21/09/2026
Mode of action of medications used in heart failure...
ARBS/ACEI/ARNI...
Each of the renin-angiotensin system antagonists (angiotensin-converting enzyme [ACE] inhibitor, single agent angiotensin II receptor blocker [ARB], and angiotensin receptor-neprilysin inhibitor [ARNI]) blocks harmful effects of renin-angiotensin-aldosterone system activation and attenuates adverse cardiac and vascular remodeling. Neprilysin inhibition contributes to the clinical effects of ARNI by inhibiting the levels of natriuretic peptides and/or other peptides that are degraded by neprilysin. ACE inhibitor and ARNI (but not single agent ARB) also raise levels of kinins which may have beneficial hemodynamic effects but also increase the risk of angioedema.
Betablockers
The mechanism of benefit from beta blocker therapy in patients with heart failure with reduced ejection fraction (HFrEF) is likely related to reducing detrimental effects of catecholamine stimulation including elevated heart rate, increased myocardial energy demands, adverse remodeling due to cardiac myocyte hypertrophy and death, interstitial fibrosis, impaired beta-adrenergic signaling, arrhythmia promotion, and stimulation of other detrimental systems such as the renin-angiotensin-aldosterone axis.
MRA
Mineralocorticoid receptor antagonist (MRA) therapy has diuretic and blood pressure lowering effects, raises serum potassium concentration via reduced urinary potassium loss, and blocks deleterious effects of aldosterone on the heart (including hypertrophy and fibrosis) and possibly other target organs such as kidney and blood vessels.
Sglt2 inhibitors
A number of mechanisms have been proposed for the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in preventing HF hospitalizations in patients with type 2 diabetes mellitus (DM) and improving outcomes in patients with HFrEF with or without DM. SGLT2 inhibitors promote osmotic diuresis and natriuresis, may promote vasodilation, improve myocardial metabolism, inhibit sodium-hydrogen exchange in myocardium, reduce cardiac fibrosis, and alter adipokine and cytokine production, as well as attenuate progression of renal dysfunction.
Hydralazine
The combined use of hydralazine and nitrates reduces cardiac afterload and preload, and may also enhance nitric oxide bioavailability.
Ivabridine
The mechanism of benefit from ivabradine in patients with HFrEF is likely slowing of the sinus rate.
Digoxin
acts by inhibiting the Na-K-ATPase pump, thus reducing the transport of sodium from the intracellular space in myocytes as well as noncardiac cells to the extracellular space. This mechanism contributes to digoxin’s hemodynamic, neurohumoral, and electrophysiologic effects
