Heart failure (HF) activates two harmful compensatory systems: the sympathetic nervous system (tachycardia, vasoconstriction) and the renin–angiotensin–aldosterone system (RAAS) (sodium and water retention, vasoconstriction, ventricular remodeling). Most drugs that prolong life in HF work by blocking these systems; other drugs relieve symptoms by removing fluid or supporting contraction.

HF with reduced ejection fraction (HFrEF, LVEF ≤ 40%) — the four pillars of guideline-directed medical therapy (GDMT)

Symptom relief and selected clients

• Loop diuretics — furosemide (prototype), bumetanide, torsemide: relieve congestion in all HF types but do not reduce mortality
• Hydralazine + isosorbide dinitrate — added for self-identified Black clients with NYHA III–IV HFrEF on GDMT, or when RAAS inhibitors cannot be used
• Digoxin — reduces symptoms and hospitalization in selected clients; also used for rate control in atrial fibrillation (AF)
• Ivabradine — HFrEF with LVEF ≤ 35%, sinus rhythm, and resting heart rate ≥ 70/min despite the highest tolerated beta blocker dose
• Vericiguat (soluble guanylate cyclase stimulator) — selected HFrEF after a recent worsening event
• Dobutamine, milrinone — acute low-output (cardiogenic) states, bridge to advanced therapy, or palliation

HF with mildly reduced or preserved EF (LVEF > 40%): diuretics for congestion, an SGLT2 inhibitor, and control of blood pressure, AF, and obesity. Finerenone, a nonsteroidal MRA, received US FDA approval in July 2025 for HF with LVEF ≥ 40% — monitor K⁺ and eGFR (hyperkalemia); contraindicated with strong CYP3A4 inhibitors.

Acute decompensated HF: IV loop diuretic, vasodilators (nitroglycerin) if blood pressure allows, inotropes only for low output.

Pregnancy

• ACE inhibitors, ARBs, ARNI, and direct renin inhibitors carry a boxed warning for fetal toxicity — stop as soon as pregnancy is detected; counsel on contraception.
• Ivabradine and vericiguat also cause fetal harm; vericiguat carries a boxed warning and requires a negative pregnancy test before starting.
• Spironolactone has antiandrogenic effects on a male fetus and is generally avoided; SGLT2 inhibitors are not recommended in the second and third trimesters or during breastfeeding.

Key contraindications

• ACE inhibitor/ARNI: history of angioedema; ARNI and ACE inhibitor must never be combined — allow a 36-hour washout when switching from an ACE inhibitor to ARNI (or back).
• Bilateral renal artery stenosis (RAAS inhibitors); do not combine ACE inhibitor + ARB + MRA as a triple regimen (hyperkalemia).
• Aliskiren with ACE inhibitor/ARB/ARNI in clients with diabetes: contraindicated.
• MRA: do not start if K⁺ ≥ 5.0 mEq/L (mmol/L) or eGFR ≤ 30 mL/min/1.73 m².
• Beta blockers: symptomatic bradycardia, second- or third-degree heart block without a pacemaker, cardiogenic shock, decompensated HF requiring inotropes; caution in asthma.
• SGLT2 inhibitors: not recommended in type 1 diabetes (DKA risk); hold at least 3 days before scheduled surgery (4 days for ertugliflozin) and during acute illness or fasting.
• Digoxin: ventricular fibrillation; caution in hypertrophic obstructive cardiomyopathy, AV block, Wolff–Parkinson–White syndrome with AF, and kidney impairment.
• Nitrates, vericiguat: never with PDE-5 inhibitors (sildenafil, tadalafil) — profound hypotension.

Interactions

• Potassium supplements, salt substitutes (potassium chloride), trimethoprim, NSAIDs + RAAS inhibitors/MRA → hyperkalemia and kidney injury.
• NSAIDs also cause sodium retention and blunt diuretics — avoid in HF.
• Loop diuretics + digoxin → hypokalemia increases digoxin toxicity. Loop diuretics + aminoglycosides → additive ototoxicity; + lithium → higher lithium levels.
• Amiodarone, verapamil, quinidine, clarithromycin raise digoxin levels (the digoxin dose is commonly reduced when amiodarone starts).
• Drugs that worsen HF — avoid: nondihydropyridine calcium channel blockers (diltiazem, verapamil) in HFrEF, thiazolidinediones (pioglitazone), most class I antiarrhythmics, dronedarone in advanced HF, cilostazol, and over-the-counter decongestants.

