Sacubitril/valsartan

Sacubitril/valsartan is a fixed-dose medicine combining the neprilysin inhibitor sacubitril with the angiotensin receptor blocker valsartan. It reduces cardiovascular death and heart-failure hospitalization in eligible patients with chronic heart failure.

Neprilysin: Neprilysin is an enzyme that breaks down natriuretic peptides and other signaling molecules. Sacubitril blocks this enzyme, increasing the availability of natriuretic peptides.
Heart failure with reduced ejection fraction: Heart failure with reduced ejection fraction is a syndrome in which the left ventricle pumps out an abnormally low fraction of its blood. This is the heart-failure group with the clearest established benefit from the medicine.
Enalapril: Enalapril is an angiotensin-converting enzyme inhibitor used to treat hypertension and heart failure. PARADIGM-HF compared the combination against enalapril as active treatment.
Left ventricular ejection fraction: Left ventricular ejection fraction is the percentage of blood in the left ventricle expelled with each contraction. It helps classify heart failure and guide decisions about the combination.
PARADIGM-HF trial: PARADIGM-HF was a randomized, double-blind trial of sacubitril/valsartan versus enalapril in heart failure with reduced ejection fraction. Its results drove a major change in treatment recommendations for eligible patients.
Natriuretic peptides: Natriuretic peptides are hormones that promote sodium excretion, blood-vessel relaxation, and reduced cardiac strain. Their effects are enhanced when sacubitril slows their breakdown.
Heart failure with preserved ejection fraction: Heart failure with preserved ejection fraction causes heart-failure symptoms despite a left ventricular ejection fraction that is not substantially reduced. Evidence supports possible benefit for selected patients, especially toward the lower end of preserved ejection fraction.
ACE inhibitor: An ACE inhibitor blocks angiotensin-converting enzyme, reducing formation of angiotensin II and breakdown of bradykinin. Sacubitril/valsartan is generally used instead of, not together with, an ACE inhibitor.
Hypotension: Hypotension is blood pressure low enough to cause symptoms or impair organ perfusion. Blood-pressure reduction can limit treatment initiation or dose escalation.
Heart-failure guidelines: Heart-failure guidelines are evidence-based recommendations for diagnosis and treatment issued by professional organizations. Guidelines incorporated the combination into recommended therapy for selected patients.

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