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https://www.readbyqxmd.com/read/28087688/thirty-years-of-evidence-on-the-efficacy-of-drug-treatments-for-chronic-heart-failure-with-reduced-ejection-fraction-a-network-meta-analysis
#1
Heather Burnett, Amy Earley, Adriaan A Voors, Michele Senni, John J V McMurray, Celine Deschaseaux, Shannon Cope
BACKGROUND: Treatments that reduce mortality and morbidity in patients with heart failure with reduced ejection fraction, including angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), β-blockers (BB), mineralocorticoid receptor antagonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNI), have not been studied in a head-to-head fashion. This network meta-analysis aimed to compare the efficacy of these drugs and their combinations regarding all-cause mortality in patients with heart failure with reduced ejection fraction...
January 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28078611/hyperbaric-oxygen-prevents-cognitive-impairments-in-mice-induced-by-d-galactose-by-improving-cholinergic-and-anti-apoptotic-functions
#2
Chunxia Chen, Luying Huang, Zhihuan Nong, Yaoxuan Li, Wan Chen, Jianping Huang, Xiaorong Pan, Guangwei Wu, Yingzhong Lin
Our previous study demonstrated that hyperbaric oxygen (HBO) improved cognitive impairments mainly by regulating oxidative stress, inflammatory responses and aging-related gene expression. However, a method for preventing cognitive dysfunction has yet to be developed. In the present study, we explored the protective effects of HBO on the cholinergic system and apoptosis in D-galactose (D-gal)-treated mice. A model of aging was established via systemic intraperitoneal injection of D-gal daily for 8 weeks. HBO was administered during the last 2 weeks of D-gal injection...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28076404/combined-inhibition-of-the-renin-angiotensin-system-and-neprilysin-positively-influences-complex-mitochondrial-adaptations-in-progressive-experimental-heart-failure
#3
Laura Grois, Julian Hupf, Jörg Reinders, Josef Schröder, Alexander Dietl, Peter M Schmid, Carsten Jungbauer, Markus Resch, Lars S Maier, Andreas Luchner, Christoph Birner
BACKGROUND: Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). METHODS AND RESULTS: By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL)...
2017: PloS One
https://www.readbyqxmd.com/read/28075105/heart-failure-due-to-reduced-ejection-fraction-medical-management
#4
William E Chavey, Robrt V Hogikyan, R Van Harrison, John M Nicklas
Heart failure is an increasingly common condition resulting in high rates of morbidity and mortality. For patients who have heart failure and reduced ejection fraction, randomized clinical trials demonstrate consistent mortality benefit from angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, direct-acting vasodilators, beta blockers, and aldosterone antagonists. Additionally, some data show benefits from two new classes of drugs: angiotensin receptor blocker/neprilysin inhibitor and sinus node modulator...
January 1, 2017: American Family Physician
https://www.readbyqxmd.com/read/28062615/biochemistry-therapeutics-and-biomarker-implications-of-neprilysin-in-cardiorenal-disease
#5
REVIEW
Yang Chen, John C Burnett
BACKGROUND: Neprilysin (NEP) is a membrane-bound neutral endopeptidase that degrades a variety of bioactive peptides. The substrates include natriuretic peptides (NPs), which are important regulating mediators for cardiovascular and renal biology. Inhibition of NEP activity and exogenous NP administration thus have emerged as potential therapeutic strategies for treating cardiorenal diseases. More recently, B-type natriuretic peptide (BNP) or N-terminal-proBNP (NT-proBNP), 3'-5' cyclic guanosine monophosphate (cGMP), and soluble NEP as biomarkers have also been investigated in heart failure (HF) trials and their predictive value are beginning to be recognized...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28060547/the-safety-of-sacubitril-valsartan-for-the-treatment-of-chronic-heart-failure
#6
Jeffrey M Tyler, John R Teerlink
Sacubitril-valsartan is a combination drug that contains the neprilysin inhibitor sacubitril and angiotensin II receptor blocker valsartan. In 2015, the US Food and Drug Administration approved sacubitril-valsartan for treatment of heart failure patients with reduced ejection fraction and New York Heart Association class II-IV symptoms following a large, Phase III clinical trial (PARADIGM-HF) that demonstrated a 20% reduction in the combined primary end-point of death from cardiovascular cause or hospitalization for heart failure compared to enalapril...
