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==Angiotensin Receptor-Neprilysin Inhibitor==
==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.


==References==
==References==

Revision as of 22:27, 30 August 2014



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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

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.

References


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