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sacubitril, valsartan

Lourdes Vicent, Alberto Esteban-Fernández, Manuel Gómez-Bueno, Javier De-Juan, Pablo Díez-Villanueva, Ángel Manuel Iniesta, Ana Ayesta, Hugo González-Saldívar, Antonio Rojas-González, Ramón Bover-Freire, Diego Iglesias, Marcos García-Aguado, Jesús A Perea-Egido, Manuel Martínez-Sellés
Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice.We performed a multicenter registry in 10 hospitals. All patients who started SV from October 2016 to March 2017 on an outpatient basis were included.A total of 427 patients started treatment with SV. Mean follow-up was 7.0±0.1 months. Forty-nine patients (11.5%) discontinued SV, and 12 (2.8%) died. SV discontinuation was associated with higher cardiovascular (hazard ratio [HR] 13...
December 10, 2018: Journal of Cardiovascular Pharmacology
Amy X Du, Cynthia M Westerhout, Finlay A McAlister, Miriam Shanks, Gavin Y Oudit, D Ian Paterson, Mikael Hanninen, Jissy Thomas, Justin A Ezekowitz
Little is known about the dosing and tolerability of sacubitril/valsartan (LCZ696; Entresto™, Quebec, Canada) in a non-clinical trial population. This study was conducted to evaluate the use and tolerability of sacubitril/valsartan in patients followed at a multidisciplinary heart failure clinic. We performed a retrospective chart review of 126 patients with heart failure, initiated on sacubitril/valsartan, and seen at a specialty heart failure clinic between August 1, 2015 and August 1, 2017. We defined the target dose of sacubitril/valsartan as 200 mg B...
December 10, 2018: Journal of Cardiovascular Pharmacology
Yong Huo, Weimin Li, Randy Webb, Li Zhao, Qian Wang, Weinong Guo
This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild-to-moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild-to-moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8...
December 11, 2018: Journal of Clinical Hypertension
Joanna Osmanska, Pardeep S Jhund
The foundation of the treatment of heart failure with reduced ejection fraction is a number of pharmacotherapies shown to reduce morbidity and mortality in large randomised multinational clinical trials. These include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, and more recently, a combined angiotensin receptor blocker neprilysin inhibitor, sacubitril/valsartan. In select cases, digoxin, ivabradine and hydralazine with isosorbide dinitrate have a role to play in the treatment of heart failure with reduced ejection fraction...
December 11, 2018: Drugs & Aging
Francisco J Pastor-Pérez, Arcadio García-Alberola, Marina Navarro-Peñalver, Rebeca Goya-Esteban, Iris P Garrido-Bravo, Oscar Barquero-Pérez, Jose Luis Rojo-Álvarez, Domingo A Pascual-Figal
Autonomic regulation plays a role in the progression of heart failure with reduced ejection fraction (HrEF).Twenty-one HFrEF patients, 60.8 ± 13.1 years, receiving angiotensin inhibition, were replaced by angiotensin receptor-neprilysin inhibitor (ARNI). A 24-hour Holter recording was performed before and after 3 months of the maximum tolerated dose of ARNi. We evaluated changes in autonomic tone using heart rate variability (SDNN, rMSSD, pNN50, LF, HF, LF/HF, α1, α2), and heart rate turbulence (TO and TS)...
November 28, 2018: Journal of Electrocardiology
Sercan Okutucu, Cengiz Sabanoglu, Begum Yetis Sayin, Hakan Aksoy, Nurbanu Bursa, Ali Oto
BACKGROUND: Angiotensin receptor neprilysin inhibitor (ARNI, sacubitril/valsartan) reduces sudden death in heart failure with reduced ejection fraction (HFrEF). Corrected QT (QTc), T-wave peak to T-wave end interval (Tp-e) and Tp-e/QTc are electrocardiographic indices of ventricular repolarization heterogeneity. We aimed to assess the effects of switching from ramipril to ARNI on electrocardiographic indices of ventricular repolarization. METHODS: A total of 48 patients with HFrEF (mean age: 63...
