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Sacubitril/valsartan

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https://www.readbyqxmd.com/read/28737127/pharmacokinetics-and-safety-of-sacubitril-valsartan-lcz696-in-patients-with-mild-and-moderate-hepatic-impairment%C3%A2
#1
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...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28720639/angioedema-spotlight-a-closer-examination-of-sacubitril-valsartan-safety-results
#2
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
#3
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/28689178/sacubitril-valsartan-beyond-natriuretic-peptides
#4
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...
July 8, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28662936/angiotensin-receptor-neprilysin-inhibition%C3%A2-in-heart-failure-with-preserved%C3%A2-ejection-fraction-rationale-and-design-of-the-paragon-hf-trial
#5
REVIEW
Scott D Solomon, Adel R Rizkala, Jianjian Gong, Wenyan Wang, Inder S Anand, Junbo Ge, Carolyn S P Lam, Aldo P Maggioni, Felipe Martinez, Milton Packer, Marc A Pfeffer, Burkert Pieske, Margaret M Redfield, Jean L Rouleau, Dirk J Van Veldhuisen, Faiez Zannad, Michael R Zile, Akshay S Desai, Victor C Shi, Martin P Lefkowitz, John J V McMurray
OBJECTIVES: The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) trial is designed to determine the efficacy and safety of the angiotensin receptor neprilysin inhibitor sacubitril/valsartan compared with valsartan in patients with chronic heart failure and preserved ejection fraction (HFpEF). BACKGROUND: HFpEF is highly prevalent, associated with substantial morbidity and mortality, and in need of effective therapies that improve outcomes...
July 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28653148/-new-pharmacologic-therapies-for-chronic-heart-failure
#6
REVIEW
T Kempf, U Bavendiek, J Bauersachs
Heart failure is a disease with a high prevalence and incidence. New therapeutic approaches are needed to prevent the onset of heart failure and to reduce the high morbidity and mortality associated with this disease. An optimized therapy of arterial hypertension in patients with risk factors and the use of the SGLT2 inhibitor empagliflozin in type 2 diabetics are proven strategies to prevent heart failure. The therapeutic options in heart failure with preserved ejection fraction are still insufficient. In heart failure with reduced ejection fraction sacubitril/valsartan, the first approved angiotensin receptor-neprilysin inhibitor, is superior to an angiotensin converting enzyme (ACE) inhibitor...
June 26, 2017: Der Internist
https://www.readbyqxmd.com/read/28652105/pharmacokinetic-pharmacodynamic-and-antihypertensive-effects-of-the-neprilysin-inhibitor-lcz-696-sacubitril-valsartan
#7
REVIEW
Steven G Chrysant
LCZ-696, sacubitril/valsartan, is a dual-acting molecule consisting of the angiotensin II (Ang II) receptor blocker valsartan and the neprilysin (neutral endopeptidase) inhibitor AHU-377 with significant beneficial effects in patients with hypertension and heart failure (HF). Several recent studies have demonstrated a higher effectiveness of LCZ-696 compared to valsartan in the treatment of hypertension and HF. The rationale for the development and the Food and Drug Administration approval of LCZ-696 was based on the concept of an additive effect of the Ang II receptor blocker valsartan and the neutral endopeptidase (neprilysin) inhibitor AHU-377 for the treatment of hypertension and HF...
May 25, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28649439/mechanisms-of-action-of-sacubitril-valsartan-on-cardiac-remodeling-a-systems-biology-approach
#8
Oriol Iborra-Egea, Carolina Gálvez-Montón, Santiago Roura, Isaac Perea-Gil, Cristina Prat-Vidal, Carolina Soler-Botija, Antoni Bayes-Genis
Sacubitril/Valsartan, proved superiority over other conventional heart failure management treatments, but its mechanisms of action remains obscure. In this study, we sought to explore the mechanistic details for Sacubitril/Valsartan in heart failure and post-myocardial infarction remodeling, using an in silico, systems biology approach. Myocardial transcriptome obtained in response to myocardial infarction in swine was analyzed to address post-infarction ventricular remodeling. Swine transcriptome hits were mapped to their human equivalents using Reciprocal Best (blast) Hits, Gene Name Correspondence, and InParanoid database...
