan-loaded nanofibers increased the migration of endothelial progenitor cells in vitro, promoted endothelialization, and reduced intimal hyperplasia. As such, this work provides insights into the use of PLGA nanofibers for treating patients with an increased risk of stent restenosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Piret Lõiveke ◽  
Toomas Marandi ◽  
Tiia Ainla ◽  
Krista Fischer ◽  
Jaan Eha

Abstract Background Relatively high rates of adherence to myocardial infarction (MI) secondary prevention medications have been reported, but register-based, objective real-world data is scarce. We aimed to analyse adherence to guideline-recommended medications for secondary prevention of MI in 2017 to 2018 (period II) and compare the results with data from 2004 to 2005 (period I) in Estonia. Methods Study populations were formed based on data from the Estonian Health Insurance Fund’s database and on Estonian Myocardial Infarction Register. By linking to the Estonian Medical Prescription Centre database adherence to guideline-recommended medications for MI secondary prevention was assessed for 1 year follow-up period from the first hospitalization due to MI. Data was analysed using the defined daily dosages methodology. Results Total of 6694 and 6060 cases of MI were reported in periods I and II, respectively. At least one prescription during the follow up period was found for beta-blockers in 81.0% and 83.5% (p = 0.001), for angiotensin converting enzyme inhibitor/angiotensin II receptor blocker (ACEi/ARB) in 76.9% and 66.0% (p < 0.001), and for statins in 44.0% and 67.0% (p < 0.001) of patients in period I and II, respectively. P2Y12 inhibitors were used by 76.4% of patients in period II. The logistic regression analysis adjusted to gender and age revealed that some drugs and drug combinations were not allocated similarly in different age and gender groups. Conclusions In Estonia, adherence to MI secondary prevention guideline-recommended medications has improved. But as adherence is still not ideal more attention should be drawn to MI secondary prevention through systematic guideline implementation.


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