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https://www.readbyqxmd.com/read/29661699/effect-of-neprilysin-inhibition-on-renal-function-in-patients-with-type-2-diabetes-and-chronic-heart-failure-who-are-receiving-target-doses-of-inhibitors-of-the-renin-angiotensin-system-a-secondary-analysis-of-the-paradigm-hf-trial
#1
Milton Packer, Brian Claggett, Martin P Lefkowitz, John J V McMurray, Jean L Rouleau, Scott D Solomon, Michael R Zile
BACKGROUND: Neprilysin inhibition has favourable effects on experimental diabetic nephropathy. We sought to assess the effects of neprilysin inhibition on the course of renal function in patients with type 2 diabetes. METHODS: In the randomised, double-blind PARADIGM-HF trial, the effects of sacubitril/valsartan (97 mg/103 mg twice daily) were compared with enalapril (10 mg twice daily) in 8399 patients with mild-to-moderate chronic heart failure and systolic dysfunction...
April 13, 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29655829/renal-effects-and-associated-outcomes-during-angiotensin-neprilysin-inhibition-in-heart-failure
#2
Kevin Damman, Mauro Gori, Brian Claggett, Pardeep S Jhund, Michele Senni, Martin P Lefkowitz, Margaret F Prescott, Victor C Shi, Jean L Rouleau, Karl Swedberg, Michael R Zile, Milton Packer, Akshay S Desai, Scott D Solomon, John J V McMurray
OBJECTIVES: The purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction. BACKGROUND: Renal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate further after blockade of the renin-angiotensin system. METHODS: In the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibition to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial, 8,399 patients with heart failure with reduced ejection fraction were randomized to treatment with sacubitril/valsartan or enalapril...
April 5, 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29643067/incidence-predictors-and-outcomes-associated-with-hypotensive-episodes-among-heart-failure-patients-receiving-sacubitril-valsartan-or-enalapril-the-paradigm-hf-trial-prospective-comparison-of-angiotensin-receptor-neprilysin-inhibitor-with-angiotensin-converting
#3
Orly Vardeny, Brian Claggett, Jessica Kachadourian, Scott M Pearson, Akshay S Desai, Milton Packer, Jean Rouleau, Michael R Zile, Karl Swedberg, Martin Lefkowitz, Victor Shi, John J V McMurray, Scott D Solomon
BACKGROUND: In PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure), heart failure treatment with sacubitril/valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared with enalapril but resulted in more symptomatic hypotension. Concern on hypotension may be limiting use of sacubitril/valsartan in appropriate patients...
April 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29623127/heterogeneous-pd-catalysts-as-emulsifiers-in-pickering-emulsions-for-integrated-multistep-synthesis-in-flow-chemistry
#4
Katharina Hiebler, Georg J Lichtenegger, Manuel C Maier, Eun Sung Park, Renie Gonzales-Groom, Bernard P Binks, Heidrun Gruber-Woelfler
Within the "compartmentalised smart factory" approach of the ONE-FLOW project the implementation of different catalysts in "compartments" provided by Pickering emulsions and their application in continuous flow is targeted. We present here the development of heterogeneous Pd catalysts that are ready to be used in combination with biocatalysts for catalytic cascade synthesis of active pharmaceutical ingredients (APIs). In particular, we focus on the application of the catalytic systems for Suzuki-Miyaura cross-coupling reactions, which is the key step in the synthesis of the targeted APIs valsartan and sacubitril...
2018: Beilstein Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29617523/effects-of-sacubitril-valsartan-on-physical-and-social-activity-limitations-in-patients-with-heart-failure-a-secondary-analysis-of-the-paradigm-hf-trial
#5
Alvin Chandra, Eldrin F Lewis, Brian L Claggett, Akshay S Desai, Milton Packer, Michael R Zile, Karl Swedberg, Jean L Rouleau, Victor C Shi, Martin P Lefkowitz, Tzvetana Katova, John J V McMurray, Scott D Solomon
Importance: Health-related quality of life (HRQL) of patients with heart failure is markedly reduced compared with that in patients with other chronic diseases, demonstrating substantial limitations in physical and social activities. In the Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, sacubitril/valsartan improved overall HRQL compared with enalapril, as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ)...