2017: NPJ Systems Biology and Applications
https://www.readbyqxmd.com/read/28648033/-update-on-the-clinical-application-of-valsartan-sacubitril-in-patients-with-heart-failure
#9
(no author information available yet)
No abstract text is available yet for this article.
June 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28644179/improving-heart-failure-patient-outcomes-utilizing-guideline-directed-therapy
#10
Beth Towery Davidson, Terri Lynn Allison
Heart failure (HF) prevalence continues to rise and remains a significant burden to patients, caregivers, providers, and the healthcare system. Guideline-directed medical therapy with standard neurohormonal blockade has been the cornerstone of medical management for many years. Despite aggressive utilization of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and aldosterone antagonists, HF hospitalizations and readmissions are common and residual mortality remains high...
July 21, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28643522/should-all-heart-failure-patients-be-treated-with-sacubitril-valsartan
#11
Robert P Blankfield
No abstract text is available yet for this article.
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28614052/safety-of-the-neprilysin-renin-angiotensin-system-inhibitor-lcz696
#12
REVIEW
Bo Li, Yunhe Zhao, Bo Yin, Mengfei Helian, Xinmei Wang, Feng Chen, Hongxia Zhang, Hui Sun, Bin Meng, Fengshuang An
OBJECTIVES: The combined neprilysin/rennin-angiotensin system inhibitor sacubitril/valsartan (LCZ696) has shown its superiority over ACEI/ARB therapy. In view of the existing concern of its adverse effects, we aimed to provide evidence of the safety of the new drug. RESULTS: A total of 6 randomized trials with 11,821 subjects were included in this analysis. No significant differences were found in any adverse effects between LCZ696 and ACEI/ARB or placebo groups...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28602366/treatment-of-heart-failure-with-abnormal-left-ventricular-systolic-function-in-older-adults
#13
REVIEW
Wilbert S Aronow
Heart failure (HF) with abnormal left ventricular (LV) ejection fraction should be identified and treated. Treat hypertension with diuretics, angiotensin-converting enzyme (ACE) inhibitors, and β-blockers. Treat myocardial ischemia with nitrates and β-blockers. Treat volume overload and HF with diuretics. Treat HF with ACE inhibitors and β-blockers. Sacubitril/valsartan may be used instead of an ACE inhibitor or ARB in chronic symptomatic HF and abnormal LV ejection fraction. Add isosorbide dinitrate/hydralazine in African Americans with class II to IV HF treated with diuretics, ACE inhibitors, and β-blockers...
July 2017: Heart Failure Clinics
https://www.readbyqxmd.com/read/28601914/left-ventricular-ejection-fraction-as-therapeutic-target-is-it-the-ideal-marker
#14
REVIEW
V Katsi, G Georgiopoulos, A Laina, E Koutli, J Parissis, C Tsioufis, P Nihoyannopoulos, D Tousoulis
Heart failure (HF) consists the fastest growing clinical cardiac disease. HF patients are categorized on the basis of underlying left ventricular ejection fraction (LVEF) into HF with preserved EF (HFpEF), reduced LVEF (HFrEF), and mid-range LVEF (HFmrEF). While LVEF is the most commonly used surrogate marker of left ventricular (LV) systolic function, the implementation of two-dimensional echocardiography in estimating this parameter imposes certain caveats on current HF classification. Most importantly, LVEF could fluctuate in repeated measurements or even recover after treatment, thus blunting the borders between proposed categories of HF and enabling upward classification of patients...
