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https://www.readbyqxmd.com/read/27908347/prognostic-implications-of-changes-in-n-terminal-pro-b-type-natriuretic-peptide-in-patients-with-heart-failure
#1
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/27868321/dementia-related-adverse-events-in-paradigm-hf-and-other-trials-in-heart-failure-with-reduced-ejection-fraction
#2
Jane A Cannon, Li Shen, Pardeep S Jhund, Søren L Kristensen, Lars Køber, Fabian Chen, Jianjian Gong, Martin P Lefkowitz, Jean L Rouleau, Victor C Shi, Karl Swedberg, Michael R Zile, Scott D Solomon, Milton Packer, John J V McMurray
AIMS: Inhibition of neprilysin, an enzyme degrading natriuretic and other vasoactive peptides, is beneficial in heart failure with reduced ejection fraction (HFrEF), as shown in PARADIGM-HF which compared the angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan with enalapril. As neprilysin is also one of many enzymes clearing amyloid-β peptides from the brain, there is a theoretical concern about the long-term effects of sacubitril/valsartan on cognition. Therefore, we have examined dementia-related adverse effects (AEs) in PARADIGM-HF and placed these findings in the context of other recently conducted HFrEF trials...
November 20, 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27858191/focus-on-the-novel-cardiovascular-drug-lzc696-from-evidence-to-clinical-consideration
#3
L M Lin, Y Wu, M F Wu, J X Lin
LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), is comprised of the angiotensin receptor blocker valsartan and the neprilysin inhibitor pro-drug sacubitril (AHU377). After oral administration, AHU377 is rapidly metabolized to the active neprilysin inhibitor LBQ657. LCZ696 exerts its effects of diuresis, natriuresis, vasodilation and aldosterone secretion inhibition through simultaneous renin-angiotensin-aldosterone system (RAAS) blockade and natriuretic peptides system (NPS) enhancement...
November 18, 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27858115/-the-new-esc-guidelines-for-acute-and-chronic-heart-failure-2016
#4
C U Oeing, C Tschöpe, B Pieske
The new guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) were presented in May 2016 during the congress of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in Florence. An important amendment affects the classification of HF which now differentiates between HF with preserved ejection fraction (HFpEF) and left ventricular EF (LVEF) > 50%, HF with reduced ejection fraction (HFrEF, LVEF < 40%) and the new entity HF with mid-range ejection fraction (HFmrEF, LVEF 40-49%)...
December 2016: Herz
https://www.readbyqxmd.com/read/27853163/long-term-52-week-safety-and-efficacy-of-sacubitril-valsartan-in-asian-patients-with-hypertension
#5
Ouppatham Supasyndh, Ningling Sun, Kazuomi Kario, Kudsia Hafeez, Jack Zhang
Sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor-neprilysin inhibitor, demonstrated significant reductions in office and 24 h ambulatory blood pressure (BP) over 8 weeks in Asian patients with hypertension. This 52-week extension to the 8-week core study was aimed at evaluating the long-term safety, tolerability and efficacy of sacubitril/valsartan. Patients who completed an 8-week randomized study (the core study) were enrolled in this 52-week open-label study and received sacubitril/valsartan 200 mg QD...
November 17, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27849566/effects-of-sacubitril-valsartan-lcz696-on-natriuresis-diuresis-blood-pressures-and-nt-probnp-in-salt-sensitive-hypertension
#6
Tzung-Dau Wang, Ru-San Tan, Hae-Young Lee, Sang-Hyun Ihm, Moo-Yong Rhee, Brian Tomlinson, Parasar Pal, Fan Yang, Elizabeth Hirschhorn, Margaret F Prescott, Markus Hinder, Thomas H Langenickel
: Salt-sensitive hypertension (SSH) is characterized by impaired sodium excretion and subnormal vasodilatory response to salt loading. Sacubitril/valsartan (LCZ696) was hypothesized to increase natriuresis and diuresis and result in superior blood pressure control compared with valsartan in Asian patients with SSH. In this randomized, double-blind, crossover study, 72 patients with SSH received sacubitril/valsartan 400 mg and valsartan 320 mg once daily for 4 weeks each. SSH was diagnosed if the mean arterial pressure increased by ≥10% when patients switched from low (50 mmol/d) to high (320 mmol/d) sodium diet...