January 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28040864/glp-1-receptor-independent-pathways-emerging-beneficial-effects-of-glp-1-breakdown-products
#7
REVIEW
Valeria Guglielmi, Paolo Sbraccia
The glucagon-like peptide-1 (GLP-1) axis has emerged as a major therapeutic target for the treatment of type 2 diabetes and, recently, of obesity. The insulinotropic activity of the native incretin hormone GLP-1(7-36)amide, which is mainly exerted through a unique G protein-coupled receptor (GLP-1R), is terminated via enzymatic cleavage by dipeptidyl peptidase-IV that generates a C-terminal GLP-1 metabolite GLP-1(9-36)amide, the major circulating form in plasma. GLP-1(28-36)amide and GLP-1(32-36)amide are further cleavage products derived from GLP-1(7-36)amide and GLP-1(9-36)amide by the action of a neutral endopeptidase known as neprilysin...
December 31, 2016: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28030431/efficacy-and-safety-of-sacubitril-valsartan-lcz696-add-on-to-amlodipine-in-asian-patients-with-systolic-hypertension-uncontrolled-with-amlodipine-monotherapy
#8
Ji-Guang Wang, Kimihiko Yukisada, Antonio Sibulo, Kudsia Hafeez, Yan Jia, Jack Zhang
OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of sacubitril/valsartan (LCZ696, an angiotensin receptor and neprilysin inhibitor) add-on to amlodipine compared with amlodipine monotherapy in Asian patients with systolic hypertension uncontrolled with amlodipine. METHODS: Patients with mean clinic SBP at least 145 mmHg and less than 180 mmHg after a 4-week treatment with amlodipine 5 mg/day were randomized to receive LCZ696/amlodipine (200/5 mg/day) or amlodipine 5 mg/day for 8 weeks...
December 24, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/28024961/efficacy-and-safety-of-sacubitril-valsartan-lcz696-in-japanese-patients-with-chronic-heart-failure-and-reduced-ejection-fraction-rationale-for-and-design-of-the-randomized-double-blind-parallel-hf-study
#9
Hiroyuki Tsutsui, Shinichi Momomura, Yoshihiko Saito, Hiroshi Ito, Kazuhiro Yamamoto, Tomomi Ohishi, Naoko Okino, Weinong Guo
BACKGROUND: The prognosis of heart failure patients with reduced ejection fraction (HFrEF) in Japan remains poor, although there is growing evidence for increasing use of evidence-based pharmacotherapies in Japanese real-world HF registries. Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor shown to reduce mortality and morbidity in the recently completed largest outcome trial in patients with HFrEF (PARADIGM-HF trial). The prospectively designed phase III PARALLEL-HF (Prospective comparison of ARNI with ACE inhibitor to determine the noveL beneficiaL trEatment vaLue in Japanese Heart Failure patients) study aims to assess the clinical efficacy and safety of LCZ696 in Japanese HFrEF patients, and show similar improvements in clinical outcomes as the PARADIGM-HF study enabling the registration of LCZ696 in Japan...
December 23, 2016: Journal of Cardiology
https://www.readbyqxmd.com/read/28004291/sacubitril-valsartan-lcz696-in-heart-failure
#10
Yasser Khder, Victor Shi, John J V McMurray, Martin P Lefkowitz
It has been known since the 1990s that long-term morbidity and mortality is improved in patients with heart failure with reduced ejection fraction (HFrEF) by treatments that target the renin-angiotensin-aldosterone system (RAAS). It has also long been thought that enhancement of the activity of natriuretic peptides (NPs) could potentially benefit patients with HFrEF, but multiple attempts to realize this benefit had failed over the years - until 2014, when a large, phase III, randomized, controlled clinical trial (PARADIGM-HF) was completed comparing sacubitril/valsartan with enalapril, a well-established treatment for HFrEF...