June 10, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28599060/evaluation-of-pharmacokinetic-and-pharmacodynamic-drug-drug-interaction-of-sacubitril-valsartan-lcz696-and-sildenafil-in-patients-with-mild-to-moderate-hypertension
#15
Hsiu-Ling Hsiao, Thomas H Langenickel, Jesika Petruck, Kiran Kode, Surya Ayalasomayajula, Uwe Schuehly, Michael Greeley, Parasar Pal, Wei Zhou, Margaret F Prescott, Gangadhar Sunkara, Iris Rajman
Sacubitril/valsartan (LCZ696) is indicated for the treatment of patients with heart failure and reduced ejection fraction (HFrEF). Since patients with HFrEF may receive sacubitril/valsartan and sildenafil, both increasing cGMP, the present study evaluated the pharmacokinetic and pharmacodynamic drug interaction potential between sacubitril/valsartan and sildenafil. In this open-label, 3-period, single sequence study, patients with mild-to-moderate hypertension (153.8±8.2 mm Hg mean SBP) received a single dose of sildenafil 50 mg, sacubitril/valsartan 400 mg once daily for 5 days, and sacubitril/valsartan and sildenafil co-administration...
June 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28587583/angiotensin-receptor-neprilysin-inhibition
#16
Ofer Havakuk, Uri Elkayam
The novel combination sacubitril/valsartan represents a new therapeutic approach in the management of heart failure. With the simultaneous blockage of the enzyme neprilysin (by sacubitril) and angiotensin II receptors (by valsartan), this combination reduces the degradation of natriuretic peptides and other counterregulatory peptide systems while avoiding the deleterious effect of angiotensin II receptors activation and thereby encompasses a beneficial impact of 2 important neurohormonal pathways activated in heart failure...
July 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28577679/the-effects-of-sacubitril-valsartan-on-coronary-outcomes-in-paradigm-hf
#17
Ulrik M Mogensen, Lars Køber, Søren L Kristensen, Pardeep S Jhund, Jianjian Gong, Martin P Lefkowitz, Adel R Rizkala, Jean L Rouleau, Victor C Shi, Karl Swedberg, Michael R Zile, Scott D Solomon, Milton Packer, John J V McMurray
BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-I), are beneficial both in heart failure with reduced ejection fraction (HF-REF) and after myocardial infarction (MI). We examined the effects of the angiotensin-receptor neprilysin inhibitor sacubitril/valsartan, compared with the ACE-I enalapril, on coronary outcomes in PARADIGM-HF. METHODS AND RESULTS: We examined the effect of sacubitril/valsartan compared with enalapril on the following outcomes: i) the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, ii) a pre-defined broader composite including, in addition, MI, stroke, and resuscitated sudden death, and iii) a post hoc coronary composite of CV-death, non-fatal MI, angina hospitalization or coronary revascularization...
June 2017: American Heart Journal
https://www.readbyqxmd.com/read/28571599/patients-not-meeting-paradigm-hf-enrollment-criteria-are-eligible-for-sacubitril-valsartan-on-the-basis-of-fda%C3%A2-approval-the-need-to-close-the-gap
#18
REVIEW
Antonio L Perez, Veraprapas Kittipibul, W H Wilson Tang, Randall C Starling
No abstract text is available yet for this article.
June 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/28569442/first-derivative-emission-spectrofluorimetric-method-for-the-determination-of-lcz696-a-newly-approved-fda-supramolecular-complex-of-valsartan-and-sacubitril-in-tablets
#19
Marwa A A Ragab, Shereen M Galal, Mohamed A Korany, Aya R Ahmed
LCZ696 (sacubitril/valsartan, Entresto™) is a therapy lately approved by United States Food and Drug Administration (US FDA) as a heart failure therapy. It is claimed to decrease the mortality rate and hospitalization for patients with chronic heart failure. This study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions that may affect its fluorescence. Various conditions were studied, for example studying the effects of organized media, solvents and pH, which may affect the fluorescence behavior of sacubitril...
June 1, 2017: Luminescence: the Journal of Biological and Chemical Luminescence
https://www.readbyqxmd.com/read/28537000/advances-in-clinical-cardiology-2016-a-summary-of-the-key-clinical-trials
#20
REVIEW
Alastair Gray, Conor McQuillan, Ian B A Menown
INTRODUCTION: The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. METHODS: The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA)...
May 23, 2017: Advances in Therapy
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