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https://www.readbyqxmd.com/read/28883863/the-evolution-of-natriuretic-peptide-augmentation-in-management-of-heart-failure-and-the-role-of-sacubitril-valsartan
#1
Srikanth Yandrapalli, Wilbert S Aronow, Pratik Mondal, David R Chabbott
Heart failure (HF) is one of the leading causes of morbidity, mortality, and health care expenditures in the US and worldwide. For three decades, the pillars of treatment of HF with reduced ejection fraction (HFrEF) were medications that targeted the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS). Prior attempts to augment the natriuretic peptide system (NPS) for the management of HF failed either due to lack of significant clinical benefit or due to the unacceptable side effect profile...
August 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28844335/sacubitril-valsartan-an-important-piece-in-the-therapeutic-puzzle-of-heart-failure
#2
REVIEW
Pedro Marques da Silva, Carlos Aguiar
Sacubitril/valsartan (LCZ696), a supramolecular sodium salt complex of the neprilysin inhibitor prodrug sacubitril and the angiotensin receptor blocker (ARB) valsartan, was recently approved in the EU and the USA for the treatment of chronic heart failure (HF) with reduced ejection fraction (HFrEF) (NYHA class II-IV). Inhibition of chronically activated neurohormonal pathways (the renin-angiotensin-aldosterone system [RAAS] and sympathetic nervous system [SNS]) is central to the treatment of chronic HFrEF. Furthermore, enhancement of the natriuretic peptide (NP) system, with favorable cardiovascular (CV) and renal effects in HF, is a desirable therapeutic goal to complement RAAS and SNS blockade...
August 23, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28805977/prevention-against-renal-damage-in-rats-with-subtotal-nephrectomy-by-sacubitril-valsartan-lcz696-a-dual-acting-angiotensin-receptor-neprilysin-inhibitor
#3
Kentaro Ushijima, Hitoshi Ando, Yusuke Arakawa, Kenichi Aizawa, Chisato Suzuki, Ken Shimada, Shu-Ichi Tsuruoka, Akio Fujimura
Although patients with chronic kidney disease (CKD) are at increased risk for end-stage renal disease and cardiovascular events, adequate drug therapies for preventing the deterioration of these conditions are still not established. This study was undertaken to evaluate a preventive effect of an angiotensin receptor-neprilysin inhibitor sacubitril/valsartan (LCZ696), which is converted to sacubitril and valsartan in the body, against the progression of renal disease in rats with subtotal nephrectomy, an animal model of human CKD...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28793821/the-effects-of-lcz696-in-patients-with-hypertension-compared-with-angiotensin-receptor-blockers-a-meta-analysis-of-randomized-controlled-trials
#4
Yang Zhao, Heng Yu, Xu Zhao, Ruixin Ma, Ningyin Li, Jing Yu
LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, has been demonstrated to have greater advantages in the treatment of heart failure compared with angiotensin-converting enzyme inhibitors, enalapril, or angiotensin receptor blockers (ARBs). However, studies that compared the efficacy and safety of LCZ696 against valsartan in patients with hypertension are limited. To provide further evidence for the benefits of LCZ696 and to make this assessment, a meta-analysis of randomized controlled trials (RCTs) was performed...
September 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28769873/targeting-obesity-and-diabetes-to-treat-heart-failure-with-preserved-ejection-fraction
#5
REVIEW
Raffaele Altara, Mauro Giordano, Einar S Nordén, Alessandro Cataliotti, Mazen Kurdi, Saeed N Bajestani, George W Booz
Heart failure with preserved ejection fraction (HFpEF) is a major unmet medical need that is characterized by the presence of multiple cardiovascular and non-cardiovascular comorbidities. Foremost among these comorbidities are obesity and diabetes, which are not only risk factors for the development of HFpEF, but worsen symptoms and outcome. Coronary microvascular inflammation with endothelial dysfunction is a common denominator among HFpEF, obesity, and diabetes that likely explains at least in part the etiology of HFpEF and its synergistic relationship with obesity and diabetes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28737127/pharmacokinetics-and-safety-of-sacubitril-valsartan-lcz696-in-patients-with-mild-and-moderate-hepatic-impairment%C3%A2
#6
Kenneth M Kulmatycki, Thomas Langenickel, Wai Hong Ng, Parasar Pal, Wei Zhou, Tsu-Han Lin, Iris Rajman, Priyamvada Chandra, Gangadhar Sunkara
OBJECTIVES: To assess the protein binding and pharmacokinetics of sacubitril/valsartan analytes (sacubitril, sacubitrilat, and valsartan) in an open-label, single oral dose (200 mg), parallel-group study in patients with mild and moderate hepatic impairment (Child-Pugh class A and B) and matched healthy subjects. METHODS: This study enrolled 32 subjects (n = 8 in each hepatic impairment and matched healthy subjects groups). Blood samples were collected at pre-determined time points to assess pharmacokinetics of sacubitril, sacubitrilat, and valsartan...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28714615/-arni-new-abbreviation-for-a-new-class-of-treatment-of-heart-failure
#7
Soran Karimzadeh, Hazrije Mustafić, Tomoe Stampfli Andres
ARNI (Angiontensin Receptor Neprilysin Inhibitor) are a new class of drug : the angiotensin and neprilysin inhibitors. This combined effect allows an optimisation of the heart failure treatment by acting on both pathways of the renin-angiotensin-aldosterone and of the natriuretic peptides. LCZ696 is a combined molecule of valsartan and sacubitril and is currently the only one on the market. Its efficacy has been shown in a large randomised trial in 2014, and LCZ696 is now part of the last 2016 European Society of Cardiology guidelines for the management of heart failure...
