Congestive heart failure angiotensin receptor-neprilysin inhibitor

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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
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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
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [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.

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. The PARADIGM-HF study evaluated LCZ696, a concomitant inhibitor of neprilysin and angiotensin inhibitors. 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 educed 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.

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