Read by QxMD icon Read


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
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
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...
October 10, 2016: International Journal of Clinical Pharmacology and Therapeutics
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
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
Loretta Fala
No abstract text is available yet for this article.
March 2016: American Health & Drug Benefits
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
(no author information available yet)
BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD...
September 19, 2016: Nephrology, Dialysis, Transplantation
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
Dennis J Cada, Danial E Baker, James Leonard
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line...
November 2015: Hospital Pharmacy
Naoki Okumura, 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: In the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure), the angiotensin receptor neprilysin inhibitor sacubitril/valsartan was more effective than the angiotensin-converting enzyme inhibitorenalapril in patients with heart failure and reduced ejection fraction. We examined whether this benefit was consistent irrespective of background therapy. METHODS AND RESULTS: We examined the effect of study treatment in the following subgroups: diuretics (yes/no), digitalis glycoside (yes/no), mineralocorticoid receptor antagonist (yes/no),and defibrillating device (implanted defibrillating device, yes/no)...
September 2016: Circulation. Heart Failure
Bruno M L Rocha, Luiz Menezes Falcão
Heart failure (HF) is an increasingly prevalent syndrome and a leading cause of both first hospitalization and readmissions. Strikingly, up to 25% of the patients are readmitted within 30 to 60-days, accounting for HF as the primary cause for readmission in the adult population. Given its poor prognosis, one could describe it as a "malignant condition". Acute decompensation is intrinsically related to increased right heart tele-diastolic pressures and often related to congestive symptoms. In-hospital strategies to adequately compensate and timely discharge patients are limited...
November 15, 2016: International Journal of Cardiology
Srikanth Yandrapalli, Wilbert S Aronow, Pratik Mondal, David R Chabbott
BACKGROUND: The PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure) trial was a double-blind trial that randomized 8442 patients with heart failure (HF) with reduced ejection fraction (HFrEF) to receive twice daily dosing of either 200 mg of LCZ696 or 10 mg of enalapril in addition to standard medical therapy for HF. AREAS OF UNCERTAINTY: Limitations of this trial include (1) sacubitril has not been tested by itself in the treatment of HFrEF; (2) the maximum recommended dose of valsartan for the treatment of HFrEF was used in this trial, but the maximum recommended dose of enalapril for the treatment of HFrEF was not used; (3) a run-in phase was used in this trial to test the tolerability of LCZ696, and patients who had adverse effects in this period were excluded from randomization; (4) the percent of blacks enrolled in this trial was only 5%; (5) LCZ696 caused a 14% incidence of hypotension; (6) neprilysin inhibition might favor the development of Alzheimer dementia, which was not assessed in the PARADIGM-HF trial; (7) patients with severe symptomatic HF were underrepresented in this trial; (8) major exclusions from this trial included an acute coronary event in the last 3 months, severe pulmonary disease, hepatic impairment, and an estimated glomerular filtration rate <30 mL per minute per 1...
August 17, 2016: American Journal of Therapeutics
Dimitrios Farmakis, Vassiliki Bistola, Apostolos Karavidas, John Parissis
The combination of neprilysin inhibitor sacubitril with the angiotensin II receptor 1 blocker valsartan is the first agent from the angiotensin receptor neprilysin inhibitors (ARNI) class authorized for clinical use in heart failure (HF) patients with reduced ejection fraction (HFrEF). Sacubitril/valsartan resulted in 20% reduction in the incidence rate of death or HF hospitalization compared to enalapril in symptomatic HFrEF patients in the seminal PARADIGM-HF trial. As a result, the recently updated European and American HF guidelines granted this agent a class IB indication for the treatment of ambulatory/chronic symptomatic HFrEF patients...
November 15, 2016: International Journal of Cardiology
Milton Packer, W Mark Armstrong, Joseph M Rothstein, Michael Emmett
No abstract text is available yet for this article.
August 30, 2016: Annals of Internal Medicine
Alexander T Sandhu, Daniel A Ollendorf, Richard H Chapman, Steven D Pearson, Paul A Heidenreich
Background: Sacubitril-valsartan therapy reduces cardiovascular mortality compared with enalapril therapy in patients with heart failure with reduced ejection fraction. Objective: To evaluate the cost-effectiveness of sacubitril-valsartan versus angiotensin-converting enzyme inhibitor therapy in patients with chronic heart failure. Design: Markov decision model. Data Sources: Clinical trials, observational analyses, reimbursement data from the Centers for Medicare & Medicaid Services, drug pricing databases, and Centers for Disease Control and Prevention life tables...
August 30, 2016: Annals of Internal Medicine
Jens Jordan, Rudi Stinkens, Thomas Jax, Stefan Engeli, Ellen E Blaak, Marcus May, Bas Havekes, Christoph Schindler, Diego Albrecht, Parasar Pal, Tim Heise, Gijs H Goossens, Thomas H Langenickel
Natriuretic peptide (NP) deficiency and sustained renin-angiotensin system activation are associated with impaired oxidative metabolism and predispose to type-2 diabetes. We hypothesized that sacubitril/valsartan (LCZ696), which augments NP through neprilysin inhibition while blocking angiotensin II type-1 (AT1)-receptors improves insulin sensitivity, lipid mobilization, and oxidation. Following 8 weeks of treatment of obese hypertensive patients, sacubitril/valsartan 400 mg QD, but not amlodipine 10 mg QD, was associated with a significant increase from baseline in insulin sensitivity index (hyperinsulinemic-euglycemic clamp), and tended to be higher in patients treated with sacubitril/valsartan compared with amlodipine...
August 20, 2016: Clinical Pharmacology and Therapeutics
Milton Packer
Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition...
October 2016: European Journal of Heart Failure
Achim Lother, Lutz Hein
Chronic heart failure is one of the leading causes for hospitalization in the United States and Europe, and is accompanied by high mortality. Current pharmacological therapy of chronic heart failure with reduced ejection fraction is largely based on compounds that inhibit the detrimental action of the adrenergic and the renin-angiotensin-aldosterone systems on the heart. More than one decade after spironolactone, two novel therapeutic principles have been added to the very recently released guidelines on heart failure therapy: the HCN-channel inhibitor ivabradine and the combined angiotensin and neprilysin inhibitor valsartan/sacubitril...
October 2016: Pharmacology & Therapeutics
Thomas A Gaziano, Gregg C Fonarow, Brian Claggett, Wing W Chan, Celine Deschaseaux-Voinet, Stuart J Turner, Jean L Rouleau, Michael R Zile, John J V McMurray, Scott D Solomon
IMPORTANCE: The angiotensin receptor neprilysin inhibitor sacubitril/valsartan was associated with a reduction in cardiovascular mortality, all-cause mortality, and hospitalizations compared with enalapril. Sacubitril/valsartan has been approved for use in heart failure (HF) with reduced ejection fraction in the United States and cost has been suggested as 1 factor that will influence the use of this agent. OBJECTIVE: To estimate the cost-effectiveness of sacubitril/valsartan vs enalapril in the United States...
September 1, 2016: JAMA Cardiology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"