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Sacubitril/valsartan

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https://www.readbyqxmd.com/read/29771478/the-reverse-remodeling-response-to-sacubitril-valsartan-therapy-in-heart-failure-with-reduced-ejection-fraction
#1
Pieter Martens, Hanne Beliën, Matthias Dupont, Pieter Vandervoort, Wilfried Mullens
BACKGROUND: Major classes of medical therapy for heart failure with reduced ejection fraction (HFrEF) induce reverse remodeling. The revere remodeling response to sacubitril/valsartan remains unstudied. METHODS: We performed a single-center, prospective assessor-blinded study to determine the reverse remodeling response of sacubitril/valsartan-therapy in HFrEF-patients with a class I-indication (New York heart Association [NYHA]-class II-IV, Left ventricular ejection fraction [LVEF]<35%, optimal dose with Renin-Angiotensin-System-Blocker [RAS-blocker])...
May 17, 2018: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29761293/stable-but-progressive-nature-of-heart-failure-considerations-for-primary-care-physicians
#2
REVIEW
Inder Anand
Primary care physicians play a significant role in managing heart failure (HF), with the goals of reducing mortality, avoiding hospitalization, and improving patients' quality of life. Most HF-related hospitalizations and deaths occur in patients with New York Heart Association functional class II or III, many of whom are perceived to have stable disease, which often progresses without clinical symptoms due to underlying deleterious effects of neurohormonal imbalance and endothelial dysfunction. Management includes lifestyle changes and stepped pharmacological therapy directed at the four stages of HF, with aggressive uptitration of therapies, including beta-blockers and inhibitors of the renin-angiotensin-aldosterone system...
May 14, 2018: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/29754651/rationale-and-methods-of-the-prospective-study-of-biomarkers-symptom-improvement-and-ventricular-remodeling-during-sacubitril-valsartan-therapy-for-heart-failure-prove-hf
#3
James L Januzzi, Javed Butler, Emmanuel Fombu, Alan Maisel, Kevin McCague, Ileana L Piña, Margaret F Prescott, Jerome B Riebman, Scott Solomon
BACKGROUND: Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. METHODS: This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy...
May 2018: American Heart Journal
https://www.readbyqxmd.com/read/29748349/independent-prognostic-value-of-serum-soluble-st2-measurements-in-patients-with-heart-failure-and-a-reduced-ejection-fraction-in-the-paradigm-hf-trial-prospective-comparison-of-arni-with-acei-to-determine-impact-on-global-mortality-and-morbidity-in-heart-failure
#4
Eileen O'Meara, Margaret F Prescott, Brian Claggett, Jean L Rouleau, Lu-May Chiang, Scott D Solomon, Milton Packer, John J V McMurray, Michael R Zile
BACKGROUND: Soluble ST2 (sST2) is associated with cardiac remodeling and fibrosis. In chronic heart failure, the predictive value of sST2 has not been evaluated in a model that includes both NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity cardiac troponin T), in a trial in which treatment had a major impact. Therefore, the effects of treatment on sST2 levels in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the relationships between sST2 and outcomes, and the prognostic utility of various sST2 partition values were examined...
May 2018: Circulation. Heart Failure
https://www.readbyqxmd.com/read/29746915/cognition-and-dementia-related-adverse-effects-with-sacubitril-valsartan-analysis-of-the-fda-adverse-event-report-system-database
#5
Amichai Perlman, Bruria Hirsh Raccah, Ilan Matok, Mordechai Muszkat
BACKGROUND: As neprilysin is involved in the degradation of amyloid-beta, there is concern the angiotensin-neprilysin inhibitor, sacubitril-valsartan, could increase the risk for dementia. METHODS: We analyzed adverse event cases submitted to the FDA adverse event report system between July 2015 and March 2017. Cognition and dementia related adverse event cases were defined using broad and narrow structured medical queries. RESULTS: During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan...
May 7, 2018: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/29746914/cognition-and-dementia-related-adverse-effects-with-sacubitril-valsartan-analysis-of-the-fda-adverse-event-report-system-database
#6
Amichai Perlman, Bruria Hirsh Raccah, Ilan Matok, Mordechai Muszkat
BACKGROUND: As neprilysin is involved in the degradation of amyloid-beta, there is concern the angiotensin-neprilysin inhibitor, sacubitril-valsartan, could increase the risk for dementia. METHODS: We analyzed adverse event cases submitted to the FDA adverse event report system between July 2015 and March 2017. Cognition and dementia related adverse event cases were defined using broad and narrow structured medical queries. RESULTS: During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan...
May 7, 2018: Journal of Cardiac Failure
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
#7
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/29687191/sacubitril-valsartan-from-clinical-trials-to-real-world-experience
#8
REVIEW
Joanna M Joly, Akshay S Desai
PURPOSE OF REVIEW: Compared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan. RECENT FINDINGS: In the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectrum of patients with HFrEF...
April 23, 2018: Current Treatment Options in Cardiovascular Medicine
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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 U.S. 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
#18
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
#19
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
#20
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
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