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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
#1
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/28801884/identification-and-partial-structural-characterization-of-mass-isolated-valsartan-and-its-metabolite-with-messenger-tagging-vibrational-spectroscopy
#2
Olga Gorlova, Sean M Colvin, Antonio Brathwaite, Fabian S Menges, Stephanie M Craig, Scott J Miller, Mark A Johnson
Recent advances in the coupling of vibrational spectroscopy with mass spectrometry create new opportunities for the structural characterization of metabolites with great sensitivity. Previous studies have demonstrated this scheme on 300 K ions using very high power free electron lasers in the fingerprint region of the infrared. Here we extend the scope of this approach to a single investigator scale as well as extend the spectral range to include the OH stretching fundamentals. This is accomplished by detecting the IR absorptions in a linear action regime by photodissociation of weakly bound N2 molecules, which are attached to the target ions in a cryogenically cooled, rf ion trap...
August 11, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28800834/benefits-and-harms-of-sacubitril-in-adults-with-heart-failure-and-reduced-left-ventricular-ejection-fraction
#3
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...
July 14, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28793821/the-effects-of-lcz696-in-patients-with-hypertension-compared-with-angiotensin-receptor-blockers-a-meta-analysis-of-randomized-controlled-trials
#4
Yang Zhao, Heng Yu, Xu Zhao, Ruixin Ma, Ningyin Li, Jing Yu
LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, has been demonstrated to have greater advantages in the treatment of heart failure compared with angiotensin-converting enzyme inhibitors, enalapril, or angiotensin receptor blockers (ARBs). However, studies that compared the efficacy and safety of LCZ696 against valsartan in patients with hypertension are limited. To provide further evidence for the benefits of LCZ696 and to make this assessment, a meta-analysis of randomized controlled trials (RCTs) was performed...
September 2017: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28765411/heart-failure-what-s-new-and-what-s-changed
#5
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
#6
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/28721135/a-comprehensive-guidelines-based-approach-reduces-cardiovascular-risk-in-everyday-practice-the-varo-study
#7
Tomáš Štulc, Věra Lánská, Michaela Šnejdrlová, Michal Vrablík, Martina Prusíková, Richard Češka
INTRODUCTION: The aim of study was to investigate the possibility of cardiovascular risk improvement through systematic identification of high-risk individuals and treatment in accordance with current guidelines using modern therapy in daily clinical practice. MATERIAL AND METHODS: Two hundred and sixty-three physicians participated in the study. The physicians were asked to screen for cardiovascular risk factors in patients presenting with unrelated problems and to re-evaluate the attainment of treatment goals in those with already known risk factors...
June 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28720639/angioedema-spotlight-a-closer-examination-of-sacubitril-valsartan-safety-results
#8
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
#9
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/28713936/epigallocatechin-gallate-attenuates-overload%C3%A2-induced-cardiac-ecm-remodeling-via-restoring-t-cell-homeostasis
#10
Yongsheng Han, Qingtong Wang, Xizhen Fan, Jun Chu, Junfu Peng, Yousheng Zhu, Yan Li, Xiaojing Li, Lei Shen, James Asenso, Shanfeng Li
It has previously been demonstrated that Epigallocatechin gallate (EGCG) has regulatory effects on cellular immunity. The present study explored whether EGCG inhibits the overload‑induced cardiac extracellular matrix (ECM) remodeling through targeting the balance of T cell subpopulations. Sprague‑Dawley rats were subjected to either transverse aortic constriction (TAC) or sham operation. TAC rats were treated with EGCG or valsartan (Val) for 6 weeks. The administration of EGCG or Val ameliorated the overproduction of cardiac collagen, inhibited matrix metalloproteinase (MMP) activity, decreased the expression of tissue inhibitor of MMP‑2, atrial natriuretic peptide and brain natriuretic peptide...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28698735/cardioprotection-against-heart-failure-by-shenfu-injection-via-tgf-%C3%AE-smads-signaling-pathway
#11
Jingyu Ni, Yang Shi, Lan Li, Jingrui Chen, Lingyan Li, Min Li, Jinqiang Zhu, Yan Zhu, Guanwei Fan
OBJECTIVE: To explore the potential cardioprotective mechanism of Shenfu injection (SFI) against heart failure (HF) by attenuating myocardial fibrosis and cardiac remodeling. METHODS AND RESULTS: Four weeks after myocardial infarction (MI), adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD) rats were observed to investigate changes in cardiac structure and function...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28690250/simultaneous-determination-of-felodipine-and-metoprolol-in-beagle-dog-plasma-by-online-spe-lc-ms-ms-and-its-application-in-a-pharmacokinetic-study
#12
Meiling Chen, Jiezhao Zhou, Le Mei, Fanglin Yu, Xiangyang Xie, Yan Liu, Yang Yang, Ying Li, Xingguo Mei
In order to overcome deficiencies for simultaneously determining felodipine (FDP) and metoprolol (MPL) with low recovery and low sensitivity, a new online SPE coupled with the liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method for the simultaneous quantitative determination of FDP and MPL in beagle dog plasma was established. The SPE extraction of FDP and MPL was performed on a Retain PEP Javelin column (10 × 2.1 mm, 5 μm), while the chromatographic separation was achieved on a ZORBAX SB-C18 (50 × 2...
