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LCZ696

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https://www.readbyqxmd.com/read/29776559/angioedema-in-heart-failure-patients-treated-with-sacubitril-valsartan-lcz696-or-enalapril-in-the-paradigm-hf-study
#1
Victor Shi, Michele Senni, Hendrik Streefkerk, Vikas Modgill, Wenchun Zhou, Allen Kaplan
BACKGROUND: PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. METHODS: Following sequential enalapril and sacubitril/valsartan run-ins, patients were randomized to twice-daily sacubitril/valsartan 200 mg or enalapril 10 mg...
August 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29718530/effect-of-lcz696-a-dual-angiotensin-receptor-neprilysin-inhibitor-on-isoproterenol-induced-cardiac-hypertrophy-fibrosis-and-hemodynamic-change-in-rats
#2
Toru Miyoshi, Kazufumi Nakamura, Daiji Miura, Masashi Yoshida, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Hiroshi Ito
BACKGROUND: Recent clinical studies have shown that treatment with LCZ696, a complex containing the angiotensin receptor blocker valsartan and neprilysin inhibitor sacubitril, improves the prognosis of heart failure patients with a reduced ejection fraction. This study evaluated whether LCZ696 affects left ventricular hypertrophy, fibrosis, and hemodynamics in isoproterenol (ISO)-treated rats compared with valsartan alone. METHODS: Male Wistar rats received subcutaneous saline (n = 10), subcutaneous ISO (2...
May 2, 2018: Cardiology Journal
https://www.readbyqxmd.com/read/29653073/a-zebrafish-heart-failure-model-for-assessing-therapeutic-agents
#3
Xiao-Yu Zhu, Si-Qi Wu, Sheng-Ya Guo, Hua Yang, Bo Xia, Ping Li, Chun-Qi Li
Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection...
March 20, 2018: Zebrafish
https://www.readbyqxmd.com/read/29608651/high-performance-thin-layer-and-high-performance-liquid-chromatography-coupled-with-photodiode-array-and-fluorescence-detectors-for-analysis-of-valsartan-and-sacubitril-in-their-supramolecular-complex-with-quantitation-of-sacubitril-related-substance-in-raw
#4
Marwa A A Ragab, Shereen M Galal, Mohamed A Korany, Aya R Ahmed
Valsartan (VAL) and sacubitril (SAC) are combined in a supramolecular complex, LCZ696, which is a newly approved remedy for heart failure. SAC-related substance (biphenyl methyl pyrrolidinone [BMP]) which also appears as an intermediate during SAC synthesis is considered to be a suspected impurity for SAC and/or LCZ696 tablets. The study investigates the analysis of VAL and SAC in their supramolecular complex along with SAC-related substance, BMP, using high performance thin-layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) with two different detectors; fluorescence detector (FLD) and diode array detector (DAD)...
March 28, 2018: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/29544929/angiotensin-receptor-neprilysin-inhibition-provides-superior-cardioprotection-compared-to-angiotensin-converting-enzyme-inhibition-after-experimental-myocardial-infarction
#5
Andrew R Kompa, Jiayu Lu, Thomas J Weller, Darren J Kelly, Henry Krum, Thomas G von Lueder, Bing H Wang
BACKGROUND: Angiotensin receptor neprilysin inhibitor (ARNi) enhances beneficial natriuretic peptides by inhibiting their breakdown through neprilysin. Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce. ARNi may be superior to ACEi in attenuating adverse cardiac remodeling and dysfunction post-myocardial infarction (MI)...
May 1, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29542073/combination-therapy-of-renin-angiotensin-system-inhibitors-and-%C3%AE-blockers-in-patients-with-heart-failure
#6
Kotaro Nochioka, Yasuhiko Sakata, Hiroaki Shimokawa
Renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system play crucial roles in heart failure with reduced ejection fraction (HFrEF). Clinical trials provide strong evidence of prognostic benefits for combination therapy with angiotensin-converting enzyme inhibitor (ACEI) and β-blocker in the treatment of HFrEF. Angiotensin receptor blocker (ARB) is not superior to ACEI in improving mortality and an alternative for patients who are intolerant to ACEI. Prognostic evidence for triple therapy which combined angiotensin receptor blocker (ARB) and ACEI in addition to β-blocker therapy, is still controversial in HFrEF...
March 15, 2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29532764/entresto-a-new-panacea-for-heart-failure
#7
Peter H Khalil, Ghazal Kabbach, Debabrata Mukherjee, Sarmad Said
Heart Failure (HF) is one of the main health care burdens in the United States and in the world. Many drugs are approved and used in practice for management of this condition; including beta blockers, diuretics, aldosterone antagonists, angiotensin converting enzyme inhibitors (ACEI's), and angiotensin receptor blockers (ARBs). Recently, the Food and Drug Administration (FDA) approved a drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection Fraction (HFrEF) patients instead of ACEI's and ARBs...