March 1, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28676030/heart-failure-with-preserved-ejection-fraction-a-dilemma-in-treatment-options
#8
Taylor Bramblett, Mohamed Teleb, Aymen Albaghdadi, Harsh Agrawal, Debabrata Mukherjee
Heart failure with preserved ejection fraction (HFpEF) makes up half of diagnosed heart failure cases and has similar outcomes compared to heart failure with reduced ejection fraction (HFrEF) but a discrepancy in knowledge and approach to treatment. HFpEF is diagnosed using the following criteria: symptoms, preserved ejection fraction (greater than 50%), and evidence of abnormal left ventricular filling or relaxation, or diastolic distensibility or stiffness. Studies conducted to examine the efficacy of angiotensin receptor blockers (irbesartan and candesartan), thiazide diuretics (chlorthalidone), and angiotensin converting enzyme inhibitors (perindopril) in the treatment of HFpEF, showed moderate efficacy but no clear benefit...
July 3, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28662936/angiotensin-receptor-neprilysin-inhibition%C3%A2-in-heart-failure-with-preserved%C3%A2-ejection-fraction-rationale-and-design-of-the-paragon-hf-trial
#9
REVIEW
Scott D Solomon, Adel R Rizkala, Jianjian Gong, Wenyan Wang, Inder S Anand, Junbo Ge, Carolyn S P Lam, Aldo P Maggioni, Felipe Martinez, Milton Packer, Marc A Pfeffer, Burkert Pieske, Margaret M Redfield, Jean L Rouleau, Dirk J Van Veldhuisen, Faiez Zannad, Michael R Zile, Akshay S Desai, Victor C Shi, Martin P Lefkowitz, John J V McMurray
OBJECTIVES: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF). BACKGROUND: HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes...
July 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28623750/lcz696-improves-cardiac-function-via-alleviating-drp1-mediated-mitochondrial-dysfunction-in-mice-with-doxorubicin-induced-dilated-cardiomyopathy
#10
Yan Xia, Zhangwei Chen, Ao Chen, Mingqiang Fu, Zhen Dong, Kai Hu, Xiangdong Yang, Yunzeng Zou, Aijun Sun, Juying Qian, Junbo Ge
AIMS: LCZ696, a novel angiotensin receptor neprilysin inhibitor, is effective in treating heart failure patients. Doxorubicin (DOX) is an effective antitumor medication but the cardiotoxicity limited its clinical use. In this study, we aimed to determine the effect of LCZ696 on DOX-induced cardiomyopathy in mice and in vitro and to explore related mechanisms focusing on fission protein dynamin-related protein 1 (Drp1). METHODS AND RESULTS: In human study, we found that myocardial fission protein Drp1 expression and its ser 616 phosphorylation were significantly increased in dilated cardiomyopathy (DCM) patients...
July 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28614052/safety-of-the-neprilysin-renin-angiotensin-system-inhibitor-lcz696
#11
REVIEW
Bo Li, Yunhe Zhao, Bo Yin, Mengfei Helian, Xinmei Wang, Feng Chen, Hongxia Zhang, Hui Sun, Bin Meng, Fengshuang An
OBJECTIVES: The combined neprilysin/rennin-angiotensin system inhibitor sacubitril/valsartan (LCZ696) has shown its superiority over ACEI/ARB therapy. In view of the existing concern of its adverse effects, we aimed to provide evidence of the safety of the new drug. RESULTS: A total of 6 randomized trials with 11,821 subjects were included in this analysis. No significant differences were found in any adverse effects between LCZ696 and ACEI/ARB or placebo groups...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28599060/evaluation-of-pharmacokinetic-and-pharmacodynamic-drug-drug-interaction-of-sacubitril-valsartan-lcz696-and-sildenafil-in-patients-with-mild-to-moderate-hypertension
#12
Hsiu-Ling Hsiao, Thomas H Langenickel, Jesika Petruck, Kiran Kode, Surya Ayalasomayajula, Uwe Schuehly, Michael Greeley, Parasar Pal, Wei Zhou, Margaret F Prescott, Gangadhar Sunkara, Iris Rajman
Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cGMP, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, 3-period, single sequence study, patients with mild-to-moderate hypertension (153.8±8.2 mm Hg mean SBP) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil co-administration...