April 4, 2018: JAMA Cardiology
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
#6
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/29608504/inter-atrial-shunting-a-novel-device-based-therapy-for-patients-with-heart-failure
#7
Brian Kw Yum, William H Frishman
Heart failure patients with either reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF) experience a high mortality rate. The most recent pharmacologic advance for treating patients with HFrEF has been with sacubitril/valsartan. Along with pharmaceutical research, there has been interest in device-based therapies as another treatment approach. One novel interventional device therapy that has shown promise in early tests and trials is the inter-atrial shunt device developed by Corvia Medical Inc...
March 30, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29603541/augmentation-of-glucagon-like-peptide-1-receptor-signalling-by-neprilysin-inhibition-potential-implications-for-patients-with-heart-failure
#8
REVIEW
Milton Packer
Augmentation of glucagon-like peptide-1 (GLP-1) receptor signalling is an established approach to the treatment of type 2 diabetes. However, endogenous GLP-1 and long-acting GLP-1 receptor analogues are degraded not only by dipeptidyl peptidase-4, but also by neprilysin. This observation raises the possibilities that endogenous GLP-1 contributes to the clinical effects of neprilysin inhibition and that patients concurrently treated with sacubitril/valsartan and incretin-based drugs may experience important drug-drug interactions...
March 30, 2018: European Journal of Heart Failure
https://www.readbyqxmd.com/read/29601093/cost-effectiveness-analysis-of-sacubitril-valsartan-for-the-treatment-of-heart-failure-with-reduced-ejection-fraction-in-the-united-states
#9
Patrick M Zueger, Varun M Kumar, Rachel L Harrington, Gianna C Rigoni, Alicia Atwood, Robert J DiDomenico, Daniel R Touchette
OBJECTIVE: Sacubitril/valsartan (SAC/VAL) has been shown to reduce mortality and hospitalization in patients with heart failure with reduced ejection fraction (HFrEF) compared with enalapril, but at a substantially higher cost. This study evaluates the cost-effectiveness of SAC/VAL versus enalapril in patients with HFrEF over a 5-year time horizon from the US payer perspective. METHODS: A cohort-based Markov model was developed to compare costs and quality-adjusted life years (QALYs) between SAC/VAL and enalapril in patients with HFrEF over a 5 year time horizon...
March 30, 2018: Pharmacotherapy
https://www.readbyqxmd.com/read/29595329/sacubitril-and-valsartan-protect-from-experimental-myocardial-infarction-by-ameliorating-oxidative-damage-in-wistar-rats
#10
Mohd Imran, Md Quamrul Hassan, Md Sayeed Akhtar, Obaid Rahman, M Akhtar, Abul Kalam Najmi
BACKGROUND: Sacubitril (SAC), a neprilysin inhibitor prevent degradation of neprilysin and activate cGMP signaling pathways leading to rise in blood volume concurrent to blood pressure by means of vasoactive peptides, adrenomedullin, and bradykinin. OBJECTIVE: The aim of this study was to evaluate the anti-ischemic effects of SAC through inhibiting neprilysin in isoproterenol (ISO) induced myocardial infarction (MI) in Wistar albino rats. ISO (85 mg/kg) was injected subcutaneously at the end of 14 days pre-treatment with SAC and valsartan (VAL)...
March 29, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29589064/recent-major-advances-in-cardiovascular-pharmacotherapy
#11
REVIEW
James Milner, Andreia Cunha, Carlota Gamboa-Cruz, Julie Reis, Márcia Campos, Natália António
The field of cardiovascular pharmacotherapy remains extremely active. The aim of this review is to summarize the recent major advances in cardiovascular pharmacotherapy, with a focus on (1) the new approved drug for treatment of heart failure with reduced ejection fraction-sacubitril/valsartan; (2) proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors; (3) the novel reversal agents for non-vitamin K oral anticoagulants (NOACs); and finally, (4) new evidence on pharmacological treatment of coronary artery disease...