December 22, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27974807/long-term-neprilysin-inhibition-implications-for-arnis
#11
REVIEW
Duncan J Campbell
Neprilysin has a major role in both the generation and degradation of bioactive peptides. LCZ696 (valsartan/sacubitril, Entresto), the first of the new ARNI (dual-acting angiotensin-receptor-neprilysin inhibitor) drug class, contains equimolar amounts of valsartan, an angiotensin-receptor blocker, and sacubitril, a prodrug for the neprilysin inhibitor LBQ657. LCZ696 reduced blood pressure more than valsartan alone in patients with hypertension. In the PARADIGM-HF study, LCZ696 was superior to the angiotensin-converting enzyme inhibitor enalapril for the treatment of heart failure with reduced ejection fraction, and LCZ696 was approved by the FDA for this purpose in 2015...
December 15, 2016: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27957625/a-genome-wide-analysis-in-cluster-headache-points-to-neprilysin-and-pacap-receptor-gene-variants
#12
Elena Bacchelli, Maria Michela Cainazzo, Cinzia Cameli, Simona Guerzoni, Angela Martinelli, Michele Zoli, Elena Maestrini, Luigi Alberto Pini
BACKGROUND: Cluster Headache (CH) is a severe primary headache, with a poorly understood pathophysiology. Complex genetic factors are likely to play a role in CH etiology; however, no confirmed gene associations have been identified. The aim of this study is to identify genetic variants influencing risk to CH and to explore the potential pathogenic mechanisms. METHODS: We have performed a genome-wide association study (GWAS) in a clinically well-defined cohort of 99 Italian patients with CH and in a control sample of 360 age-matched sigarette smoking healthy individuals, using the Infinium PsychArray (Illumina), which combines common highly-informative genome-wide tag SNPs and exonic SNPs...
December 2016: Journal of Headache and Pain
https://www.readbyqxmd.com/read/27956439/heart-failure-what-s-new-and-what-s-changed
#13
Paul D Callan, Andrew L Clark
Physicians responsible for the care of patients with heart failure due to left ventricular systolic dysfunction have access to a broad range of evidence-based treatments that prolong life and reduce symptoms. In spite of the significant progress made over the last four decades, there is an ongoing need for novel therapies to treat a condition that is associated with stubbornly high morbidity and mortality. In this article, we discuss the findings of SERVE-HF, a randomised controlled trial of adaptive servo-ventilation in patients with left ventricular systolic dysfunction, as well as EMPA-REG, a study of the effects of a novel diabetic agent that may be of greater interest to heart failure specialists than diabetologists...
December 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/27951594/beneficial-effects-of-combined-at1-receptor-neprilysin-inhibition-arni-versus-at1-receptor-blockade-alone-in-the-diabetic-eye
#14
Tuhina Prasad, Lodi C W Roksnoer, Ping Zhu, Amrisha Verma, Yiming Li, Wendy W Batenburg, René de Vries, A H Jan Danser, Qiuhong Li
Purpose: Dysfunction of the renin-angiotensin system (RAS) contributes to pathogenesis of diabetic retinopathy (DR). Yet RAS blockers have only limited beneficial effects on progression of DR in clinical trials. The natriuretic peptide system offsets RAS, so that enhancing the activity of this system on top of RAS blockade might be beneficial. Neprilysin has an important role in the degradation of natriuretic peptides. Therefore, we hypothesize that dual angiotensin receptor-neprilysin inhibition (ARNI) may outperform angiotensin receptor blocker (ARB) in protection against DR...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27933334/improved-glycaemia-in-high-fat-fed-neprilysin-deficient-mice-is-associated-with-reduced-dpp-4-activity-and-increased-active-glp-1-levels
#15
Joshua R Willard, Breanne M Barrow, Sakeneh Zraika
AIM/HYPOTHESIS: Neprilysin, a widely expressed peptidase, is upregulated in metabolically altered states such as obesity and type 2 diabetes. Like dipeptidyl peptidase-4 (DPP-4), neprilysin can degrade and inactivate the insulinotropic peptide glucagon-like peptide-1 (GLP-1). Thus, we investigated whether neprilysin deficiency enhances active GLP-1 levels and improves glycaemia in a mouse model of high fat feeding. METHODS: Nep (+/+) and Nep (-/-) mice were fed a 60% fat diet for 16 weeks, after which active GLP-1 and DPP-4 activity levels were measured, as were glucose, insulin and C-peptide levels during an OGTT...