November 14, 2016: Hypertension
https://www.readbyqxmd.com/read/27837397/from-arb-to-arni-in-cardiovascular-control
#7
REVIEW
Estrellita Uijl, Lodi C W Roksnoer, Ewout J Hoorn, A H Jan Danser
Coexistence of hypertension, diabetes mellitus and chronic kidney disease synergistically aggravates the risk of cardiovascular and renal morbidity and mortality. These high-risk, multi-morbid patient populations benefit less from currently available anti-hypertensive treatment. Simultaneous angiotensin II type 1 receptor blockade and neprilysin inhibition ('ARNI') with valsartan/sacubitril (LCZ696) might potentiate the beneficial effects of renin-angiotensin-aldosterone inhibition by reinforcing its endogenous counterbalance, the natriuretic peptide system...
December 2016: Current Hypertension Reports
https://www.readbyqxmd.com/read/27824422/-sacubitril-valsartan-in-patients-with-diabetes-and-heart-failure
#8
Vincent Matthias Brandenburg, Hans-Peter Brunner-La Rocca, Nikolaus Marx
Sacubitril / Valsartan proofed to be an effective treatment compared to enalapril in reducing heart failure hospitalisations and mortality in patients with severe "Heart failure with reduced ejection fraction" (HFREF). Recent European cardiology guidelines attributed a class IB recommendation for Sacubitril / Valsartan in HFREF patients who remain symptomatic despite optimal treatment with ACE-I, a beta-blocker, and a mineralocorticoid receptor antagonist. There is a significant overlap between diabetic and HFREF patients and thus, efficacy assessment of Sacubitril / Valsartan is a clinically meaningful issue in the large subgroup of HFREF patients with diabetes...
October 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27804100/rhabdomyolysis-after-coadministration-of-atorvastatin-and-sacubitril-valsartan-entresto%C3%A2-in-a-63-year-old-woman
#9
Eve S Faber, Madhavi Gavini, Ronald Ramirez, Richard Sadovsky
A 63-year-old woman previously stable on a regimen of atorvastatin 40 mg daily, carvedilol 25 mg twice daily, digoxin 0.125 mg daily, furosemide 40 mg daily, spironolactone 25 mg daily, rivaroxaban 15 mg daily, and enalapril 20 mg twice daily for heart failure developed rhabdomyolysis 26 days after enalapril was stopped and sacubitril/valsartan (Entresto™) started. The patient received sacubitril/valsartan at 24/26 mg twice daily for heart failure; however, after 26 days she developed muscle and skin pain...
December 2016: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27803793/sacubitril-valsartan-in-heart-failure-latest-evidence-and-place-in-therapy
#10
REVIEW
Edgardo Kaplinsky
Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release)...
November 2016: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/27769970/evolving-therapies-for-the-management-of-chronic-and-acute-decompensated-heart-failure
#11
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27766748/chronic-heart-failure-as-a-state-of-reduced-effectiveness-of-the-natriuretic-peptide-system-implications-for-therapy
#12
Javier Díez
Natriuretic peptides (NPs) promote diuresis, natriuresis and vasodilation in early chronic heart failure (CHF), countering renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS) overstimulation. Despite dramatic increases in circulating NP concentrations as CHF progresses, their effects become blunted. Increases in diuresis, natriuresis, and vasodilation after administration of exogenous atrial (ANP) or brain (BNP) natriuretic peptides are attenuated in patients with advanced CHF compared with controls...
October 21, 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27754187/sp-04-2-lcz-696-a-new-paradigm-shift-for-the-treatment-of-heart-failure
#13
ByungSu Yoo
Heart failure (HF) represents a significant healthcare issue because of its ever-increasing prevalence, poor prognosis and complex pathophysiology. The cornerstone of modern drug therapy in chronic HF is the inhibition of neurohormonal activation that plays a crucial role in the pathophysiology of HF development and progression and, more specifically, of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. LCZ696 is a first-in-class, angiotensin receptor NEP inhibitor (ARNI) that consists of a supramolecular complex of a molecule of the ARB valsartan in combination with a molecule of the NEP inhibitor prodrug AHU377 (also known as sacubitril)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27747488/angiotensin-neprilysin-inhibition-as-a-paradigm-for-all
#14
Muthiah Vaduganathan, Akshay S Desai
Composite angiotensin receptor-neprilysin inhibition (ARNi) represents a novel pharmacologic strategy for treatment of heart failure with reduced ejection fraction (HFrEF). In the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial of 8399 subjects with HFrEF, treatment with the ARNi LCZ696 (sacubitril/valsartan) was associated with statistically important reductions in cardiovascular death, all-cause mortality, and the composite of cardiovascular death or heart failure hospitalization in comparison with enalapril...