1. Assess before giving
   • Apical pulse for 1 full minute before digoxin and beta blockers. Digoxin is commonly held for an adult apical pulse < 60/min (or per the written parameter) and the provider notified; children have age-specific parameters
   • Blood pressure before RAAS inhibitors, ARNI, beta blockers, vasodilators; hold and notify for symptomatic hypotension or systolic BP below the ordered limit
   • Lung sounds, edema, jugular venous distension, and daily weight (same time, same scale, same clothing)
2. Laboratory monitoring

1. Administration
   • IV furosemide: give slowly (commonly no faster than about 4 mg/min for larger doses) to reduce ototoxicity; expect diuresis within about 5 minutes (IV) or 1 hour (oral); give oral doses in the morning (early afternoon for a second dose) to avoid nocturia
   • Beta blockers: start low and increase every 2 weeks or so; temporary fatigue or slight weight gain is expected early
   • Digoxin: confirm the dose (micrograms versus milligrams — a common error); IV digoxin is given slowly over at least 5 minutes
   • Dobutamine/milrinone: infusion pump, continuous ECG and BP monitoring, correct potassium and magnesium first
2. Fall prevention — orthostatic hypotension with diuretics and vasodilators; rise slowly
3. Watch for angioedema after ACE inhibitor or ARNI doses — swelling of lips, tongue, or throat is an airway emergency

• Weigh every morning after voiding and before breakfast; report a gain of 2–3 lb (about 1 kg) in 1 day or 5 lb (about 2 kg) in 1 week
• Take the diuretic in the morning; expect more urination; change position slowly
• Do not use salt substitutes or potassium supplements unless prescribed while taking ACE inhibitors, ARBs, ARNI, or MRAs; eat potassium-rich foods only as advised if taking a loop diuretic
• ACE inhibitor: a dry cough is common — report it, do not stop the drug on your own; go to emergency care for swelling of the face, lips, tongue, or throat
• Never stop a beta blocker suddenly (risk of angina, dysrhythmia, MI)
• Digoxin: count the pulse as taught; report loss of appetite, nausea, vomiting, blurred or yellow-green vision, or a slow or irregular pulse; do not take antacids at the same time; use one brand consistently
• SGLT2 inhibitor: genital hygiene; stop and call the provider during vomiting, poor intake, or before surgery; report nausea, abdominal pain, or rapid breathing even if glucose is normal
• Avoid NSAIDs and decongestants; check with the provider before any new over-the-counter or herbal product
• Pregnancy-capable clients on RAAS drugs, ivabradine, or vericiguat: use effective contraception and report pregnancy immediately

Digoxin toxicity (narrow therapeutic index)

• Early signs: anorexia, nausea, vomiting, abdominal pain; then fatigue, confusion (especially in older adults), visual disturbances (blurred vision, yellow-green halos)
• Cardiac: bradycardia, AV block, premature ventricular contractions, bidirectional or ventricular tachycardia — almost any dysrhythmia
• Risk factors: hypokalemia, hypomagnesemia, hypercalcemia, reduced kidney function, older age, hypothyroidism, and interacting drugs
• Acute overdose tends to cause hyperkalemia (a marker of severity); chronic toxicity is often accompanied by hypokalemia
• Management: hold digoxin, obtain level, potassium, magnesium, creatinine, continuous ECG; correct low potassium and magnesium; digoxin immune Fab is the antidote for life-threatening dysrhythmias, severe hyperkalemia, or very high levels. After Fab, measured total digoxin levels are unreliable; watch for hypokalemia and return of HF or rapid AF

Other toxicity

• RAAS inhibitor/MRA → hyperkalemia: peaked T waves, weakness — treat per hyperkalemia protocol (see IV Fluids and Electrolyte Replacement)
• Angioedema → stop the drug permanently, protect the airway; antihistamines and epinephrine help less in bradykinin-mediated (ACE inhibitor) angioedema
• Diuretic overdiuresis → hypotension, dehydration, hypokalemia, acute kidney injury
• Beta blocker overdose → bradycardia, hypotension, hypoglycemia; treated with atropine, IV fluids, glucagon, high-dose insulin therapy, vasopressors

• HFrEF four pillars: ARNI/ACEI/ARB + beta blocker + MRA + SGLT2 inhibitor
• ACE inhibitor → dry cough, angioedema, hyperkalemia; 36-hour washout between ACE inhibitor and ARNI
• ACE inhibitors, ARBs, ARNI → contraindicated in pregnancy (boxed fetal toxicity)
• Only carvedilol, metoprolol succinate, bisoprolol are the evidence-based HF beta blockers; never stop abruptly
• MRA → hyperkalemia; not started if K⁺ ≥ 5.0 or eGFR ≤ 30; spironolactone → gynecomastia
• SGLT2 inhibitor → euglycemic DKA; hold 3 days before surgery
• Loop diuretic → hypokalemia, ototoxicity with rapid IV push
• Digoxin → apical pulse 1 minute; hold if < 60/min; HF target level about 0.5–0.9 ng/mL
• Digoxin toxicity → anorexia, nausea, vomiting first, then vision changes; hypokalemia raises risk; antidote digoxin immune Fab
• Nitrates or vericiguat + PDE-5 inhibitor → severe hypotension