Sacubitril/valsartan: from a large clinical trial to clinical practice
The Prospective Comparison of Angiotensin Receptor Antagonist and Neprilysin Inhibitor with Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) has shown a reduction in the risk of death and heart failure hospitalizations with sacubitril/valsartan, compared with enalapril, in patients with heart failure and reduced ejection fraction. Guidelines now recommend the substitution of angiotensin-converting enzyme inhibitors or AT1 blockers with sacubitril/valsartan in patients with heart failure and reduced ejection fraction. The aim of this review is...
Source: Journal of Cardiovascular Medicine - July 31, 2018 Category: Cardiology Tags: Review Source Type: research

RE: Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction.
Authors: Cristino J, Tang I, Ng C, Tan J, Trueman D, Lee D PMID: 30033833 [PubMed - as supplied by publisher] (Source: Journal of Medical Economics)
Source: Journal of Medical Economics - July 25, 2018 Category: Health Management Tags: J Med Econ Source Type: research

Nandrolone alter left ventricular contractility and promotes remodelling involving calcium-handling proteins and renin-angiotensin system in male SHR
Publication date: Available online 21 July 2018Source: Life SciencesAuthor(s): Antonio F. Melo Junior, Polyana L.M. Dalpiaz, Glauciene J. Sousa, Phablo Wendell C. Oliveira, Antônio M. Birocale, Tadeu U. Andrade, Gláucia R. Abreu, Nazaré S. BissoliAbstractAimsHypertension is a highly prevalent disease that has been correlated to severe organ damage and mortality. However, the role of androgens in hypertension is controversial. The aim of this study was to evaluate the cardiac effects of the nandrolone decanoate (NDL) in male SHR.Main methodsAt 12 weeks of age, male SHR rats were separated into three gr...
Source: Life Sciences - July 22, 2018 Category: Biology Source Type: research

From 'fixed dose combinations' to 'a dynamic dose combiner': 3D printed bi-layer antihypertensive tablets.
Abstract There is an increased evidence for treating hypertension by a combination of two or more drugs. Increasing the number of daily intake of tablets has been reported to negatively affect the compliance by patients. Therefore, numerous fixed dose combinations (FDCs) have been introduced to the market. However, the inherent rigid nature of FDCs does not allow titration of the dose of each single component for individual patient needs. In this work, flexible dose combinations of two anti-hypertensive drugs in a single bilayer tablet with a range of doses were fabricated using dual fused deposition modelling (FD...
Source: European Journal of Pharmaceutical Sciences - July 21, 2018 Category: Drugs & Pharmacology Authors: Sadia M, Isreb A, Abbadi I, Isreb M, Aziz D, Selo A, Timmins P, Alhnan MA Tags: Eur J Pharm Sci Source Type: research

Chemoprevention with enalapril and aspirin in Men1(+/T) knockout mouse model
Pancreatic neuroendocrine neoplasias (pNEN) are the most common cause of death in adult patients with multiple endocrine neoplasia type 1 (MEN1). So far, only few chemopreventive strategies (e.g. with somatostatin analogues) have been evaluated for MEN1 associated pNENs. In this experimental study on 75 Men1(+ /T) knockout mice, the effect of aspirin (n=25) and an inhibitor of angiotensin-I converting enzyme (enalapril, n=25) compared to controls (n=25) were evaluated as single chemopreventive strategies for pNENs after 6,9,12,15 and 18 months. After each study period, mice were sacrificed and the resected pancreata were e...
Source: Neuroendocrinology - July 20, 2018 Category: Endocrinology Source Type: research

Cells of ng2 lineage increase in glomeruli of mice following podocyte depletion.
CELLS OF NG2 LINEAGE INCREASE IN GLOMERULI OF MICE FOLLOWING PODOCYTE DEPLETION. Am J Physiol Renal Physiol. 2018 Jul 18;: Authors: Suzuki T, Eng DG, McClelland AD, Pippin JW, Shankland SJ Abstract Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because Neural/glial antigen 2 (NG2) expressing cells can serve as progenitors in other organs, and because herein we showed increased NG2 staining in podocytes following their loss in experimental FSGS, we used l...
Source: American Journal of Physiology. Renal Physiology - July 18, 2018 Category: Physiology Authors: Suzuki T, Eng DG, McClelland AD, Pippin JW, Shankland SJ Tags: Am J Physiol Renal Physiol Source Type: research

