What are the four pillars of heart failure?

The Four Pillars of Heart Failure with Reduced Ejection Fraction

The four pillars of heart failure with reduced ejection fraction (HFrEF) are: (1) Renin-Angiotensin-Aldosterone System inhibitors (RAAS inhibitors, including ACE inhibitors, ARBs, or ARNI), (2) Beta-blockers, (3) Mineralocorticoid receptor antagonists (MRAs), and (4) Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors). 1

Core Disease-Modifying Therapy

This four-pillar framework represents the foundational pharmacological treatment for all patients with HFrEF, as these medications have demonstrated mortality and morbidity benefits in large randomized controlled trials. 1, 2

The Four Pillars Explained:

1. RAAS Inhibitors (ACE-I/ARB/ARNI)

• ACE inhibitors should be used in all patients with significantly reduced left ventricular ejection fraction unless contraindicated, with Class I, Level A evidence. 1
• Angiotensin receptor-neprilysin inhibitors (ARNI) are preferred over ACE inhibitors when tolerated, as they provide superior outcomes. 2, 3
• Angiotensin receptor blockers (ARBs) serve as alternatives for patients who cannot tolerate ACE inhibitors. 4

2. Beta-Blockers

• Beta-blockers should be used in all patients with reduced ejection fraction to prevent symptomatic heart failure and reduce mortality. 4, 3
• These medications have Class I, Level A evidence for HFrEF treatment. 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Aldosterone receptor antagonists should be used in patients with NYHA class II through IV heart failure who have an ejection fraction of 35% or less. 4
• Monitoring for hyperkalemia and renal insufficiency is essential when using MRAs. 4

4. Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i)

• SGLT2 inhibitors significantly reduce cardiovascular and all-cause mortality irrespective of diabetes status. 3
• This is the most recent addition to the four-pillar framework, representing a major therapeutic advance. 1, 2

Implementation Strategy

Initiation Approach:

• The 2023 ESC Guidelines recommend an intensive strategy of initiation and rapid up-titration of all four pillars before hospital discharge for newly diagnosed HFrEF patients. 5
• Early concomitant administration and up-titration of all four pillars within 1 month significantly reduces heart failure hospitalization risk compared to conventional stepwise approaches. 5
• All four medications should be started simultaneously when possible, rather than sequentially, to maximize benefit during the vulnerable post-diagnosis period. 5

Dosing Strategy:

• Target doses should be those proven effective in randomized controlled trials for each medication class. 1
• Diuretics should be added as needed for fluid management but are not considered part of the four pillars as they provide symptom relief without mortality benefit. 4, 3

Important Clinical Considerations

Key Differences Between Guidelines:

• The ACC/AHA/HFSA guidelines explicitly name the "four pillars" framework, while ESC guidelines describe the same medications without using this specific terminology. 1
• Both guideline sets agree on the core medications, with only minor differences in level of evidence assignments. 1

Common Pitfalls to Avoid:

• Do not delay initiation of any pillar while waiting to optimize another—simultaneous initiation is preferred. 5
• Before introducing ACE inhibitors or ARNI, review diuretic dosing and avoid excessive diuresis to minimize hypotension risk. 4
• When starting MRAs, discontinue any potassium-sparing diuretics to avoid hyperkalemia. 1
• Monitor renal function and electrolytes closely, especially when combining RAAS inhibitors with MRAs. 4

Monitoring Requirements:

• Measure blood urea nitrogen, creatinine, potassium, and sodium daily during IV therapy and when adjusting RAAS-affecting medications. 4
• Reassess symptoms, health status, and left ventricular function after initiating disease-modifying therapies. 2

Beyond the Four Pillars

Additional Therapies for Specific Populations:

• Ivabradine has a role in patients with persistent symptoms despite optimal four-pillar therapy who remain in sinus rhythm with heart rate ≥70 bpm. 3
• Hydralazine/isosorbide dinitrate benefits certain patients, particularly self-identified Black patients with persistent symptoms. 3
• Vericiguat reduces heart failure hospitalization in high-risk patients with recent worsening HF, representing a potential "fifth pillar." 3, 6

Device Therapies:

• Cardiac resynchronization therapy benefits patients with interventricular dyssynchrony. 3
• Implantable cardiac defibrillators are indicated for patients with LVEF ≤30% for primary prevention of sudden cardiac death. 7

The four-pillar framework represents the current standard of care for HFrEF, with strong evidence supporting simultaneous initiation and rapid optimization to improve both mortality and morbidity outcomes. 1, 2, 5