Sacubitril–valsartan and vasodilators in chronic heart failure
THE CONTEXT
Neprilysin inhibition augments endogenous peptide activity, while venous and arterial dilators reduce different components of cardiac loading.
Sacubitril and neprilysin inhibition
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Sacubitril inhibits neutral endopeptidase, also called neprilysin.
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Neprilysin breaks down the endogenous diuretics ANP and BNP, as well as vasoactive peptides including bradykinin and substance P.
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Combined with the angiotensin receptor blocker valsartan, sacubitril provides additional symptomatic and mortality benefit over ACE inhibition in chronic heart failure.
Vasodilators
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Vasodilators are valuable in chronic heart failure when ACE inhibitors or angiotensin receptor blockers are contraindicated.
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Venodilators such as nitrates reduce preload; arterial dilators such as hydralazine reduce afterload.
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Their use is limited by pharmacological tolerance and hypotension.