2017: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/28689178/sacubitril-valsartan-beyond-natriuretic-peptides
#13
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/28676030/heart-failure-with-preserved-ejection-fraction-a-dilemma-in-treatment-options
#14
Taylor Bramblett, Mohamed Teleb, Aymen Albaghdadi, Harsh Agrawal, Debabrata Mukherjee
Heart failure with preserved ejection fraction (HFpEF) makes up half of diagnosed heart failure cases and has similar outcomes compared to heart failure with reduced ejection fraction (HFrEF) but a discrepancy in knowledge and approach to treatment. HFpEF is diagnosed using the following criteria: symptoms, preserved ejection fraction (greater than 50%), and evidence of abnormal left ventricular filling or relaxation, or diastolic distensibility or stiffness. Studies conducted to examine the efficacy of angiotensin receptor blockers (irbesartan and candesartan), thiazide diuretics (chlorthalidone), and angiotensin converting enzyme inhibitors (perindopril) in the treatment of HFpEF, showed moderate efficacy but no clear benefit...
July 3, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28670240/telmisartan-induced-sprue-like-enteropathy-a-case-report-and-a-review-of-patients-using-non-olmesartan-angiotensin-receptor-blockers
#15
Harshal Surendra Mandavdhare, Vishal Sharma, Kaushal K Prasad, Amit Kumar, Manish Rathi, Surinder S Rana
Recent studies have identified sprue-like illness associated with the use of the antihypertensive agent olmesartan medoxomil. However, whether this condition is specific to the use of olmesartan or is associated with the use of drugs belonging to the class of "sartans" remains to be clarified. A 45-year-old woman with chronic kidney disease along with hypothyroidism and hypertension presented with chronic diarrhea and significant weight loss. Endoscopy of the upper gastrointestinal tract showed scalloping and grooving of the duodenum, and histopathological examination showed subtotal villous atrophy...
July 2017: Intestinal Research
https://www.readbyqxmd.com/read/28666228/high-throughput-quantification-of-8-antihypertensive-drugs-and-active-metabolites-in-human-plasma-using-uplc-ms-ms
#16
Bart C H van der Nagel, Jorie Versmissen, Soma Bahmany, Teun van Gelder, Birgit C P Koch
BACKGROUND: To assess drug adherence of patients with hypertension, an analytical method was developed and validated using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The method includes eight frequently prescribed antihypertensive drugs from four classes and their active metabolites: angiotensin converting enzyme inhibitors enalapril and perindopril (active metabolites respectively enalaprilate and perindoprilate), angiotensin II receptor blockers losartan (with the active metabolite losartan carboxylic acid) and valsartan, calcium channel blockers amlodipine and nifedipine and diuretics hydrochlorothiazide and spironolactone (with the active metabolite canrenone)...
June 19, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28665713/mrna-levels-of-circadian-clock-components-bmal1-and-per2-alter-independently-from-dosing-time-dependent-efficacy-of-combination-treatment-with-valsartan-and-amlodipine-in-spontaneously-hypertensive-rats
#17
Peter Potucek, Michal Radik, Gabriel Doka, Eva Kralova, Peter Krenek, Jan Klimas
Chronopharmacological effects of antihypertensives play a role in the outcome of hypertension therapy. However, studies produce contradictory findings when combination of valsartan plus amlodipine (VA) is applied. Here, we hypothesized different efficacy of morning versus evening dosing of VA in spontaneously hypertensive rats (SHR) and the involvement of circadian clock genes Bmal1 and Per2. We tested the therapy outcome in short-term and also long-term settings. SHRs aged between 8 and 10 weeks were treated with 10 mg/kg of valsartan and 4 mg/kg of amlodipine, either in the morning or in the evening with treatment duration 1 or 6 weeks and compared with parallel placebo groups...
June 30, 2017: Clinical and Experimental Hypertension: CHE
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
#18
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/28658108/effectiveness-and-safety-of-valsartan-amlodipine-in-hypertensive-patients-with-stroke-china-status-ii-subanalysis
#19
MULTICENTER STUDY
Weiliang Zhang, Yongbin Song, Jiangtao Xu
High blood pressure (BP) is a major risk factor associated with stroke in China. This is a subanalysis of patients from the China Status II study, aimed to evaluate the effectiveness and safety of valsartan/amlodipine (Val/Aml) single-pill combination (SPC) in hypertensive patients with different stroke subtypes (hemorrhagic, ischemic, or mixed).China Status II was a multicenter, postmarketing, prospective observational study in hypertensive patients uncontrolled on monotherapy. The study was an 8-week open-label treatment period with 2 4-week follow-ups...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28653148/-new-pharmacologic-therapies-for-chronic-heart-failure
#20
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
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