Pharmacological Treatment of Arterial Hypertension in Children and AdolescentsNovelty and Significance [Childhood Blood Pressures]
Pharmacological treatment is indicated in children and adolescents with hypertension unresponsive to lifestyle modifications, but there is not enough evidence to recommend 1 class of antihypertensive drugs over others. We performed a network meta-analysis to compare the results of available randomized clinical trials on pharmacological treatment of pediatric hypertension. From a total of 554 potentially relevant studies, 13 randomized placebo-controlled clinical trials enrolling ≥50 patients and a follow-up ≥4 weeks were included. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) after treatment w...
Source: Hypertension - July 11, 2018 Category: Cardiology Authors: Jacopo Burrello, Elvira M. Erhardt, Gaelle Saint–Hilary, Franco Veglio, Franco Rabbia, Paolo Mulatero, Silvia Monticone, Fabrizio D’Ascenzo Tags: Hypertension Original Articles Source Type: research

Does Obstructive Sleep Apnea Influence Blood Pressure and Arterial Stiffness in Response to Antihypertensive Treatment?Novelty and Significance [Obstructive Sleep Apnea]
In this study, we recruited hypertensive patients who underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and carotid-femoral pulse wave velocity. All the examinations except for polysomnography were repeated at 6 and 18 months of follow-up. We studied 94 hypertensive patients (mean age, 55±9 years). The frequency of OSA was 55%. Compared with baseline, we did not observe significant differences between groups in 24-hour BP, daytime systolic a...
Source: Hypertension - July 11, 2018 Category: Cardiology Authors: Fernanda Fatureto–Borges, Raimundo Jenner, Valeria Costa–Hong, Heno F. Lopes, Sandra H. Teixeira, Elias Marum, Dante A.M. Giorgi, Fernanda M. Consolim–Colombo, Luiz A. Bortolotto, Geraldo Lorenzi–Filho, Eduardo M. Krieger, Luciano Tags: Hypertension Original Articles Source Type: research

Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial
Publication date: July 2018Source: The Lancet Diabetes & Endocrinology, Volume 6, Issue 7Author(s): Milton Packer, Brian Claggett, Martin P Lefkowitz, John J V McMurray, Jean L Rouleau, Scott D Solomon, Michael R ZileSummaryBackgroundNeprilysin inhibition has favourable effects on experimental diabetic nephropathy. We sought to assess the effects of neprilysin inhibition on the course of renal function in patients with type 2 diabetes.MethodsIn the randomised, double-blind PARADIGM-HF trial, the effects of sacubitril/valsartan (97 mg/103 mg twice daily) were compared with enalapril (10 mg twice daily) in 8399 patients ...
Source: The Lancet Diabetes and Endocrinology - July 10, 2018 Category: Endocrinology Source Type: research

Renin angiotensin-aldosterone system (RAAS) blockers usage among type II diabetes mellitus patients—A Retrospective Study
ConclusionRAAS blockers usage among T2DM patients was higher in primary care versus tertiary care settings. Majority of the patients did not receive optimal dose of RAAS blockers. (Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews)
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - July 10, 2018 Category: Endocrinology Source Type: research

Diuretic herb Gomphrena celosioides Mart. (Amaranthaceae) promotes sustained arterial pressure reduction and protection from cardiac remodeling on rats with renovascular hypertension
ConclusionsThe G. celosioides diuretic effect is maintained on renovascular hypertensive rats and can reduce the blood pressure after the first week of treatment by inhibiting ACE and these effects are longstanding and strong enough to promote protection against cardiac remodeling. Therefore, it shows potential as an antihypertensive drug.Graphical abstract (Source: Journal of Ethnopharmacology)
Source: Journal of Ethnopharmacology - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats
ConclusionsA 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells.Graphical abstract (Source: Phytomedicine)
Source: Phytomedicine - July 10, 2018 Category: Drugs & Pharmacology Source Type: research

Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure
Publication date: June 2018Source: JACC: Heart Failure, Volume 6, Issue 6Author(s): Kevin Damman, Mauro Gori, Brian Claggett, Pardeep S. Jhund, Michele Senni, Martin P. Lefkowitz, Margaret F. Prescott, Victor C. Shi, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, Milton Packer, Akshay S. Desai, Scott D. Solomon, John J.V. McMurrayAbstractObjectivesThe purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction.BackgroundRenal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate fur...
Source: JACC: Heart Failure - July 10, 2018 Category: Cardiology Source Type: research

