New concept in the treatment of cardiovascular diseases - dual inhibition of neutral endopeptidase and RAA system
Abstract
Chronic heart failure leads to long-term activation of neurohumoral systems which have vasoconstricting effect, and cause sodium and water retention. Renin-angiotensin-aldosteron system (RAAS), and sympatoadrenal system (SAS) represent the main elements of these systems.
Their pharmacological blockage by angiotensin-converting enzyme (ACE) inhibitors or possible sartans has become together with beta-blockers the mainstay of chronic heart failure with reduced ejection fraction (HFrEF) treatment. In patients who are still symptomatic in spite of appropriate treatment, it is also recommended to add a mineralocorticoid receptor antagonist.
There are contraregulatory neurohumoral systems activated in chronic heart failure as well, causing vasodilation, natriuresis, and diuresis. The main constituent part of those contraregulatory systems being natriuretic peptides (NP).
Simultaneous inhibition of RAAS at the level of AT1 receptors for angiotensin II and inhibition of neprilysin - enzyme cleaving NPs into inactive metabolites - has been proven to be more effective compared to contemporary standard inhibition of RAAS at the level of ACE by PARADIGM-HF trial. Therefore the first dual inhibitor of both the angiotensin II receptors and the neprilysin (ARNI) sacubitril/valsartan has been added into the new guidelines for the treatment of chronic HFrEF.
It is recommended as more effective substitute for ACE inhibitor/sartan for outpatients who are still symptomatic in spite of existing treatment and are in stable clinical condition.