10.11: Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral endopeptidase inhibitors to counter the harmful effects of neurohumoral activation on the heart, blood vessels, and kidneys.
ACEIs work by reducing angiotensin II levels. They have several physiological effects, including vasodilation, reduced aldosterone release, anti-remodeling effects on the heart, and sympatholytic effects. ACEIs can cause dry cough or rare angioedema due to increased bradykinin and substance P levels. ARBs are highly selective AT1 receptor antagonists used as alternatives to ACEIs in patients who cannot tolerate them. They can increase hypotension, hyperkalemia, and renal dysfunction. β-blockers reduce the actions of catecholamines on β-adrenoceptors, leading to decreased heart rate, force, and AV conduction. They also suppress arrhythmias and lower renin levels and may have varying effects on bronchoconstriction and vasoconstriction. MRAs, such as spironolactone and eplerenone, block aldosterone receptors and reduce fibrosis. These drugs have a documented life-prolonging effect in heart failure patients but can precipitate dysmenorrhea, gynecomastia, and hyperkalemia. Sacubitril/valsartan, a combination drug, activates the beneficial axis of neurohumoral activation and provides multiple benefits such as natriuresis, vasodilation, inhibition of thrombosis, and cardiac remodeling. ACEIs and ARBs reduce peripheral resistance, afterload, salt/water retention, and sympathetic activity. ACEIs are the preferred initial treatment for left ventricular dysfunction without edema. ARBs are alternatives for patients intolerant to ACEIs.