Heart failure and inhibition of renin–angiotensin–aldosterone system
Publication date: June 2018Source: Cor et Vasa, Volume 60, Issue 3Author(s): Jiří Vítovec, Jindřich Špinar, Lenka ŠpinarováAbstractA historical survey is presented of mortality clinical trials focussed on the inhibition of the renin–angiotensin–aldosterone system on different levels in patients with chronic heart failure. The first study, CONSENSUS, was published in 1987 and showed that the ACE-inhibitor enalapril clearly reduced mortality in severe heart failure compared with placebo. This was followed by studies with beta blockers, angiotensin II type 1 receptor blockers, ...
Source: Cor et Vasa - July 10, 2018 Category: Cardiology Source Type: research

Arrhythmogenic cardiomyopathy of left ventricle. A rare event, but possible
Publication date: Available online 23 October 2017Source: Cor et VasaAuthor(s): Michele Scarano, Germana Gizzi, Cesare MantiniAbstractArrhythmogenic right ventricular dysplasia (ARVD) is a form of inherited cardiomyopathy characterized by fibro-fatty substitution mainly right ventricular (RV). Affected patients may succumb to life-threatening ventricular arrhythmias and heart failure. It is even more common among athletes who experience sudden cardiac death (SCD). The disease involvement is not limited only to the RV, but the left ventricle (LV) can also be involved. We have reported a case of a 38 years-old man, with two ...
Source: Cor et Vasa - July 10, 2018 Category: Cardiology Source Type: research

Diuretic herb Gomphrena celosioides Mart. (Amaranthaceae) promotes sustained arterial pressure reduction and protection from cardiac remodeling on rats with renovascular hypertension
ConclusionsThe G. celosioides diuretic effect is maintained on renovascular hypertensive rats and can reduce the blood pressure after the first week of treatment by inhibiting ACE and these effects are longstanding and strong enough to promote protection against cardiac remodeling. Therefore, it shows potential as an antihypertensive drug.Graphical abstract (Source: Journal of Ethnopharmacology)
Source: Journal of Ethnopharmacology - July 6, 2018 Category: Drugs & Pharmacology Source Type: research

Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial
Publication date: July 2018Source: The Lancet Diabetes & Endocrinology, Volume 6, Issue 7Author(s): Milton Packer, Brian Claggett, Martin P Lefkowitz, John J V McMurray, Jean L Rouleau, Scott D Solomon, Michael R ZileSummaryBackgroundNeprilysin inhibition has favourable effects on experimental diabetic nephropathy. We sought to assess the effects of neprilysin inhibition on the course of renal function in patients with type 2 diabetes.MethodsIn the randomised, double-blind PARADIGM-HF trial, the effects of sacubitril/valsartan (97 mg/103 mg twice daily) were compared with enalapril (10 mg twice daily) in 8399 patients ...
Source: The Lancet Diabetes and Endocrinology - July 5, 2018 Category: Endocrinology Source Type: research

Renin angiotensin-aldosterone system (RAAS) blockers usage among type II diabetes mellitus patients—A Retrospective Study
ConclusionRAAS blockers usage among T2DM patients was higher in primary care versus tertiary care settings. Majority of the patients did not receive optimal dose of RAAS blockers. (Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews)
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - July 5, 2018 Category: Endocrinology Source Type: research

Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats
ConclusionsA 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells.Graphical abstract (Source: Phytomedicine)
Source: Phytomedicine - July 5, 2018 Category: Drugs & Pharmacology Source Type: research

Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure
Publication date: June 2018Source: JACC: Heart Failure, Volume 6, Issue 6Author(s): Kevin Damman, Mauro Gori, Brian Claggett, Pardeep S. Jhund, Michele Senni, Martin P. Lefkowitz, Margaret F. Prescott, Victor C. Shi, Jean L. Rouleau, Karl Swedberg, Michael R. Zile, Milton Packer, Akshay S. Desai, Scott D. Solomon, John J.V. McMurrayAbstractObjectivesThe purpose of this study was to evaluate the renal effects of sacubitril/valsartan in patients with heart failure and reduced ejection fraction.BackgroundRenal function is frequently impaired in patients with heart failure with reduced ejection fraction and may deteriorate fur...
Source: JACC: Heart Failure - July 5, 2018 Category: Cardiology Source Type: research

