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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
#1
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
#2
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...
July 11, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28963831/-neprilysin-inhibition-and-chronic-kidney-disease
#3
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/28959905/cost-effectiveness-of-sacubitril-valsartan-versus-enalapril-in-patients-with-heart-failure-and-reduced-ejection-fraction
#4
Liang Lin, David Bin-Chia Wu, Mohamed Ismail Abdul Aziz, Raymond Wong, David Sim, Kui Toh Gerard Leong, Yong Quek Wei, Doreen Tan, Kwong Ng
BACKGROUND: Sacubitril/valsartan reduces cardiovascular death and hospitalisations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care. AIMS: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective. METHODS: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan versus enalapril for 66-year-old patients with HF over 10 years...
September 29, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28944989/the-combination-of-valsartan-and-sacubitril-in-the-treatment-of-hypertension-and-heart-failure-an-update
#5
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/28904036/sacubitril-valsartan-novel-therapy-for-heart-failure
#6
Evan Sehn, Terrence McDonald, Adrienne J Lindblad
No abstract text is available yet for this article.
September 2017: Canadian Family Physician Médecin de Famille Canadien
https://www.readbyqxmd.com/read/28890834/the-use-of-a-novel-heart-failure-agent-in-the-treatment-of-pregnancy-associated-cardiomyopathy
#7
Vamsi C Gaddipati, Aarti A Patel, Adam J Cohen
Peripartum cardiomyopathy is an uncommon, pregnancy-related form of dilated cardiomyopathy that is associated with development of new-onset left ventricular dysfunction. Its etiology is presently unknown, but current standard of care involves the use of typical drug therapy for the treatment of heart failure. Pregnancy-associated cardiomyopathy (PACM) is a similar condition that refers to patients who develop such symptoms prior to the last month of pregnancy. We report the case of a nulliparous Caucasian female who develops early, severe PACM during her first pregnancy with postpartum persistence of New York Heart Association class II-III symptoms despite medical therapy...
2017: Case Reports in Cardiology
https://www.readbyqxmd.com/read/28883863/the-evolution-of-natriuretic-peptide-augmentation-in-management-of-heart-failure-and-the-role-of-sacubitril-valsartan
#8
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/28871373/-acute-and-chronic-heart-failure
#9
K-P Kresoja, G Schmidt, B Kherad, F Krackhardt, F Spillmann, C Tschöpe
The initial therapy of chronic heart failure is still based on diuretics, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers and in specific cases mineralocorticoid receptor antagonists. The new European Society of Cardiology (ESC) guidelines published in 2016 introduced angiotensin-receptor-neprilysin inhibitors, such as sacubitril/valsartan (LCZ 696) as new therapeutic agents in patients with chronic and progressive heart failure. New subgroup analyses for LCZ 696 have been published showing a beneficial effect in the context of various comorbidities, such as renal insufficiency, diabetes and hypotension...
September 4, 2017: Herz
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...
August 23, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28840572/pharmacologic-management-for-heart-failure-and-emerging-therapies
#11
REVIEW
Diana H Kim, Feng-Ju Chien, Howard J Eisen
PURPOSE OF REVIEW: This review aims to summarize the growing body of literature of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) with a focus on recent pharmacologics. RECENT FINDINGS: HFrEF continues to be more widely investigated than HFpEF. Ivabradine and combinatorial treatment with sacubitril and valsartan are promising newly approved therapies. Other experimental therapies have emerged, which include Serelaxin, Empagliflozin, Neuregulin, and Omecamtive mecarbil, among others...
August 24, 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28838926/a-comprehensive-functional-assessment-of-carboxylesterase-1-nonsynonymous-polymorphisms
#12
Xinwen Wang, Nada Rida, Jian Shi, Audrey Wu, Barry Bleske, Hao-Jie Zhu
Carboxylesterase 1 (CES1) is the predominant human hepatic hydrolase responsible for the metabolism of many clinically important medications. CES1 expression and activity vary markedly among individuals; and genetic variation is a major contributing factor to CES1 interindividual variability. In the present study, we comprehensively examined the functions of CES1 nonsynonymous single nucleotide polymorphisms (nsSNPs) and haplotypes using transfected cell lines and individual human liver tissues. The 20 candidate variants include CES1 nsSNPs with a minor allele frequency (MAF) > 0...
August 24, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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
#13
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/28800834/benefits-and-harms-of-sacubitril-in-adults-with-heart-failure-and-reduced-left-ventricular-ejection-fraction
#14
REVIEW
Wilbert S Aronow, Tatyana A Shamliyan
The quality of evidence regarding patient-centered outcomes in adults with heart failure (HF) after sacubitril combined with valsartan has not been systematically appraised. We searched 4 databases in February 2017 and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We reviewed 1 meta-analysis and multiple publications of 2 randomized controlled trials (RCT) and 1 unpublished RCT. In adults with HF and reduced ejection fraction, low-quality evidence from 1 RCT of 8,432 patients suggests that sacubitril combined with valsartan reduces all-cause (number needed to treat [NNT] to prevent 1 event [NNTp] = 35) and cardiovascular mortality (NNTp = 32), hospitalization (NNTp = 11), emergency visits (NNTp = 69), and serious adverse effects, leading to treatment discontinuation (NNTp = 63) and improves quality of life when compared with enalapril...
October 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28765411/heart-failure-what-s-new-and-what-s-changed
#15
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...
July 2017: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/28737127/pharmacokinetics-and-safety-of-sacubitril-valsartan-lcz696-in-patients-with-mild-and-moderate-hepatic-impairment%C3%A2
#16
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/28720639/angioedema-spotlight-a-closer-examination-of-sacubitril-valsartan-safety-results
#17
Ryan E Owens, Carrie S Oliphant
Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population...
July 2017: Journal of the American Board of Family Medicine: JABFM
https://www.readbyqxmd.com/read/28714615/-arni-new-abbreviation-for-a-new-class-of-treatment-of-heart-failure
#18
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/28689451/tailoring-therapy-for-ischemic-cardiomyopathy-is-laplace-s-law-enough
#19
EDITORIAL
Srilakshmi M Adhyapak, V Rao Parachuri
The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure...
September 2017: Therapeutic Advances in Cardiovascular Disease
https://www.readbyqxmd.com/read/28689178/sacubitril-valsartan-beyond-natriuretic-peptides
#20
REVIEW
Jagdeep S S Singh, Louise M Burrell, Myriam Cherif, Iain B Squire, Andrew L Clark, Chim C Lang
Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor...
October 2017: Heart: Official Journal of the British Cardiac Society
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