December 4, 2018: Acta Cardiologica
Pierre Vladimir Ennezat, Thierry Le Jemtel, Shona Cosgrove, Jesper Hallas, Morten Rix Hansen
BACKGROUND: The impact of randomised controlled trials (RCTs) depends heavily on the presentation of the findings. OBJECTIVE: Classically, RCT findings are presented in the form of absolute risk reduction (ARR), number needed to treat (NNT) to prevent one adverse outcome, and relative risk reduction (RRR) or hazard ratio (the most favourable means for drug marketing). However, the estimation of average survival gain (i.e. outcome postponement between a trial intervention and comparator) is an alternative and informative means of presenting the findings of RCTs...
December 4, 2018: Acta Cardiologica
Jonathan P Mochel, Chi Hse Teng, Mathieu Peyrou, Jerome Giraudel, Meindert Danhof, Dean F Rigel
Simultaneous blockade of angiotensin receptors and enhancement of natriuretic peptides (NP) by the first-in-class angiotensin receptor neprilysin (NEP) inhibitor sacubitril/valsartan constitutes an effective approach to treating heart failure. This study examined the effects of sacubitril/valsartan (225 and 675 mg/day) vs. placebo, sacubitril (360 mg/day), valsartan (900 mg/day), and benazepril (5 mg/day) on the dynamics of the renin-angiotensin-aldosterone system (RAAS) and the NP system in dogs. Beagle dogs (n = 18) were fed a low-salt diet (0...
November 30, 2018: European Journal of Pharmaceutical Sciences
Pratyaksh K Srivastava, Brian L Claggett, Scott D Solomon, John J V McMurray, Milton Packer, Michael R Zile, Akshay S Desai, Jean L Rouleau, Karl Swedberg, Gregg C Fonarow
Importance: The addition of neprilysin inhibition to standard therapy, including a renin-angiotensin system blocker, has been demonstrated to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) compared with standard therapy alone. The long-term absolute risk reduction from angiotensin receptor neprilysin inhibitor (ARNI) therapy, and whether it merits widespread use among diverse subpopulations, has not been well described. Objective: To calculate estimated 5-year number needed to treat (NNT) values overall and for different subpopulations for the Prospective Comparison of ARNI with Angiotensin-Converting Enzyme Inhibitor (ACEI) to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) cohort...
November 28, 2018: JAMA Cardiology
Kelsie E Oatmen, Michael R Zile, John C Burnett, Francis G Spinale
Importance: The standard pharmacotherapy for heart failure (HF), particularly HF with reduced ejection fraction (HFrEF), is primarily through the use of receptor antagonists, notably inhibition of the renin-angiotensin system by either angiotensin-converting enzyme inhibition or angiotensin II receptor blockade (ARB). However, the completed Prospective Comparison of ARNI With an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial identified that the use of a single molecule (sacubitril/valsartan), which is an ARB and the neutral endopeptidase inhibitor (NEPi) neprilysin, yielded improved clinical outcomes in HFrEF compared with angiotensin-converting enzyme inhibition alone...
November 28, 2018: JAMA Cardiology
Alexandra Le Bras
No abstract text is available yet for this article.
November 27, 2018: Nature Reviews. Cardiology
Chirik Wah Lau, Pieter Martens, Seppe Lambeets, Matthias Dupont, Wilfried Mullens
BACKGROUND: Sacubitril/valsartan significantly reduced heart failure(HF) hospitalisations and mortality in the PARADIGM-HF-trial. However real-world data on symptomatic and functional improvement are lacking. METHODS: Between December 2016 and January 2018, we retrospectively collected baseline and follow-up data including New York Heart Association (NYHA)-functional class and Cardio-pulmonary exercise data(CPET) in all HF-patients receiving sacubitril/valsartan...
November 25, 2018: Acta Cardiologica
Mikhail Y Maslov, Stephan Foianini, Dita Mayer, Michael V Orlov, Mark A Lovich
BACKGROUND: Simultaneous neprilysin inhibition (NEPi) and angiotensin receptor blockade (ARB) with sacubitril/valsartan improves cardiac function and exercise tolerance in patients with heart failure (HF). However, it is not known if these therapeutic benefits are primarily due to NEPi with sacubitril or ARB with valsartan, or their combination. Therefore, the aim of this study was to investigate the potential contribution of sacubitril and valsartan to the benefits of the combination therapy on left ventricular (LV) function and exercise tolerance...