Heart failure and inhibition of renin–angiotensin–aldosterone system
Publication date: June 2018Source: Cor et Vasa, Volume 60, Issue 3Author(s): Jiří Vítovec, Jindřich Špinar, Lenka ŠpinarováAbstractA historical survey is presented of mortality clinical trials focussed on the inhibition of the renin–angiotensin–aldosterone system on different levels in patients with chronic heart failure. The first study, CONSENSUS, was published in 1987 and showed that the ACE-inhibitor enalapril clearly reduced mortality in severe heart failure compared with placebo. This was followed by studies with beta blockers, angiotensin II type 1 receptor blockers, ...
Source: Cor et Vasa - July 5, 2018 Category: Cardiology Source Type: research

Arrhythmogenic cardiomyopathy of left ventricle. A rare event, but possible
Publication date: Available online 23 October 2017Source: Cor et VasaAuthor(s): Michele Scarano, Germana Gizzi, Cesare MantiniAbstractArrhythmogenic right ventricular dysplasia (ARVD) is a form of inherited cardiomyopathy characterized by fibro-fatty substitution mainly right ventricular (RV). Affected patients may succumb to life-threatening ventricular arrhythmias and heart failure. It is even more common among athletes who experience sudden cardiac death (SCD). The disease involvement is not limited only to the RV, but the left ventricle (LV) can also be involved. We have reported a case of a 38 years-old man, with two ...
Source: Cor et Vasa - July 5, 2018 Category: Cardiology Source Type: research

Toxins Are an Excellent Source of Therapeutic Agents against Cardiovascular Diseases
Semin Thromb Hemost DOI: 10.1055/s-0038-1661384Venomous and hematophagous animals use their venom or saliva for survival, to obtain food, and for self-defense. Venom and saliva from these animals are cocktails of bioactive molecules primarily composed of proteins and peptides. These molecules are called toxins because they cause unwanted consequences on prey. They exhibit unique, diverse, and specific biological activities that perturb normal physiological processes of their prey and host. However, the potential of toxins as inspirations for the development of therapeutic agents or pharmacological tools has also long been ...
Source: Seminars in Thrombosis and Hemostasis - June 28, 2018 Category: Hematology Authors: Koh, Cho Yeow Modahl, Cassandra M. Kulkarni, Namrata Kini, R. Manjunatha Tags: Review Article Source Type: research

Cost-Effectiveness Analysis of Sacubitril-Valsartan Compared with Enalapril in Patients with Heart Failure with Reduced Ejection Fraction in Thailand
ConclusionsAt its current price in Thailand, sacubitril-valsartan may not represent good value for the nations ’s limited healthcare resources. The cost of sacubitril-valsartan needs to reduce by approximately 2% to yield an ICER below the threshold. (Source: American Journal of Cardiovascular Drugs)
Source: American Journal of Cardiovascular Drugs - June 21, 2018 Category: Cardiology Source Type: research

Neprilysin Inhibitors: Filling a Gap in Heart Failure Management, Albeit Amidst Controversy and at a Significant Cost
AbstractDual angiotensin and neprilysin inhibition using the combination drug sacubitril –valsartan has ushered in a new era in the treatment of heart failure (HF). The randomized controlled PARADIGM-HF trial, which randomized 8399 patients with HF to enalapril or sacubitril–valsartan, showed a 20% reduction in mortality and HF hospitalization with the new drug. This has been herald ed as a step toward filling a crucial gap in HF management by providing strong evidence that combined inhibition of the angiotensin receptor and neprilysin is superior to inhibition of the renin–angiotensin system alone in sta...
Source: American Journal of Cardiovascular Drugs - June 20, 2018 Category: Cardiology Source Type: research

Aldosterone downregulates delayed rectifier potassium currents through an angiotensin type 1 receptor-dependent mechanism.
Authors: Lv Y, Wang Y, Zhu X, Zhang H Abstract We have previously shown that aldosterone downregulates delayed rectifier potassium currents (IKs) via activation of the mineralocorticoid receptor (MR) in adult guinea pig cardiomyocytes. Here, we investigate whether angiotensin II/angiotensin type 1 receptor (AngII/AT1R) and intracellular calcium also play a role in these effects. Ventricular cardiomyocytes were isolated from adult guinea pigs and incubated with aldosterone (1 μmol·L-1) either alone or in combination with enalapril (1 μmol·L-1), losartan (1 μmol·L-1), nimodipine (1 μm...
Source: American Journal of Translational Research - June 12, 2018 Category: Research Tags: Am J Transl Res Source Type: research

