Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure

• Published in: The New England journal of medicine Vol. 371; no. 11; pp. 993 - 1004
• Main Authors: McMurray, John J.V, Packer, Milton, Desai, Akshay S, Gong, Jianjian, Lefkowitz, Martin P, Rizkala, Adel R, Rouleau, Jean L, Shi, Victor C, Solomon, Scott D, Swedberg, Karl, Zile, Michael R
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 11-09-2014
• Subjects: Aged; Aminobutyrates - adverse effects; Aminobutyrates - therapeutic use; Angioedema; Angiotensin; Angiotensin Receptor Antagonists - adverse effects; Angiotensin Receptor Antagonists - therapeutic use; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Clinical Medicine; CONVERTING ENZYME-INHIBITION; Cough; Death; DOUBLE-BLIND; Double-Blind Method; Drug Combinations; Drug therapy; EJECTION FRACTION; Enalapril - adverse effects; Enalapril - therapeutic use; Enzymes; Female; General & Internal; General aspects; Heart; Heart diseases; Heart failure; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hospitalization - statistics & numerical data; Humans; Hyperkalemia; Hypotension; Kaplan-Meier Estimate; Klinisk medicin; Male; Medical sciences; Medicine; Middle Aged; MORBIDITY; MORTALITY; NATRIURETIC-PEPTIDE; Neprilysin; Neprilysin - antagonists & inhibitors; NEUTRAL ENDOPEPTIDASE INHIBITION; RANDOMIZED-TRIAL; RECEPTOR; Statistical analysis; Stroke Volume; SURVIVAL; Tetrazoles - adverse effects; Tetrazoles - therapeutic use; Heart failure; Enzyme; Enzyme inhibitor; Cardiovascular disease; Medicine; Peptidases; Enalapril; Peptidyl-dipeptidase A; Heart disease; Angiotensin; Hydrolases; Peptidyl-dipeptidases; Antihypertensive agent; ACE inhibitor; Comparative study
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1409077

The angiotensin receptor–neprilysin inhibitor LCZ696 was compared with the ACE inhibitor enalapril in patients with advanced heart failure. LCZ696 was superior to enalapril in all outcomes. Neprilysin inhibition may replace ACE inhibition for the treatment of heart failure.
Angiotensin-converting–enzyme (ACE) inhibitors have been the cornerstone of the treatment for heart failure and a reduced ejection fraction for nearly 25 years, since enalapril was shown to reduce the risk of death in two trials.
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Long-term treatment with enalapril decreased the relative risk of death by 16% among patients with mild-to-moderate symptoms.
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The effect of angiotensin-receptor blockers (ARBs) on mortality has been inconsistent,
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and thus, these drugs are recommended primarily for patients who have unacceptable side effects (primarily cough) while receiving ACE inhibitors. Subsequent studies showed that the use of beta-blockers and mineralocorticoid-receptor antagonists, when added to ACE . . .