Congestive heart failure angiotensin receptor-neprilysin inhibitor

Jump to: navigation, search
Siren.gif

Resident
Survival
Guide
Congestive Heart Failure Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Systolic Dysfunction
Diastolic Dysfunction
HFpEF
HFrEF

Causes

Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

Cardiac MRI

Echocardiography

Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies

Treatment

Invasive Hemodynamic Monitoring

Medical Therapy:

Summary
Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
Diuretics
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Nitrates
Hydralazine
Positive Inotropics
Anticoagulants
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Ultrafiltration
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure angiotensin receptor-neprilysin inhibitor On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Congestive heart failure angiotensin receptor-neprilysin inhibitor

CDC on Congestive heart failure angiotensin receptor-neprilysin inhibitor

Congestive heart failure angiotensin receptor-neprilysin inhibitor in the news

Blogs on Congestive heart failure angiotensin receptor-neprilysin inhibitor

Directions to Hospitals Treating Congestive heart failure angiotensin receptor-neprilysin inhibitor

Risk calculators and risk factors for Congestive heart failure angiotensin receptor-neprilysin inhibitor

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2],Seyedmahdi Pahlavani, M.D. [3]

Overview

The PARADIGM-HF study evaluated the efficacy of LCZ696, a concomitant inhibitor of neprilysin and angiotensin receptor, on the rate of mortality due to cardiovascular causes and hospitalization. Compared to enalapril, angiotensin receptor-neprilysin inhibitor significantly reduced the rate of hospitalization by 21% and decreased the rate of cardiovascular and hospitalization-related deaths from 26.5% to 21.8%. The administration of angiotensin receptor-neprilysin inhibitor reduced chronic heart failure symptoms and the associated limitation of physical activity.[1]

Angiotensin Receptor-Neprilysin Inhibitor

The inhibition of neprilysin, a neutral endopeptidase, has been associated with a decrease in vasoactive peptides among patients with heart failure. In fact, neprilysin inhibition decreases the breakdown of natriuretic peptide, bradykinin, and adrenomedullin leading to an attenuation of sodium retention and vasoconstriction observed in heart failure patients.[2][3][4]

Animal studies revealed that the effect of neprilysin inhibition is further potentiated with the concomitant inhibition of the renin angiotensin system by the administration of ACE inhibitors at the expense of an increased risk of angioedema.[5] The PARADIGM-HF study evaluated the efficacy of LCZ696, a concomitant inhibitor of neprilysin and angiotensin receptor, on the rate of mortality due to cardiovascular causes and hospitalizations. PARADIGM-HF randomized 8442 chronic heart failure patients with an ejection fraction inferior to 40% to either enalapril or angiotensin receptor-neprilysin inhibitor. Compared to enalapril, angiotensin receptor-neprilysin inhibitor significantly reduced the rate of hospitalization by 21% and decreased the rate of cardiovascular and hospitalization-related deaths from 26.5% to 21.8%. The administration of angiotensin receptor-neprilysin inhibitor reduced chronic heart failure symptoms and the associated limitation of physical activity.[1]

Class I

1. In patients with chronic symptomatic HFrEF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality. (Class I, Level of Evidence: B-R)

Class III (Harm)

1. ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor. (Class III, Level of Evidence: B-R)

2. ARNI should not be administered to patients with a history of angioedema. (Class III, Level of Evidence: C-EO)

References

  1. 1.0 1.1 J. McMurray, M. Packer, M.D., A.S. Desai, M.D. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure. New England Journal of Medicine. Epub ahead of print. Accessed on August 30, 2014.
  2. Cruden NL, Fox KA, Ludlam CA, Johnston NR, Newby DE (2004). "Neutral endopeptidase inhibition augments vascular actions of bradykinin in patients treated with angiotensin-converting enzyme inhibition". Hypertension. 44 (6): 913–8. doi:10.1161/01.HYP.0000146483.78994.56. PMID 15492133.
  3. Rademaker MT, Charles CJ, Espiner EA, Nicholls MG, Richards AM, Kosoglou T (1996). "Neutral endopeptidase inhibition: augmented atrial and brain natriuretic peptide, haemodynamic and natriuretic responses in ovine heart failure". Clin Sci (Lond). 91 (3): 283–91. PMID 8869410.
  4. Wilkinson IB, McEniery CM, Bongaerts KH, MacCallum H, Webb DJ, Cockcroft JR (2001). "Adrenomedullin (ADM) in the human forearm vascular bed: effect of neutral endopeptidase inhibition and comparison with proadrenomedullin NH2-terminal 20 peptide (PAMP)". Br J Clin Pharmacol. 52 (2): 159–64. PMC 2014526. PMID 11488772.
  5. Rademaker MT, Charles CJ, Espiner EA, Nicholls MG, Richards AM, Kosoglou T (1998). "Combined neutral endopeptidase and angiotensin-converting enzyme inhibition in heart failure: role of natriuretic peptides and angiotensin II". J Cardiovasc Pharmacol. 31 (1): 116–25. PMID 9456286.



Linked-in.jpg