The renal blood flow reserve in healthy humans and patients with atherosclerotic renovascular disease measured by positron emission tomography using [ 15 O]H 2 O
ConclusionsThis study is the first to report [15O]H2O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [15O]H2O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [15O]H2O PET method in evaluation of renal blood flow. (Source: EJNMMI Research)
Source: EJNMMI Research - June 11, 2018 Category: Radiology Source Type: research

Diuretic herb Gomphrena celosioides Mart. (Amaranthaceae) promotes sustained arterial pressure reduction and protection from cardiac remodeling on rats with renovascular hypertension
Conclusions The G. celosioides diuretic effect is maintained on renovascular hypertensive rats and can reduce the blood pressure after the first week of treatment by inhibiting ACE and these effects are longstanding and strong enough to promote protection against cardiac remodeling. Therefore, it shows potential as an antihypertensive drug. Graphical abstract (Source: Journal of Ethnopharmacology)
Source: Journal of Ethnopharmacology - June 6, 2018 Category: Drugs & Pharmacology Source Type: research

Was the Enalapril Dose Too Low in the PARADIGM-HF Trial?
In conclusion, based on current evidence, it is unclear whether a maximum recommended enalapril dose would promote improved patient outcomes compared with an intermediate dose. However, no prospective study to date comparing ACE inhibitor doses has documented that higher doses result in significant mortality reduction, although the data suggest that there may be a decrease in HF hospitalizations when compared with lower doses. (Source: Cardiology in Review)
Source: Cardiology in Review - June 5, 2018 Category: Cardiology Tags: Review Articles Source Type: research

Angiotensin receptor-neprilysin inhibitors: A new paradigm in heart failure with reduced ejection fraction
Despite significant advances in the last 30  years in reducing morbidity and mortality from heart failure with reduced ejection fraction (HFrEF) with pharmacological and device-based therapies, patients remain at a high risk of adverse cardiovascular outcomes. Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitors (ARNI), has been shown to reduce the risk of cardiovascular death or heart failure hospitalisation and improve symptoms in patients with chronic, ambulatory, symptomatic HFrEF in a large, phase 3, multicentre, international, randomised controlled trial, PARADIGM-HF, when compared to t...
Source: International Journal of Cardiology - June 1, 2018 Category: Cardiology Authors: Kieran F. Docherty, John J.V. McMurray Source Type: research

Continuous inkjet printing of enalapril maleate onto orodispersible film formulations
In conclusion, it was feasible to print EM doses onto drug-free and HCT ODFs during an in-line continuous manufacturing process. Graphical abstract (Source: International Journal of Pharmaceutics)
Source: International Journal of Pharmaceutics - May 26, 2018 Category: Drugs & Pharmacology Source Type: research

Dissecting the heart/brain interaction in post-infarct myocardial inflammation by whole body translocator protein (TSPO) imaging
102Purpose: Acute myocardial infarction (MI) leads to local and systemic inflammation, which is a determinant of subsequent left ventricular remodeling. Prior work has shown that both acute infarct and chronic remodeling are associated with neuroinflammation. which can be attenuated by angiotensin blockade. We aimed to determine the impact of early anti-inflammatory and/or late anti-remodeling effects of angiotensin convertning enzyme inhibition using TSPO-targeted whole body PET. Methods: C57Bl/6 mice underwent permanent coronary artery ligation (n=30) or sham surgery (n=5). Subgroups of mice were treated with enalapril, ...
Source: Journal of Nuclear Medicine - May 23, 2018 Category: Nuclear Medicine Authors: Borchert, T., Hess, A., Ross, T., Bengel, F., Thackeray, J. Tags: Cardiovascular Molecular Imaging: Innervation and Inflammation Source Type: research

Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats
Conclusions A 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells. Graphical abstract (Source: Phytomedicine)
Source: Phytomedicine - May 19, 2018 Category: Drugs & Pharmacology Source Type: research

