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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
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/29029087/the-effect-of-sacubitril-valsartan-compared-to-olmesartan-on-cardiovascular-remodelling-in-subjects-with-essential-hypertension-the-results-of-a-randomized-double-blind-active-controlled-study
#5
Roland E Schmieder, Frank Wagner, Michael Mayr, Christian Delles, Christian Ott, Christian Keicher, Maja Hrabak-Paar, Tobias Heye, Solveig Aichner, Yasser Khder, Denise Yates, Diego Albrecht, Thomas Langenickel, Patrick Freyhardt, Rolf Janka, Jens Bremerich
Aims: Progressive aortic stiffening eventually leads to left ventricular (LV) hypertrophy and heart failure if left untreated. Anti-hypertensive agents have been shown to reverse this to some extent. The effects of sacubitril/valsartan (LCZ696), a dual-action angiotensin receptor blocker (ARB), and neprilysin inhibitor, on arterial stiffness and LV remodelling have not been investigated. Methods and results: This was a randomized, multi-centre, double-blind, double-dummy, active-controlled, parallel group, study to compare the effects on cardiovascular remodelling of sacubitril/valsartan with those of olmesartan in patients with hypertension and elevated pulse pressure...
September 27, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28992296/efficacy-and-safety-of-sacubitril-valsartan-lcz696-compared-with-olmesartan-in-elderly-asian-patients-%C3%A2-65-years-with-systolic-hypertension
#6
Ouppatham Supasyndh, Jian'an Wang, Kudsia Hafeez, Ying Zhang, Jack Zhang, Hiromi Rakugi
OBJECTIVE: Systolic hypertension is common in elderly patients and remains a challenge to treat effectively. The efficacy and safety of sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, vs. olmesartan was evaluated in elderly Asian patients (≥65 years) with systolic hypertension. METHODS: In this randomized, double-blind, 14-week study, patients initially received once-daily sacubitril/valsartan 100 mg or olmesartan 10 mg, increased to sacubitril/valsartan 200 mg or olmesartan 20 mg at week 4...
November 6, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28963831/-neprilysin-inhibition-and-chronic-kidney-disease
#7
REVIEW
Luca Di Lullo, Claudio Ronco, Antonio Bellasi, Mario Cozzolino, Fulvio Floccari, Vincenzo Barbera, Simone Verdesca, Rodolfo Rivera, Antonio De Pascalis, Anna Mudoni, Antonio Santoro
Patients with chronic kidney disease (CKD) have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to end-stage renal disease (ESRD) Inhibition of neprilysin, in addition to offering a new therapeutic target in patients with heart failure, could represent a potential improvement strategy in cardiovascular and renal outcome of patients with CKD. Inhibition of neprilysin by inhibiting the breakdown of natriuretic peptides, increases their bioavailability resulting in an increase in diuresis and sodium excretion and, in addition to exerting an inhibition of the renin-angiotensin-aldosterone (RAAS) system...
September 28, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28944989/the-combination-of-valsartan-and-sacubitril-in-the-treatment-of-hypertension-and-heart-failure-an-update
#8
REVIEW
Peter Munch Nielsen, Daniela Grimm, Markus Wehland, Ulf Simonsen, Marcus Krüger
A novel antihypertensive drug, LCZ696 (Entresto®), has recently been introduced, which combines the action of an antagonist of the renin-angiotensin-aldosterone system (RAAS), effectively decreasing the blood pressure, with an inhibition of neprilysin, which is responsible for metabolizing natriuretic peptides exerting antihypertensive and antifibrotic effects. In this MiniReview, we describe the pharmacokinetics and pharmacodynamics, efficacy and side effects of the combined angiotensin receptor antagonist and neprilysin inhibitor LCZ696...
September 25, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28883863/the-evolution-of-natriuretic-peptide-augmentation-in-management-of-heart-failure-and-the-role-of-sacubitril-valsartan
#9
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
#10
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...
September 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
#11
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
#12
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
#13
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
#14
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...
September 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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