STEPTRACKERPHARMACOLOGY + PATHOPHYSIOLOGY | CARDIOVASCULAR | HIGH-YIELD REVIEW

Heart Failure Drugs

Separate the drugs that only relieve symptoms from the ones that make patients live longer — the second group all block neurohormonal overdrive.

FOCUS ON
↓ Mortality in HFrEF: ACEi / ARB / ARNI (sacubitril-valsartan), β-blockers (metoprolol succinate, carvedilol, bisoprolol), MRAs (spironolactone, eplerenone), SGLT2 inhibitors (dapagliflozin, empagliflozin), hydralazine + isosorbide dinitrate (Black patients). Symptom relief only: loop diuretics (congestion), digoxin (↓ hospitalizations). Ivabradine (If channel, SA node) lowers HR when β-blocker maxed. Acute decompensated: IV loop diuretic, vasodilator (nitroglycerin, nitroprusside), inotropes (dobutamine, milrinone) for low output. Digoxin: inhibits Na⁺/K⁺-ATPase → ↑ intracellular Ca²⁺ → ↑ contractility; vagal → ↓ AV conduction. Toxicity: nausea, vomiting, yellow-green vision, arrhythmias (atrial tachycardia with block, bidirectional VT), hyperkalemia (marker of toxicity); ↑ risk with hypokalemia, renal failure, verapamil, amiodarone, quinidine → digoxin Fab.
DRUG
MECHANISM
BENEFIT
WATCH FOR
ACEi · ARB
↓ Angiotensin II and aldosterone → ↓ afterload, preload, remodeling
↓ Mortality
↑ K⁺, cough, AKI
Sacubitril-valsartan (ARNI)
Neprilysin inhibitor (↑ natriuretic peptides) + ARB
↓ Mortality more than ACEi
Angioedema; 36-hour washout from ACEi · BNP rises (NT-proBNP still useful)
β-blockers
Block chronic sympathetic toxicity; ↓ HR
↓ Mortality, ↑ EF over months
Start low when euvolemic
Spironolactone · eplerenone
Aldosterone receptor block → ↓ fibrosis, K⁺ sparing
↓ Mortality (NYHA II–IV)
Hyperkalemia; gynecomastia (spironolactone)
SGLT2 inhibitors
Natriuresis, glycosuria, ↓ preload; cardiac metabolic effects
↓ Mortality, HF hospitalizations (with or without diabetes)
Genital mycotic infections, euglycemic DKA, volume depletion
Hydralazine + nitrate
Arteriolar + venous dilation
↓ Mortality in Black patients; ACEi-intolerant
Headache, lupus-like syndrome
Loop diuretics
Block NKCC2 → natriuresis
Relieve congestion, dyspnea
No mortality benefit · ↓ K⁺, ↓ Mg²⁺
Digoxin
Inhibits Na⁺/K⁺-ATPase → less Na⁺/Ca²⁺ exchange → ↑ Ca²⁺; ↑ vagal tone
↓ Symptoms and hospitalization; AF rate control
Narrow index · renally cleared
Ivabradine
Blocks funny current (If) in SA node
↓ HR (sinus rhythm, HR ≥ 70 on max β-blocker)
Luminous visual phenomena (phosphenes), bradycardia
Dobutamine
β1 agonist
Acute low-output HF
Arrhythmia
Milrinone
PDE3 inhibitor → ↑ cAMP in heart and vessels (inodilator)
Acute low output, bridge to transplant
Hypotension, arrhythmia; ↑ mortality long term
Nesiritide
Recombinant BNP → ↑ cGMP, vasodilation
Acute decompensated HF (rare)
Hypotension

Mechanism — how digoxin raises contractility

Blocks Na⁺/K⁺-ATPase
→
↑ Intracellular Na⁺
→
Na⁺/Ca²⁺ exchanger slows
→
↑ Ca²⁺ in SR → stronger beat

Hypokalemia lets more digoxin bind the pump (K⁺ competes for the same site) → toxicity.

Mortality vs symptoms

DRUG
↓ DEATH
↓ SYMPTOMS
ACEi/ARB/ARNI
Yes
Yes
β-blocker, MRA, SGLT2i
Yes
Yes
Loop diuretic
No
Yes
Digoxin
No
Yes

How it's tested

COMMON CONFUSIONHyperkalemia in digoxin overdose reflects pump poisoning (and predicts death); hypokalemia from diuretics is what predisposes to toxicity.
THE TRAPStarting an ARNI within 36 hours of an ACE inhibitor → angioedema risk (both raise bradykinin).
YOUR APPROACHHFrEF → stack the four mortality pillars (ARNI/ACEi, β-blocker, MRA, SGLT2i) → diuretic for congestion → special additions.

If you see… think…

Yellow-green halos, nausea on a cardiac drug → digoxin toxicity
Digoxin toxicity antidote → digoxin immune Fab
Starting amiodarone or verapamil with digoxin → ↑ digoxin levels
HF drug with phosphenes → ivabradine
HF drug that also lowers glucose → SGLT2 inhibitor
Neprilysin inhibition → sacubitril
Inodilator through PDE3 → milrinone
HFrEF in a Black patient on standard therapy → add hydralazine + isosorbide dinitrate
Gynecomastia on an HF drug → spironolactone → switch to eplerenone
Diuretics improve only → symptoms, not survival