March 13, 2018: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29502102/combined-angiotensin-receptor-neprilysin-inhibitors-improve-cardiac-and-vascular-function-via-increased-no-bioavailability-in-heart-failure
#8
Rishi K Trivedi, David J Polhemus, Zhen Li, Daniel Yoo, Hiroshi Koiwaya, Amy Scarborough, Traci T Goodchild, David J Lefer
BACKGROUND: There is a paucity of data about the mechanisms by which sacubitril/valsartan (also known as LCZ696) improves outcomes in patients with heart failure. Specifically, the effects of sacubitril/valsartan on vascular function and NO bioavailability have not been investigated. We hypothesized that sacubitril/valsartan therapy increases circulating NO levels and improves vascular function in the setting of heart failure. METHODS AND RESULTS: Male spontaneously hypertensive rats underwent myocardial ischemia/reperfusion surgery to induce heart failure and were followed for up to 12 weeks with serial echocardiography...
March 3, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29500454/the-effects-of-angiotensin-receptor-neprilysin-inhibition-by-sacubitril-valsartan-on-adipose-tissue-transcriptome-and-protein-expression-in-obese-hypertensive-patients
#9
R Stinkens, B W van der Kolk, J Jordan, T Jax, S Engeli, T Heise, J W Jocken, M May, C Schindler, B Havekes, N Schaper, D Albrecht, S Kaiser, N Hartmann, M Letzkus, T H Langenickel, G H Goossens, E E Blaak
Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients...
March 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29374807/the-sacubitril-valsartan-a-first-in-class-angiotensin-receptor-neprilysin-inhibitor-arni-potential-uses-in-hypertension-heart-failure-and-beyond
#10
REVIEW
Kazuomi Kario
PURPOSE OF REVIEW: Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT1 ) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF)...
January 27, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29369824/was-the-enalapril-dose-too-low-in-the-paradigm-hf-trial
#11
Sabrina Bernardez-Pereira, Felix José Alvares Ramires, Rachel Figueiredo Tavares de Melo, Antonio Carlos Pereira-Barretto
Heart failure (HF) is a common clinical syndrome associated with significant morbidity and mortality, and there remains a clear need for innovative therapies that can modify disease progression. Sacubitril/valsartan (LCZ696) is a novel complex that combines simultaneous neprilysin inhibition and angiotensin II receptor blockade, that has demonstrated significant cardiovascular death or HF hospitalization reduction in the Prospective Comparison of Angiotensin Receptor/Neprilysin Inhibitor (ARNI) with Angiotensin-Converting Enzyme (ACE) Inhibitors to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial when compared to evidence-based doses of the gold-standard ACE inhibitor enalapril...
January 24, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#12
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29325796/lcz696-sacubitril-valsartan-an-angiotensin-receptor-neprilysin-inhibitor-attenuates-cardiac-hypertrophy-fibrosis-and-vasculopathy-in-a-rat-model-of-chronic-kidney-disease
#13
Yasunori Suematsu, Wanghui Jing, Ane Nunes, Moti L Kashyap, Mahyar Khazaeli, Nosratola D Vaziri, Hamid Moradi
BACKGROUND: Chronic kidney disease (CKD) is associated with cardiac hypertrophy, fibrosis, and increased risk of cardiovascular mortality. LCZ696 (sacubitril/valsartan) is a promising agent that has shown significant potential in treatment of heart failure. We hypothesized that LCZ696 is more effective than valsartan alone in the treatment of cardiovascular abnormalities associated with experimental CKD. METHODS AND RESULTS: Male Sprague-Dawley rats underwent 5/6 nephrectomy and were subsequently randomized to no treatment (CKD), 30 mg/kg valsartan (VAL), or 60 mg/kg LCZ696 (LCZ)...
