Congestive heart failure (CHF) is a complex clinical syndrome where the heart is unable to pump blood effectively to meet the body’s needs. It may result from structural or functional cardiac disorders such as coronary artery disease, hypertension, or valvular disease. Management of CHF includes both pharmacological and non-pharmacological approaches aimed at improving survival and relieving symptoms.
This blog from Pharmacy Freak explains the classification, mechanisms, and uses of drugs for heart failure, especially suited for medical and pharmacy students preparing for exams
Table of Contents
What is Drugs for Congestive Heart Failure
Congestive heart failure refers to the failure of the heart to maintain adequate cardiac output and tissue perfusion despite normal or elevated filling pressures. It may be left-sided, right-sided, or both, and is classified as systolic or diastolic based on the ejection fraction.
Classification of Drugs for Congestive Heart Failure (KD Tripathi)
- Inotropic drugs –
- Cardiac glycosides: Digoxin, Ouabain
- Sympathomimetics: Dobutamine, Dopamine
- PDE 3 inhibitors: Inamrinone, Milrinone
- Diuretics –
- High ceiling: Furosemide, Bumetanide
- Thiazide-like: Hydrochlorothiazide, Metolazone, Xipamide
- Renin-angiotensin inhibitors –
- ACE inhibitors: Enalapril, Ramipril, others
- Angiotensin AT₁ receptor blockers: Losartan, Candesartan, others
- Vasodilators –
- Venodilators: Glyceryl trinitrate, Isosorbide dinitrate
- Arteriolar + venodilator: Sodium nitroprusside
- Arteriolar dilator: Hydralazine
- Aldosterone antagonists: Spironolactone, Eplerenone
- β–adrenergic blockers: Metoprolol, Bisoprolol, Nebivolol, Carvedilol
- Note:
PDE: Phosphodiesterase
ACE: Angiotensin Converting Enzyme
Classification (General)
Drugs used in CHF are classified into two major categories:
- Drugs that reduce mortality
- Drugs that relieve symptoms
a. Angiotensin-Converting Enzyme (ACE) Inhibitors
Mechanism: Block conversion of angiotensin I to II, reduce afterload and preload
Drugs: Enalapril, Lisinopril, Ramipril
Use: First-line in all symptomatic and asymptomatic patients with reduced ejection fraction
b. Angiotensin II Receptor Blockers (ARBs)
Mechanism: Block AT1 receptors, similar hemodynamic benefits to ACE inhibitors
Drugs: Losartan, Valsartan, Candesartan
Use: In patients intolerant to ACE inhibitors
c. Beta Blockers
Mechanism: Reduce sympathetic overactivity, heart rate, and myocardial oxygen demand
Drugs: Carvedilol, Bisoprolol, Metoprolol succinate
Use: Stable CHF with reduced ejection fraction; not initiated during acute decompensation
d. Mineralocorticoid Receptor Antagonists (MRAs)
Mechanism: Block aldosterone action in kidneys and myocardium
Drugs: Spironolactone, Eplerenone
Use: Class II-IV heart failure with reduced ejection fraction
e. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors
Mechanism: Induce glycosuria, reduce preload and afterload
Drugs: Dapagliflozin, Empagliflozin
Use: CHF with reduced EF, regardless of diabetic status
f. Angiotensin Receptor-Neprilysin Inhibitor (ARNI)
Mechanism: Valsartan-sacubitril combination enhances natriuretic peptides and suppresses RAAS
Use: Replaces ACEI/ARB in symptomatic heart failure with reduced EF
g. Ivabradine
Mechanism: Selective If current inhibitor in the SA node, reduces heart rate
Use: In patients with heart rate >70 bpm despite maximum beta-blocker dose
- Drugs that relieve symptoms
a. Diuretics
Mechanism: Promote salt and water excretion, reduce preload
Drugs: Furosemide, Torsemide, Bumetanide (loop diuretics)
Use: Acute decompensated heart failure, pulmonary congestion
Thiazide diuretics (e.g., Metolazone) may be added for synergy
b. Vasodilators
Mechanism: Reduce preload and/or afterload
Drugs: Hydralazine + Isosorbide dinitrate
Use: Especially in patients intolerant to ACEIs, preferred in African-American populations
c. Inotropes
Mechanism: Increase contractility of the myocardium
Drugs: Digoxin, Dobutamine, Dopamine
Use: Acute decompensated heart failure, atrial fibrillation with CHF
Digoxin is used chronically for rate control and symptom relief
d. Cardiac Glycosides
Drug: Digoxin
Mechanism: Inhibits Na+/K+ ATPase, increases intracellular calcium
Use: CHF with atrial fibrillation; no survival benefit but reduces hospitalization
Uses
- Heart failure with reduced ejection fraction (HFrEF) – ACEI or ARNI + Beta blocker + MRA
- Volume overload – Add loop diuretic
- Persistent symptoms – Consider digoxin or ivabradine
- Heart failure with preserved EF (HFpEF) – Symptomatic management, control of comorbidities
- Acute decompensated CHF – IV loop diuretics, inotropes, oxygen
Drug of Choice Highlights
- Chronic HFrEF – ARNI (Sacubitril + Valsartan)
- Diuretic of choice – Furosemide
- For African-American patients – Hydralazine + Isosorbide dinitrate
- Rate control in CHF with AF – Digoxin
- SGLT2 inhibitor – Dapagliflozin or Empagliflozin (preferred even in non-diabetics)
Side Effects
- ACE inhibitors – Cough, hyperkalemia, angioedema
- ARBs – Hyperkalemia, hypotension
- Beta blockers – Bradycardia, fatigue, worsening of acute CHF
- Spironolactone – Hyperkalemia, gynecomastia
- SGLT2 inhibitors – Genital infections, dehydration
- Diuretics – Hypokalemia, metabolic alkalosis, ototoxicity (with loop diuretics)
- Digoxin – Arrhythmias, visual disturbances, toxicity in renal impairment
Updated Clinical Pearls
- Beta blockers and ACE inhibitors should be initiated at low doses and titrated slowly in stable patients.
- ARNI has shown mortality benefit and is now preferred over ACE inhibitors in HFrEF.
- SGLT2 inhibitors are recommended for both diabetics and non-diabetics with HFrEF.
- Routine digoxin level monitoring is essential, especially in elderly or renally impaired patients.
- Diuretics offer symptom relief but do not reduce mortality and should not be used alone.
References
- Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 584–599
- Gupta S, Garg A. Review of Pharmacology. 15th ed. New Delhi: Jaypee Brothers Medical Publishers; 2023. p. 235–239
- Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Education; 2011. p. 693–714
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