Angioedema in heart failure patients treated with sacubitril/valsartan (LCZ696) or enalapril in the PARADIGM-HF study
PARADIGM-HF demonstrated significant clinical benefits for sacubitril/valsartan (LCZ696, an angiotensin receptor neprilysin inhibitor) versus the angiotensin-converting enzyme inhibitor (ACEI) enalapril in patients with heart failure with reduced ejection fraction. As inhibition of ACE, and co-inhibition of ACE and neprilysin, may increase the risk of angioedema, this was an adverse event of special interest. (Source: International Journal of Cardiology)
Source: International Journal of Cardiology - May 16, 2018 Category: Cardiology Authors: Victor Shi, Michele Senni, Hendrik Streefkerk, Vikas Modgill, Wenchun Zhou, Allen Kaplan Source Type: research

Independent Prognostic Value of Serum Soluble ST2 Measurements in Patients With Heart Failure and a Reduced Ejection Fraction in the PARADIGM-HF Trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) [Original Articles]
Conclusions: Sacubitril/valsartan resulted in greater reductions and less increases in sST2 levels than enalapril. No specific threshold was associated with risk, as linear relationships between baseline sST2 and outcomes were observed. Changes in sST2 from baseline to 1 month were independently associated with the risk of outcomes. Clinical Trial Registration : URL: https://www.clinicaltrials.gov. Unique identifier: NCT01035255. (Source: Circulation: Heart Failure)
Source: Circulation: Heart Failure - May 10, 2018 Category: Cardiology Authors: OMeara, E., Prescott, M. F., Claggett, B., Rouleau, J. L., Chiang, L.-M., Solomon, S. D., Packer, M., McMurray, J. J. V., Zile, M. R. Tags: Biomarkers, Clinical Studies, Fibrosis, Heart Failure, Prognosis Original Articles Source Type: research

The intervention of enalapril maleate and folic acid tablet on the expressions of the GRP78 and CHOP and vascular remodeling in the vascular smooth muscle cells of H-hypertensive rats with homocysteine.
Authors: Lu F, Zhao LY, Zhang ZM, Zou Q, Yu XL, Wei CY Abstract OBJECTIVE: GRP78 and CHOP play essential roles in endoplasmic reticulum stress (ERS) of the vascular smooth muscle cells. We aim to investigate the effect of enalapril maleate and folic acid tablet on the expressions of GRP78 and CHOP and vascular remodeling in a homocysteine (HCY)-treated hypertensive rat model. MATERIALS AND METHODS: The hypertensive rat model was established with the technique of coarctation in the abdominal aorta, and the blood pressure of the rat was measured with the non-destructive tail-cuff method two weeks after operation....
Source: European Review for Medical and Pharmacological Sciences - April 26, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Sacubitril/Valsartan: From Clinical Trials to Real-world Experience
AbstractPurpose of reviewCompared to enalapril, use of angiotensin-receptor blocker and neprilysin inhibitor sacubitril/valsartan to treat patients with heart failure and reduced ejection fraction (HFrEF) is associated with substantial reductions in both cardiovascular mortality and heart failure progression. The purpose of this review is to discuss the real-world experience of sacubitril/valsartan.Recent findingsIn the years following the publication of the landmark PARADIGM-HF trial in 2014 and its subsequent FDA approval, a growing evidence base supports the safety and efficacy of sacubitril/valsartan in a broad spectru...
Source: Current Treatment Options in Cardiovascular Medicine - April 23, 2018 Category: Cardiology Source Type: research

Effect of neprilysin inhibition on renal function in patients with type 2 diabetes and chronic heart failure who are receiving target doses of inhibitors of the renin-angiotensin system: a secondary analysis of the PARADIGM-HF trial
Publication date: Available online 13 April 2018 Source:The Lancet Diabetes & Endocrinology Author(s): Milton Packer, Brian Claggett, Martin P Lefkowitz, John J V McMurray, Jean L Rouleau, Scott D Solomon, Michael R Zile Background Neprilysin inhibition has favourable effects on experimental diabetic nephropathy. We sought to assess the effects of neprilysin inhibition on the course of renal function in patients with type 2 diabetes. Methods In the randomised, double-blind PARADIGM-HF trial, the effects of sacubitril/valsartan (97 mg/103 mg twice daily) were compared with enalapril (10 mg twice daily) in 8399 pati...
Source: The Lancet Diabetes and Endocrinology - April 14, 2018 Category: Endocrinology Source Type: research

Renal Effects and Associated Outcomes During Angiotensin-Neprilysin Inhibition in Heart Failure
Conclusions Compared with enalapril, sacubitril/valsartan led to a slower rate of decrease in the eGFR and improved cardiovascular outcomes, even in patients with chronic kidney disease, despite causing a modest increase in UACR. Graphical abstract (Source: JACC: Heart Failure)
Source: JACC: Heart Failure - April 12, 2018 Category: Cardiology Source Type: research