November 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27725624/a-treatment-approach-for-patients-with-chronic-systolic-heart-failure
#15
Barry H Greenberg
The treatment of heart failure with reduced ejection (HFrEF) is changing rapidly. Advances over the past several decades have focused on blocking the adverse effects of neurohormonal activation. This approach has resulted in marked improvement in outcomes in the HFrEF population. Despite these advances, however, mortality and morbidity remain high and HFrEF patients have poor quality of life. New approaches to therapy now offer additional benefits. Combined neprilysin inhibition and angiotensin receptor blockade using sacubitril-valsartan (LCZ696) has been shown to be superior to an angiotensin-converting enzyme inhibitor in HFrEF patients...
2016: Reviews in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27719743/effect-of-food-on-the-oral-bioavailability-of-the-angiotensin-receptor-neprilysin-inhibitor-sacubitril-valsartan-lcz696-in-healthy-subjects%C3%A2
#16
Surya Ayalasomayajula, Thomas H Langenickel, Priya Chandra, Edward D Wolfson, Diego Albrecht, Wei Zhou, Parasar Pal, Iris Rajman, Gangadhar Sunkara
OBJECTIVE: Sacubitril/valsartan (LCZ696) provides a novel therapeutic approach of neurohormonal modulation in heart failure via simultaneous inhibition of neprilysin and blockade of the angiotensin II type-1 receptor. This study was conducted to evaluate the effect of food on the oral bioavailability of LCZ696 analytes. MATERIALS AND METHODS: This was an open-label, randomized, 3-period crossover study in healthy subjects. Eligible subjects (N = 36) were randomized to 6 treatment sequences, each comprising 3 treatment periods during which subjects received a single oral dose of 400 mg LCZ696 under fasting condition and following a low- and high-fat meal...
December 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27697814/european-drug-market-entries-2015-with-new-mechanisms-of-action
#17
Titus W P van den Heuvel, Adam F Cohen, Robert Rissmann
In this article, we consider the new drugs approved for the European market in 2015. We present a summary of the new mechanisms of action introduced and highlight three new mechanisms of action with a potentially high future impact: PCSK9 inhibition (alirocumab (Praluent®) and evolocumab (Repatha®)) for hypercholesterolaemia, neprilysin inhibition (sacubitril in combination with valsartan (Entresto®)) for heart failure, and interleukin-5 inhibition (mepolizumab (Nucala®)) for asthma.
October 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
https://www.readbyqxmd.com/read/27673415/current-treatment-of-heart-failure-with-reduction-of-left-ventricular-ejection-fraction
#18
Wilbert S Aronow
Heart failure is the commonest cause of hospitalization and of rehospitalization This review paper is a comprehensive review of current treatment of heart failure in 2016. The target of this review is all health care professionals who treat patients with heart failure. Areas covered: This article discusses stages of heart failure, treatment of heart failure with general measures, and drug therapy with diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, aldosterone antagonists, isosorbide dinitrate plus hydralazine, digoxin, other neurohormonal antagonists, sacubitril/valsartan, calcium channel blockers, and ivabradine...
October 11, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27668049/entresto-sacubitril-valsartan-first-in-class-angiotensin-receptor-neprilysin-inhibitor-fda-approved-for-heart-failure
#19
Loretta Fala
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
https://www.readbyqxmd.com/read/27665860/neprilysin-inhibition-a-brief-review-of-past-pharmacological-strategies-for-heart-failure-treatment-and-future-directions
#20
Erik H Howell, Scott J Cameron
Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various "novel" pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF...
September 26, 2016: Cardiology Journal
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