Why sacubitril and velsartans uses in combination
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FDA Entresto prescribing information sacubitril valsartan mechanism combination
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Sacubitril and valsartan are combined because they act through two complementary pathways in heart failure with reduced ejection fraction (HFrEF).
- Sacubitril inhibits neprilysin, an enzyme that breaks down beneficial natriuretic peptides. This increases natriuresis and diuresis, vasodilation, and reduces cardiac remodeling.
- But neprilysin also breaks down angiotensin II. If used alone, sacubitril could raise angiotensin II, causing vasoconstriction, salt/water retention, and harmful remodeling.
- Valsartan is an ARB that blocks the angiotensin II AT1 receptor, preventing those harmful effects.
So the combination gives the benefit of increased natriuretic peptides while blocking the renin-angiotensin system. It is called an ARNI: angiotensin receptor-neprilysin inhibitor.
It is used mainly in symptomatic HFrEF to lower the risk of cardiovascular death and heart-failure hospitalization compared with ACE-inhibitor therapy in appropriate patients.
Important: do not combine it with an ACE inhibitor. A 36-hour washout is required when switching from an ACE inhibitor because of increased angioedema risk.Sacubitril and valsartan are used together because they act on two harmful or helpful pathways in heart failure at the same time. The combination is called an ARNI: angiotensin receptor-neprilysin inhibitor.
- Sacubitril inhibits neprilysin. This raises natural natriuretic peptides, which promote salt and water excretion, widen blood vessels, and reduce cardiac strain.
- But neprilysin inhibition alone can also increase angiotensin II activity, which causes vasoconstriction, sodium retention, and cardiac remodeling.
- Valsartan blocks the angiotensin-II AT1 receptor, preventing those angiotensin-II effects.
So valsartan counterbalances the unwanted renin-angiotensin system activation associated with neprilysin inhibition, while sacubitril adds beneficial natriuretic-peptide effects. Together they lower preload/afterload and oppose adverse remodeling more effectively than either strategy alone. The FDA prescribing information describes this dual mechanism.
This combination is mainly used for heart failure, especially symptomatic heart failure with reduced ejection fraction, to reduce cardiovascular death and hospitalizations.
Important: Do not take it together with an ACE inhibitor, such as enalapril or lisinopril. A 36-hour washout is required when changing from an ACE inhibitor because the combination increases the risk of angioedema. It can also cause low blood pressure, high potassium, and worsening kidney function, so monitoring is needed.
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