Incidence, Predictors, and Outcomes Associated With Hypotensive Episodes Among Heart Failure Patients Receiving Sacubitril/Valsartan or Enalapril: The PARADIGM-HF Trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) [Original Articles]
Conclusions: Hypotension was more common with sacubitril/valsartan relative to enalapril in PARADIGM-HF but did not differentially affect permanent discontinuations. Patients with hypotension during run-in derived similar benefit from sacubitril/valsartan compared with enalapril as those who did not experience hypotension. (Source: Circulation: Heart Failure)
Source: Circulation: Heart Failure - April 11, 2018 Category: Cardiology Authors: Vardeny, O., Claggett, B., Kachadourian, J., Pearson, S. M., Desai, A. S., Packer, M., Rouleau, J., Zile, M. R., Swedberg, K., Lefkowitz, M., Shi, V., McMurray, J. J. V., Solomon, S. D. Tags: Clinical Studies, Heart Failure Original Articles Source Type: research

Abstract 125: Fewer Hospitalizations And Emergency Room Visits With Sacubitril/Valsartan Versus Angiotensin-Converting Enzyme Inhibitor Or Angiotensin-Receptor Blocker In A Retrospective Claims-Based Study Of Patients With Heart Failure [Session Title: Poster Session AM]
Introduction: Among patients with HFrEF, treatment with sacubitril/valsartan (SAC/VAL) was shown in PARADIGM-HF to reduce risks of CV death and HF hospitalization compared with enalapril; however, scarce data exist regarding the impact of SAC/VAL on real-world healthcare resource utilization (HCRU) compared to ACEI or ARB.Objective: To compare HCRU among patients with HFrEF treated with SAC/VAL vs. ACEI or ARB.Methods: Using managed care claims data, we identified stable adults with claims-based proxy for HFrEF and ≥1 claim for SAC/VAL (identified first), ACEI or ARB during Oct 2015 to Jun 2016. We required ≥80% prop...
Source: Circulation: Cardiovascular Quality and Outcomes - April 5, 2018 Category: Cardiology Authors: Albert, N. M., Swindle, J. P., Buysman, E. K., Chang, C. Tags: Session Title: Poster Session AM Source Type: research

Abstract 216: Hospitalizations of Patients With Heart Failure and Reduced Ejection Fraction Treated With Sacubitril/Valsartan (S/V) vs. Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker (ACEI/ARB) [Session Title: Poster Session PM]
Background: The PARADIGM-HF clinical trial showed a significant reduction in heart failure (HF) hospitalizations and cardiovascular (CV) death in patients with heart failure and reduced ejection fraction (HFrEF) and treated with S/V compared to enalapril. The impact of S/V on real-world outcomes is not well studied.Objective: To assess the association of hospitalization and therapy with S/V vs. ACEI/ARB in patients with HFrEF in the US.Methods: Adult patients with ≥1 claim for S/V or ACEI/ARB from 7/7/2015-5/31/2016 were selected from the MarketScan databases. Patients with S/V were assumed to have HFrEF based on its pr...
Source: Circulation: Cardiovascular Quality and Outcomes - April 5, 2018 Category: Cardiology Authors: Chang, C., Song, X., Nguyen, A., Smith, D., Choi, M., Duffy, C. Tags: Session Title: Poster Session PM Source Type: research

The Effect of a Nonpeptide Angiotensin II Type 2 Receptor Agonist, Compound 21, on Aortic Aneurysm Growth in a Mouse Model of Marfan Syndrome
This study confirms that angiotensin II type 1 receptor antagonism (losartan) decreases aortic aneurysm growth in a mouse model of MFS. A nonpeptide angiotensin II type 2 receptor agonist (C21), at the doses studied, was ineffective. Future studies are warranted to further elucidate the exact role of the RAA system in aneurysm formation in MFS and identify alternative targets for intervention. (Source: Journal of Cardiovascular Pharmacology)
Source: Journal of Cardiovascular Pharmacology - April 1, 2018 Category: Cardiology Tags: Original Article Source Type: research