June 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28569442/first-derivative-emission-spectrofluorimetric-method-for-the-determination-of-lcz696-a-newly-approved-fda-supramolecular-complex-of-valsartan-and-sacubitril-in-tablets
#13
Marwa A A Ragab, Shereen M Galal, Mohamed A Korany, Aya R Ahmed
LCZ696 (sacubitril/valsartan, Entresto™) is a therapy lately approved by United States Food and Drug Administration (US FDA) as a heart failure therapy. It is claimed to decrease the mortality rate and hospitalization for patients with chronic heart failure. This study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions that may affect its fluorescence. Various conditions were studied, for example studying the effects of organized media, solvents and pH, which may affect the fluorescence behavior of sacubitril...
June 1, 2017: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#14
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
May 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28492561/-sacubitril-valsartan-a-new-and-effective-treatment-for-heart-failure-with-reduced-ejection-fraction
#15
Michele Senni, Bruno Trimarco, Michele Emdin, Luciano De Biase
Despite significant therapeutic advances, patients with chronic heart failure and reduced ejection fraction (HFrEF) remain at high risk for heart failure progression and death. The PARADIGM-HF study, the largest outcome trial in HFrEF, has shown improved cardiovascular outcomes with sacubitril/valsartan (Entresto®, Novartis), previously known as LCZ696, compared with angiotensin-converting enzyme (ACE) inhibitor therapy, possibly leading us to a new era for heart failure treatment. Sacubitril/valsartan represents a first-in-class drug acting through inhibition of angiotensin receptor and neprilysin, thus modulating the renin-angiotensin-aldosterone system and vasoactive substances such as natriuretic peptides...
January 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28419972/neprilysin-inhibitors-a-new-hope-to-halt-the-diabetic-cardiovascular-and-renal-complications
#16
REVIEW
Vajir Malek, Anil Bhanudas Gaikwad
Diabetes is an enormous and ever-growing calamity and a global public health threat of the 21st century. Besides insulin and oral hypoglycaemic drugs, blockage of the renin-angiotensin system (RAS) denotes a key pharmacotherapy for the management of cardiovascular (CVD) and chronic kidney diseases (CKD), which are the leading causes of disability and death among diabetic patients. Neprilysin (NEP) inhibition, auxiliary to RAS blockage increases the bioavailability of natriuretic peptides and benefits the cardio-renal system...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#17
REVIEW
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
April 17, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28413968/hypertension-and-heart-failure-with-preserved-ejection-fraction-connecting-the-dots
#18
Costas Tsioufis, Georgios Georgiopoulos, Dimitrios Oikonomou, Costas Thomopoulos, Niki Katsiki, Alexandros Kasiakogias, Christina Chrysochoou, Dimitrios Konstantinidis, Theodoros Kalos, Dimitrios Tousoulis
Heart failure (HF) with preserved ejection fraction (EF) (HFpEF) accounts for approximately 50% of HF cases and its prevalence relative to HF with reduced EF is rising. Hypertension (HT) is the most common co-morbidity in HFpEF patients and it is implicated in both the pathogenesis and the prognosis of the disease. Therefore, HT is a modifiable risk factor of high yield in HFpEF. We reviewed the literature for epidemiologic data supporting the co-aggregation of the two entities as well as patho-physiologic mechanisms linking HT to HFpEF...
April 14, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28398362/-the-relationship-between-natriuretic-peptides-and-neprilysin-pathways-the-clinical-simplification-against-the-complexity-of-biological-systems
#19
Giuseppe Di Tano, Aldo Clerico
A large body of evidence supports the use of natriuretic peptides (brain natriuretic peptide [BNP] and N-terminal proBNP [NT-proBNP]) for the evaluation and management of patients with heart failure over time. Elevated values reflect an enhanced counterregulatory response to hemodynamic stress and are indicative of heart failure severity, thus predicting prognosis. The clinical relevance and result interpretation of natriuretic peptides for monitoring therapy are still debated, and our understanding of their complex nature is still far from being complete...
February 2017: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28378286/resetting-the-neurohormonal-balance-in-heart-failure-hf-the-relevance-of-the-natriuretic-peptide-np-system-to-the-clinical-management-of-patients-with-hf
#20
REVIEW
Speranza Rubattu, Filippos Triposkiadis
The natriuretic peptide (NP) system, which includes atrial natriuretic peptide, B-type natriuretic peptide, and C-type natriuretic peptide, has an important role in cardiovascular homeostasis, promoting a number of physiological effects including diuresis, vasodilation, and inhibition of the renin-angiotensin-aldosterone system. Heart failure (HF) is associated with defects in NP processing and synthesis, and there is a strong relationship between NP levels and disease state. NPs are useful biomarkers in HF, and their use in diagnosis and evaluation of prognosis is well established, particularly in patients with HF with reduced ejection fraction (HFrEF)...
May 2017: Heart Failure Reviews
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