Congestive heart failure angiotensin receptor-neprilysin inhibitor
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Resident Survival Guide |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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 hospitalization . 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]
References
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.