April 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29296218/lcz696-a-promising-novel-agent-in-treating-hypertension-a-meta-analysis-of-randomized-controlled-trials
#14
Liwen Ye, Jian Wang, Qingwei Chen, Xixi Yang
Background: To determine the effectiveness and safety of LCZ696 for the clinical treatment of hypertension, we performed a meta-analysis of the previous clinical trials. Methods: Relevant English articles and randomized controlled trials were searched in Pubmed, Embase, EBSCO, Cochrane base and ClinicalTrials.gov. The last search date was July 20th, 2017. Results: Compared with 20mg olmesartan, 200mg and 400mg LCZ696 outperformed olmesartan in terms of reducing mean sitting systolic blood pressure, mean ambulatory systolic blood pressure, mean sitting diastolic blood pressure and mean ambulatory diastolic blood pressure...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29241885/cost-effectiveness-of-the-angiotensin-receptor-neprilysin-inhibitor-sacubitril-valsartan-for-patients-with-chronic-heart-failure-and-reduced-ejection-fraction-in-the-netherlands-a-country-adaptation-analysis-under-the-former-and-current-dutch-pharmacoeconomic
#15
COMPARATIVE STUDY
Isaac Corro Ramos, Matthijs M Versteegh, Rudolf A de Boer, Jolanda M A Koenders, Gerard C M Linssen, Joan G Meeder, Maureen P M H Rutten-van Mölken
OBJECTIVES: To describe the adaptation of a global health economic model to determine whether treatment with the angiotensin receptor neprilysin inhibitor LCZ696 is cost effective compared with the angiotensin-converting enzyme inhibitor enalapril in adult patients with chronic heart failure with reduced left ventricular ejection fraction in the Netherlands; and to explore the effect of performing the cost-effectiveness analyses according to the new pharmacoeconomic Dutch guidelines (updated during the submission process of LCZ696), which require a value-of-information analysis and the inclusion of indirect medical costs of life-years gained...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29180454/effect-of-sacubitril-valsartan-on-exercise-induced-lipid-metabolism-in-patients-with-obesity-and-hypertension
#16
RANDOMIZED CONTROLLED TRIAL
Stefan Engeli, Rudi Stinkens, Tim Heise, Marcus May, Gijs H Goossens, Ellen E Blaak, Bas Havekes, Thomas Jax, Diego Albrecht, Parasar Pal, Uwe Tegtbur, Sven Haufe, Thomas H Langenickel, Jens Jordan
Sacubitril/valsartan (LCZ696), a novel angiotensin receptor-neprilysin inhibitor, was recently approved for the treatment of heart failure with reduced ejection fraction. Neprilysin degrades several peptides that modulate lipid metabolism, including natriuretic peptides. In this study, we investigated the effects of 8 weeks' treatment with sacubitril/valsartan on whole-body and adipose tissue lipolysis and lipid oxidation during defined physical exercise compared with the metabolically neutral comparator amlodipine...
January 2018: Hypertension
https://www.readbyqxmd.com/read/29164797/impact-of-systolic-blood-pressure-on-the-safety-and-tolerability-of-initiating-and-up-titrating-sacubitril-valsartan-in-patients-with-heart-failure-and-reduced-ejection-fraction-insights-from-the-titration-study
#17
Michele Senni, John J V McMurray, Rolf Wachter, Hugh F McIntyre, Inder S Anand, Vincenzo Duino, Arnab Sarkar, Victor Shi, Alan Charney
AIMS: The TITRATION trial investigated two strategies to initiate and up-titrate sacubitril/valsartan (LCZ696) to the same target dose, over a condensed (3-week) or conservative (6-week) period, in patients with heart failure with reduced ejection fraction (HFrEF) and systolic blood pressure (SBP) of ≥100 mmHg. This post hoc analysis examined the relationship between baseline SBP at screening and achievement of the target dose of sacubitril/valsartan of 97 mg/103 mg (also termed 'LCZ696 200 mg') twice per day during the study...
November 22, 2017: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29137346/safety-of-the-neprilysin-renin-angiotensin-system-inhibitor-lcz696
#18
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...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29129252/design-for-the-sacubitril-valsartan-lcz696-compared-with-enalapril-study-of-pediatric-patients-with-heart-failure-due-to-systemic-left-ventricle-systolic-dysfunction-panorama-hf-study
#19
RANDOMIZED CONTROLLED TRIAL
Robert Shaddy, Charles Canter, Nancy Halnon, Lazaros Kochilas, Joseph Rossano, Damien Bonnet, Christopher Bush, Ziqiang Zhao, Paul Kantor, Michael Burch, Fabian Chen
BACKGROUND: Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. STUDY DESIGN: This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year)...
November 2017: American Heart Journal
https://www.readbyqxmd.com/read/29042424/angiotensin-ii-receptor-neprilysin-inhibitor-sacubitril-valsartan-improves-endothelial-dysfunction-in-spontaneously-hypertensive-rats
#20
Takunori Seki, Kenichi Goto, Yasuo Kansui, Toshio Ohtsubo, Kiyoshi Matsumura, Takanari Kitazono
BACKGROUND: We have previously demonstrated that antihypertensive treatment with renin-angiotensin system inhibitors restores the impaired endothelium-dependent hyperpolarization (EDH)-mediated responses in spontaneously hypertensive rats (SHRs). Herein, we investigated whether the angiotensin II receptor-neprilysin inhibitor sacubitril/valsartan (LCZ696) would improve reduced EDH-mediated responses and whether LCZ696 would exert additional effects on endothelium-dependent and endothelium-independent vasorelaxation compared with an angiotensin II type 1 receptor blocker alone during hypertension...
October 17, 2017: Journal of the American Heart Association
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