November 21, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Jaromír Hradec
Pharmacotherapy of chronic heart failure with reduced ejection fraction (HFrEF) is based on convincing evidence of both, the efficacy and the safety of drugs we are using. This evidence was obtained in big and carefully controlled randomised morbidity/mortality trials; therefore we are talking about evidence-based medicine. The basis for the pharmacological treatment is inhibition of pathologically long-term activated neurohumoral systems, mainly of the sympatoadrenal one by betablockers as well as of the renin-angiotensin-aldosterone one by ACE inhibitors/sartans and by mineralocorticoid receptor antagonists...
2018: Vnitr̆ní Lékar̆ství
Antoni Bayes-Genis
The European Society of Cardiology guidelines for the diagnosis and treatment of heart failure (HF) was updated in 2016. In this article, highlights of the updates made based on new findings and practical recommendations are presented. The 2016 guidelines include definitions and criteria for diagnosing the different types of HF. In addition, a newly developed algorithm is proposed for treating particularly symptomatic HF with reduced ejection fraction, including the use of the angiotensin-converting enzyme inhibitors, beta-blockers, mineralocorticoid receptor antagonists and the angiotensin receptor neprilysin inhibitor sacubitril/valsartan...
December 2017: European Cardiology
Eric J Velazquez, David A Morrow, Adam D DeVore, Carol I Duffy, Andrew P Ambrosy, Kevin McCague, Ricardo Rocha, Eugene Braunwald
BACKGROUND: Acute decompensated heart failure accounts for more than 1 million hospitalizations in the United States annually. Whether the initiation of sacubitril-valsartan therapy is safe and effective among patients who are hospitalized for acute decompensated heart failure is unknown. METHODS: We enrolled patients with heart failure with reduced ejection fraction who were hospitalized for acute decompensated heart failure at 129 sites in the United States. After hemodynamic stabilization, patients were randomly assigned to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or enalapril (target dose, 10 mg twice daily)...
November 11, 2018: New England Journal of Medicine
Juan Torrado, Chad Cain, Adolfo G Mauro, Francisco Romeo, Ramzi Ockaili, Vinh Q Chau, John A Nestler, Teja Devarakonda, Siddhartha Ghosh, Anindita Das, Fadi N Salloum
BACKGROUND: Sacubitril/valsartan (SAC/VAL) is approved by the U.S. Food and Drug Administration for heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study investigated the effects of SAC/VAL on acute myocardial infarction (MI) and cardiac remodeling in a translational rabbit model of MI. METHODS: New Zealand White rabbits were sedated and underwent conscious MI (45-min ischemia) by balloon inflation (previously implanted surgically) followed by 72 h (acute protocol) or 10 weeks (chronic protocols) of reperfusion...
November 6, 2018: Journal of the American College of Cardiology
M V Zhuravleva, A B Prokofiev, E V Shih, S Y Serebrova, G I Gorodetskaya
In this article we have described clinical pharmacology and data of clinical studies of an innovational drug valsartan + sacubitril in patients with chronic heart failure (CHF). The use of supramolecular complex valsartan + sacubitril allows to elevate quality of life and improve prognosis of patients with CHF. High efficacy of valsartan+sacubitril relative to impact on composite primary end-point (cardiovascular death + hospitalization due to CHF) was demonstrated in the clinical trial PARADIGM-HF in which it was compared with angiotensin converting enzyme inhibitor enalapril...
October 2018: Kardiologiia
Axel Sarrias, Antoni Bayes-Genis
No abstract text is available yet for this article.
August 7, 2018: Circulation
James L Januzzi, Milton Packer, Brian Claggett, Jiankang Liu, Amil M Shah, Michael R Zile, Burkert Pieske, Adriaan Voors, Parul U Gandhi, Margaret F Prescott, Victor Shi, Martin P Lefkowitz, John J V McMurray, Scott D Solomon
BACKGROUND: Increased activity of IGFBP7 (insulin-like growth factor-binding protein-7) is associated with cellular senescence, tissue aging, and obesity. IGFBP7 may be related to heart failure with preserved ejection fraction, a disease of elderly obese people. METHODS AND RESULTS: In a subset of patients with heart failure with preserved ejection fraction (N=228) randomized to receive sacubitril/valsartan versus valsartan, IGFBP7 concentrations were measured at baseline, 12 weeks, and 36 weeks...
October 2018: Circulation. Heart Failure
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