December 8, 2016: Diabetologia
https://www.readbyqxmd.com/read/27919443/importance-of-endogenous-compensatory-vasoactive-peptides-in-broadening-the-effects-of-inhibitors-of-the-renin-angiotensin-system-for-the-treatment-of-heart-failure
#16
REVIEW
Milton Packer, John J V McMurray
The magnitude of the clinical benefits produced by inhibitors of the renin-angiotensin system in heart failure has been modest, possibly because of the ability of renin-angiotensin activity to escape from suppression during long-term treatment. Efforts to intensify pharmacological blockade by use of dual inhibitors that interfere with the renin-angiotensin system at multiple sites have not yielded consistent incremental clinical benefits, but have been associated with serious adverse reactions. By contrast, potentiation of endogenous compensatory vasoactive peptides can act to enhance the survival effects of inhibitors of the renin-angiotensin system, as evidenced by trials that have compared angiotensin-converting enzyme inhibitors with drugs that inhibit both the renin-angiotensin system and neprilysin...
December 2, 2016: Lancet
https://www.readbyqxmd.com/read/27919317/drosophila-neprilysins-control-insulin-signaling-and-food-intake-via-cleavage-of-regulatory-peptides
#17
Benjamin Hallier, Ronja Schiemann, Eva Cordes, Jessica Vitos-Faleato, Stefan Walter, Jürgen J Heinisch, Anders Malmendal, Achim Paululat, Heiko Meyer
Insulin and IGF signaling are critical to numerous developmental and physiological processes, with perturbations being pathognomonic of various diseases, including diabetes. Although the functional roles of the respective signaling pathways have been extensively studied, the control of insulin production and release is only partially understood. Herein, we show that in Drosophila expression of insulin-like peptides is regulated by neprilysin activity. Concomitant phenotypes of altered neprilysin expression included impaired food intake, reduced body size, and characteristic changes in the metabolite composition...
December 6, 2016: ELife
https://www.readbyqxmd.com/read/27908347/prognostic-implications-of-changes-in-n-terminal-pro-b-type-natriuretic-peptide-in-patients-with-heart-failure
#18
Michael R Zile, Brian L Claggett, Margaret F Prescott, John J V McMurray, Milton Packer, Jean L Rouleau, Karl Swedberg, Akshay S Desai, Jianjian Gong, Victor C Shi, Scott D Solomon
BACKGROUND: Natriuretic peptides (NP) have prognostic value in heart failure (HF), although the clinical importance of changes in NP from baseline is unclear. OBJECTIVES: The authors assessed whether a reduction in N-terminal pro-B-type NP (NT-proBNP) was associated with a decrease in HF hospitalization and cardiovascular mortality (primary endpoint) in patients with HF and reduced ejection fraction, whether treatment with sacubitril/valsartan reduced NT-proBNP below specific partition values more than enalapril, and whether the relationship between changes in NT-proBNP and changes in the primary endpoint were dependent on assigned treatment...
December 6, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27905476/heart-failure-neprilysin-inhibition-attenuates-risk-of-hyperkalaemia-in-hfref
#19
Karina Huynh
No abstract text is available yet for this article.
January 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/27895004/predictors-of-vascular-cognitive-impairment-poststroke-in-a-middle-eastern-bahrain-cohort-a-proposed-case-control-comparison
#20
Claire Donnellan, Mona Al Banna, Noor Redha, Adel Al Jishi, Isa Al Sharoqi, Safa Taha, Moiz Bakhiet, Fatema Abdulla, Patrick Walsh
BACKGROUND: Poststroke dementia and cognitive impairment are associated with poor long-term outcomes after stroke. The contribution of genetic factors such as the presence of apolipoprotein (ApoE) ɛ4 allele and its association with cognitive impairment poststroke remains inconclusive, particularly in Middle Eastern regions. OBJECTIVE: The aim of this study is to examine all correlates and potential predictors of cognitive impairment including self-awareness and regulation deficits in stroke patients and compare these functions with healthy older adults from a Middle Eastern population...
November 28, 2016: JMIR Research Protocols
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