Table 1: Important Neurohormonal Systems and their Blockade in Heart Failure.

Neurohormonal system	Maladaptive effects	Drug class	Efficacy of blockade	Notes
Sympathetic nervous system	Cardiovascular hypertrophy and fibrosis, apoptosis, arrhythmia	Beta-blocker Alpha-blocker Sympatholytic	Reduced morbidity and mortality (only patients in sinus rhythm) No morbidity or mortality benefit No benefit; possible harm	Class I indication No indication No indication
Renin–angiotensin–aldosterone system	Cardiovascular and renal fibrosis, hypertrophy, salt and water retention	ACE inhibitor Angiotensin receptor blocker Mineralocorticoid receptor antagonist	Reduced morbidity and mortality Reduced morbidity and mortality Reduced morbidity and mortality	Class I indication Class I indication if intolerant to ACE inhibitor Class I indication
Endothelin system	Vasoconstriction, cardiovascular fibrosis, hypertrophy	Endothelin receptor antagonist Endothelin-converting enzyme inhibitor	No morbidity or mortality benefit No data available	Useful in some forms of pulmonary hypertension Not evaluated in randomised trials
Natriuretic peptides	Counteracts the renin–angiotensin–aldosterone system in heart failure: natriuresis, diuresis, antifibrotic, antihypertrophic, blood	Neprilysin inhibitor (single- acting) pressure-lowering Vasopeptidase inhibitor (dual-acting) Angiotensin receptor neprilysin inhibitor (dual-acting)	No morbidity or mortality benefit Uncertain morbidity and mortality benefit Greater reduction in morbidity and mortality than ACE inhibitor	Not evaluated in large randomised-controlled trials Abandoned due to safety concerns Class I indication if symptomatic despite ACE inhibitor, beta- blocker and mineralocorticoid receptor antagonist

ACE = angiotensin-converting enzyme.