What are the four medications for CHF? Exploring the Pillars of Modern Heart Failure Treatment

October 16, 2025 •

4 min read

According to the CDC, approximately 6.2 million adults in the United States live with heart failure, a number that is expected to rise. For patients with heart failure with reduced ejection fraction (HFrEF), treatment has evolved significantly with the introduction of four core medication classes, often referred to as the “four pillars” of therapy. This guideline-directed medical therapy aims to extend life and improve quality of life by targeting different mechanisms that cause the heart to fail.

Quick Summary

Modern heart failure treatment often relies on four key medication classes: ARNIs (or ACEi/ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors. This comprehensive regimen slows disease progression, reduces symptoms, and decreases hospitalizations and mortality. Diuretics are also used for managing fluid retention.

Key Points

The Four Pillars: The core drug classes for heart failure with reduced ejection fraction (HFrEF) are RAS inhibitors (ARNI/ACEi/ARB), beta-blockers, MRAs, and SGLT2 inhibitors.
ARNI (Sacubitril/Valsartan): Often the preferred first-line therapy, this combination drug has shown superior benefits in reducing hospitalizations and death compared to older RAS inhibitors.
Beta-Blockers (e.g., carvedilol, metoprolol): These slow the heart rate and reduce the heart's workload, blocking harmful stress hormones and improving long-term heart function.
Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone and eplerenone block aldosterone, a hormone that causes fluid retention and cardiac fibrosis, but require monitoring for high potassium levels.
SGLT2 Inhibitors (e.g., dapagliflozin, empagliflozin): These drugs, originally for diabetes, also reduce hospitalizations and cardiovascular death in heart failure patients by helping the body excrete excess sodium and water.
Diuretics for Symptom Control: 'Water pills' like furosemide are crucial for relieving symptoms like swelling and breathlessness caused by fluid buildup, but do not offer the same mortality benefits as the four pillar drugs.
Personalized Treatment: A healthcare provider determines the best combination of these medications, starting with low doses and slowly increasing them while closely monitoring for side effects and drug interactions.

The Four Pillars of Heart Failure Pharmacotherapy

Recent guidelines from major cardiology organizations now recommend four core foundational medication classes for patients with heart failure with reduced ejection fraction (HFrEF). These “four pillars” work synergistically to provide long-term benefits by interrupting the complex neurohormonal processes that contribute to the progression of heart failure.

1. Renin-Angiotensin System (RAS) Inhibitors

The renin-angiotensin system plays a major role in heart failure by causing blood vessels to constrict and encouraging the body to retain salt and water, increasing the workload on the heart. There are three main options for inhibiting this system:

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs): The combination drug sacubitril/valsartan (Entresto) is often the preferred first-line therapy for many patients with HFrEF. It works by blocking the angiotensin II receptor while also preventing the breakdown of natriuretic peptides, which widen blood vessels and decrease sodium retention. Studies show it is superior to older therapies at reducing hospitalizations and death.
Angiotensin-Converting Enzyme (ACE) Inhibitors: These drugs block the enzyme that converts angiotensin I to the potent vasoconstrictor angiotensin II. By dilating blood vessels and lowering blood pressure, ACE inhibitors reduce the strain on the heart. Examples include lisinopril (Prinivil, Zestril) and enalapril (Vasotec).
Angiotensin II Receptor Blockers (ARBs): ARBs offer similar benefits to ACE inhibitors by blocking angiotensin II receptors. They are typically used for patients who cannot tolerate the cough associated with ACE inhibitors. Examples include valsartan (Diovan) and losartan (Cozaar).

2. Beta-Blockers

Beta-blockers work by countering the effects of chronic sympathetic nervous system overstimulation, which is detrimental to the heart over time. By blocking beta-adrenergic receptors, these medications help slow the heart rate and decrease blood pressure, reducing the heart’s workload.

Mechanism: Beta-blockers prevent the damaging effects of catecholamines (like norepinephrine) on the heart muscle, preventing ventricular remodeling and fibrosis.
Key Examples: Not all beta-blockers are approved for heart failure. The most-studied options with proven mortality benefits are carvedilol (Coreg), bisoprolol (Zebeta), and metoprolol succinate (Toprol-XL).
Important Considerations: Therapy should be initiated at a low dose and carefully titrated up. It is crucial for patients to not stop these medications abruptly, as this can worsen heart failure.

3. Mineralocorticoid Receptor Antagonists (MRAs)

MRAs, also known as aldosterone antagonists, block the harmful effects of the hormone aldosterone, which can cause fluid retention and heart fibrosis. These are generally used in combination with other heart failure medications.

Mechanism: MRAs block aldosterone receptors in the kidneys and heart, promoting sodium and water excretion while retaining potassium. This helps reduce blood pressure and congestion.
Key Examples: Spironolactone (Aldactone) and eplerenone (Inspra) are the two primary MRAs used.
Monitoring: Given their potassium-retaining effect, patients on MRAs require regular blood tests to monitor potassium levels and kidney function.

4. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

Originally developed for type 2 diabetes, SGLT2 inhibitors have been shown to have a significant and rapid benefit for patients with heart failure, regardless of diabetes status.

Mechanism: These drugs inhibit the reabsorption of glucose and sodium in the kidneys, leading to increased excretion in the urine. This reduces fluid volume, blood pressure, and strain on the heart.
Key Examples: Dapagliflozin (Farxiga) and empagliflozin (Jardiance) are approved for heart failure.
Benefits: Studies show SGLT2 inhibitors reduce hospitalizations and cardiovascular death in patients with HFrEF and HFpEF.

Diuretics: Managing the Symptoms

While the four pillars focus on long-term disease modification, diuretics are essential for immediate symptom relief. Often called “water pills,” diuretics help the body get rid of excess fluid and sodium through urination. This reduces swelling in the legs, ankles, and abdomen, as well as congestion in the lungs, making breathing easier.

Mechanism: Different classes of diuretics work in different parts of the kidney to promote diuresis. Loop diuretics, such as furosemide (Lasix), are very effective at reducing significant fluid overload.
Note: While they significantly improve comfort and quality of life, diuretics alone do not offer the same long-term survival benefits as the four pillar drugs. They are a critical part of the overall treatment plan, but they address symptoms rather than the underlying disease progression.

Comparison of Core Heart Failure Medications


Medication Class	Example Drugs	Primary Mechanism	Key Benefits	Common Side Effects
ARNI	sacubitril/valsartan (Entresto)	Blocks angiotensin II receptors and enhances natriuretic peptides	Reduces mortality and hospitalization; improves heart function	Hypotension, dizziness, cough, elevated creatinine
Beta-Blockers	carvedilol, bisoprolol, metoprolol succinate	Blocks beta-adrenergic receptors; decreases heart rate and blood pressure	Reduces mortality and hospitalization; improves heart function	Fatigue, slow heart rate, low blood pressure
MRAs	spironolactone, eplerenone	Blocks aldosterone receptors	Reduces mortality and hospitalization; manages fluid balance	Hyperkalemia (high potassium), gynecomastia (spironolactone)
SGLT2 Inhibitors	dapagliflozin, empagliflozin	Increases excretion of glucose and sodium in urine	Reduces mortality and hospitalization (even in non-diabetics)	Genital mycotic infections, potential dehydration
Diuretics	furosemide, bumetanide	Increases urination to remove excess fluid	Eases symptoms of fluid retention and breathlessness	Dehydration, electrolyte imbalances (low potassium), dizziness

Conclusion: A Multi-faceted Approach to Care

The pharmacological treatment of congestive heart failure has advanced significantly, moving from symptom management to a strategy of neurohormonal blockade that improves long-term outcomes. The four pillar approach, incorporating an ARNI (or ACEi/ARB), a beta-blocker, an MRA, and an SGLT2 inhibitor, is now the cornerstone of guideline-directed medical therapy for HFrEF. While diuretics remain essential for controlling fluid buildup and providing symptomatic relief, the powerful combination of the four foundational drug classes offers the best chance for reducing hospitalizations and mortality. Successful management requires a personalized approach, close monitoring by a healthcare provider, and vigilant adherence to the prescribed regimen to ensure the best possible quality of life for patients.

Further Resources

For more in-depth information, the Heart Failure Society of America provides comprehensive patient education on various heart failure medications.

Heart Failure Society of America

Frequently Asked Questions

The four foundational medication classes for heart failure with reduced ejection fraction (HFrEF) are: RAS inhibitors (specifically ARNIs like sacubitril/valsartan, or ACE inhibitors/ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors.

Yes, while diuretics are an essential part of heart failure management to control symptoms like fluid retention, they do not offer the same proven mortality benefits as the four foundational medication classes. Their primary role is symptomatic relief.

ARNIs (Angiotensin Receptor-Neprilysin Inhibitors), like sacubitril/valsartan, are a combination therapy that has been shown to be superior to ACE inhibitors in reducing cardiovascular mortality and hospitalizations in HFrEF patients. They have a dual mechanism of action that provides greater benefit.

Heart failure is a complex condition involving multiple body systems. By taking several different medications from the four core classes, each targeting a specific pathway, the patient receives comprehensive treatment that provides both symptomatic relief and long-term survival benefits.

Common side effects of beta-blockers can include fatigue, dizziness, and a slow heart rate. It is important to remember these often lessen over time, and abrupt discontinuation can be harmful.

SGLT2 inhibitors, such as dapagliflozin and empagliflozin, were originally for diabetes but are now recognized as one of the four pillars of heart failure therapy. They work by causing the kidneys to excrete excess salt and water, reducing the heart's workload and lowering the risk of hospitalization.

If you miss a dose, follow your healthcare provider's instructions. Do not take a double dose to catch up. Consistent medication adherence is critical for controlling heart failure, so discuss any challenges you have with your provider to find a manageable routine.