March 27, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29544929/angiotensin-receptor-neprilysin-inhibition-provides-superior-cardioprotection-compared-to-angiotensin-converting-enzyme-inhibition-after-experimental-myocardial-infarction
#12
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/29532764/entresto-a-new-panacea-for-heart-failure
#13
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/29526184/chronic-heart-failure
#14
Frank Edelmann, Christoph Knosalla, Klaus Mörike, Christiane Muth, Peggy Prien, Stefan Störk
BACKGROUND: Chronic heart failure (CHF) is the most common reason for hospital admissions in Germany. For the National Disease Management Guideline (NDMG) on CHF, a multidisciplinary expert panel revised the chapters on drug therapy, invasive therapy, and care coordination, following the methods of evidence-based medicine. METHODS: Recommendations are based on international guideline adaptations or systematic literature search. They were developed by a multidisciplinary expert panel, approved in a formal consensus procedure, and tested in open consultation, as specified by the requirements for S3 guidelines...
February 23, 2018: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/29520644/in-hfref-patients-sacubitril-valsartan-given-at-relatively-low-doses-does-not-lead-to-increased-mortality-or-hospitalization-a-retrospective-cohort-study
#15
R De Vecchis, C Ariano, G Di Biase, M Noutsias
INTRODUCTION: In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. MATERIAL AND METHODS: This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan...
March 8, 2018: Herz
https://www.readbyqxmd.com/read/29512176/three-case-reports-of-involuntary-muscular-movements-as-adverse-reactions-to-sacubitril-valsartan
#16
Theodora Bejan-Angoulvant, Thibaud Genet, Laura Vrignaud, Denis Angoulvant, Laurent Fauchier
No abstract text is available yet for this article.
March 6, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29502102/combined-angiotensin-receptor-neprilysin-inhibitors-improve-cardiac-and-vascular-function-via-increased-no-bioavailability-in-heart-failure
#17
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/29501368/-a-novel-agent-in-the-treatment-of-heart-failure-with-depressed-systolic-function
#18
Yan C Duarte Vera, Silvia V Cáceres Vinueza, Jorge E Daher Nader, Joffre F Lara Terán
INTRODUCTION: A review is presented on the evolution of the pharmacological treatment of heart failure (HF) in the last 25 years, from the concept of treatment with vasodilators to the blocking or inhibition of the renin angiotensin aldosterone system. Beta-adrenergic inhibition and its important contribution in the reduction of morbidity and mortality due to HF will be discussed along with the role of the natriuretic peptides. One of the most important studies in the cardiology area, and specifically in the management of HF, is presented, in which an approach is demonstrated of the modulator of the neurohumoral systems that are activated in these patients...
February 28, 2018: Archivos de Cardiología de México
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
#19
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/29496376/-atrial-natriuretic-hormones-and-metabolic-syndrome-recent-advances
#20
Kanza Benomar, Stéphanie Espiard, Camille Loyer, Arnaud Jannin, Marie-Christine Vantyghem
Natriuretic peptides are a group of hormones including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C type (CNP), urodilatin and guanilyn. ANP (half-life: 2-4 min), is secreted by the atrium, BNP (half-life: 20 min) by the ventricle, CNP by the vascular endothelium, urodilatin by the kidney and guanylin by the intestine. These natriuretic peptides prevent water and salt retention through renal action, vasodilatation and hormonal inhibition of aldosterone, vasopressin and cortisol. These peptides also have a recently demonstrated metabolic effect through an increase of lipolysis, thermogenesis, beta cell proliferation and muscular sensitivity to insulin...
February 26, 2018: La Presse Médicale
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