Effects of Sacubitril/Valsartan on cardiovascular biomarkers in chronic heart failure patients
Conclusion The results showed that while sacubitril/valsartan decreased sNEP activity without no effect on the mNEP release. The increase in T71 proBNP glycosylation being responsible for the discrepancies between BNP and NT-proBNP plasma levels. (Source: Archives of Cardiovascular Diseases Supplements)
Source: Archives of Cardiovascular Diseases Supplements - March 23, 2018 Category: Cardiology Source Type: research

Anthracycline-induced cardiotoxicity: A multicenter randomised trial comparing two strategies for guiding prevention with enalapril: The International CardioOncology Society-one  trial
Low cumulative doses of anthracyclines in adult patients with low cardiovascular risk can raise troponins, without differences between the two strategies of giving enalapril. Considering a benefit of enalapril in the prevention of LV dysfunction, a troponin-triggered strategy may be more convenient. (Source: European Journal of Cancer)
Source: European Journal of Cancer - March 19, 2018 Category: Cancer & Oncology Authors: Daniela Cardinale, Fabio Ciceri, Roberto Latini, Maria Grazia Franzosi, Maria Teresa Sandri, Maurizio Civelli, GianFranco Cucchi, Elisabetta Menatti, Maurizio Mangiavacchi, Raffaele Cavina, Enrico Barbieri, Stefania Gori, Alessandro Colombo, Giuseppe Curi Tags: Original Research Source Type: research

Antidepressant-like effect of losartan involves TRKB transactivation from angiotensin receptor type 2 (AGTR2) and recruitment of FYN.
a SRL Abstract The renin-angiotensin system (RAS) is associated with peripheral fluid homeostasis and cardiovascular function, but recent evidence also suggests a functional role in the brain. RAS regulates physiological and behavioral parameters related to the stress response, including depressive symptoms. Apparently, RAS can modulate levels of brain-derived neurotrophic factor (BDNF) and TRKB, which are important in the neurobiology of depression and antidepressant action. However, the interaction between the BDNF/TRKB system and RAS in depression has not been investigated before. Accordingly, in the forced swi...
Source: Neuropharmacology - March 14, 2018 Category: Drugs & Pharmacology Authors: Diniz CRAF, Casarotto PC, Fred SM, Biojone C, Castrén E, Joca SRL Tags: Neuropharmacology Source Type: research

Transforming growth factor- β1 (TGF-β1) induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways.
Transforming growth factor-β1 (TGF-β1) induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways. Can J Physiol Pharmacol. 2018 Mar 05;: Authors: Ongali B, Nicolakakis N, Tong XK, Lecrux C, Imboden H, Hamel EE Abstract Transgenic mice constitutively overexpressing the cytokine transforming growth factor-β1 (TGF-β1) (TGF mice) display cerebrovascular alterations as seen in Alzheimer's disease (AD) and vascular cognitive impairment and dementia (VCID), but no or only subtle cognitive deficits. TGF-β1 may exert part of...
Source: Canadian Journal of Physiology and Pharmacology - March 5, 2018 Category: Drugs & Pharmacology Authors: Ongali B, Nicolakakis N, Tong XK, Lecrux C, Imboden H, Hamel EE Tags: Can J Physiol Pharmacol Source Type: research

Heart failure and inhibition of renin –angiotensin–aldosterone system
Publication date: Available online 1 March 2018 Source:Cor et Vasa Author(s): Jiří Vítovec, Jindřich Špinar, Lenka Špinarová A historical survey is presented of mortality clinical trials focussed on the inhibition of the renin–angiotensin–aldosterone system on different levels in patients with chronic heart failure. The first study, CONSENSUS, was published in 1987 and showed that the ACE-inhibitor enalapril clearly reduced mortality in severe heart failure compared with placebo. This was followed by studies with beta blockers, angiotensin II type 1 receptor blockers, block...
Source: Cor et Vasa - March 2, 2018 Category: Cardiology Source Type: research

[A novel agent in the treatment of heart failure with depressed systolic function].
CONCLUSIONS: Death due to cardiovascular causes, or hospital admission due to heart failure (the primary endpoint) occurred in 914 patients (21.8%) in the Sacubitril / valsartán group, and 1117 patients (26.5%) in the enalapril group (risk ratio in the sacubitril / valsartán group, 0.80, with a 95% confidence interval [CI]: 0.73 to 0.87, P
Source: Archivos de Cardiologia de Mexico - February 28, 2018 Category: Cardiology Authors: Duarte Vera YC, Cáceres Vinueza SV, Daher Nader JE, Lara Terán JF Tags: Arch Cardiol Mex Source Type: research