Congestive heart failure angiotensin receptor-neprilysin inhibitor

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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
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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]; 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.

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 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.

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

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