What are the 4 pillars of heart failure management?

The 4 Pillars of Heart Failure Management

For patients with heart failure and reduced ejection fraction (HFrEF), the four pillars of pharmacological therapy are: (1) ACE inhibitors or angiotensin receptor neprilysin inhibitors (ARNIs), (2) beta-blockers, (3) mineralocorticoid receptor antagonists (MRAs), and (4) sodium-glucose co-transporter-2 (SGLT2) inhibitors. 1

The Four Foundational Drug Classes

Pillar 1: ACE Inhibitors or ARNIs

• ACE inhibitors are recommended as first-line therapy in all patients with reduced left ventricular systolic function, regardless of symptom severity 2.
• These agents carry a Class I recommendation with Level A evidence across all major guidelines 2.
• ACE inhibitors should be used in all patients with reduced ejection fraction to prevent symptomatic heart failure and reduce mortality, even without a history of myocardial infarction 3.
• For patients who cannot tolerate ACE inhibitors, angiotensin receptor blockers serve as an alternative 3.
• ARNIs (angiotensin receptor neprilysin inhibitors) represent an evolution of this pillar and are now preferred over ACE inhibitors when tolerated 1.

Pillar 2: Beta-Blockers

• Beta-blockers are recommended for all patients with stable heart failure and reduced ejection fraction in NYHA class II-IV, unless contraindicated 2.
• This recommendation carries Class I evidence with Level A support 2.
• Beta-blockers should be used in all patients with reduced ejection fraction to prevent symptomatic heart failure 3.
• In patients with left ventricular systolic dysfunction following acute myocardial infarction, long-term beta-blockade is recommended in addition to ACE inhibition to reduce mortality 2.

Pillar 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 3.
• Spironolactone is indicated for treatment of NYHA Class III-IV heart failure with reduced ejection fraction to increase survival, manage edema, and reduce hospitalization 4.
• This therapy requires careful monitoring for hyperkalemia and renal insufficiency 3.
• The evidence level varies slightly between guidelines (Level A vs. Level B) due to reliance on a single major trial (RALES), but the recommendation strength remains consistent 2.

Pillar 4: SGLT2 Inhibitors

• Sodium-glucose co-transporter-2 inhibitors represent the newest pillar and are now recommended for all patients with HFrEF 1.
• This class has been added to guidelines based on recent evidence demonstrating mortality and hospitalization benefits 1.

Essential Adjunctive Therapy: Diuretics

While not considered a "pillar" due to lack of mortality benefit, diuretics are essential for symptomatic treatment when fluid overload is present 2.

• Diuretics should be used in patients with evidence or history of fluid retention 3.
• They result in rapid improvement of dyspnea and increased exercise tolerance 2.
• Diuretics should always be administered in combination with ACE inhibitors 2.
• For hospitalized patients with significant fluid overload, intravenous loop diuretics should be initiated without delay, as early intervention improves outcomes 2.

Critical Implementation Principles

Sequencing and Initiation

• All four pillars should be initiated and optimized in patients with HFrEF, not just those with advanced symptoms 1.
• Treatment should continue all measures from earlier stages as patients progress (Stage A → B → C → D) 3.
• When starting ACE inhibitors, avoid excessive diuresis beforehand and consider evening dosing when supine to minimize blood pressure effects 2, 3.

Monitoring Requirements

• Check blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment, at 3 months, and subsequently at 6-month intervals 2.
• Monitor for hyperkalemia when using MRAs, particularly when combined with ACE inhibitors 3, 4.
• Daily monitoring of fluid intake/output, weight, and clinical signs is essential during acute decompensation 2.

Common Pitfalls to Avoid

• Do not withhold neurohormonal antagonists (ACE inhibitors, beta-blockers) in stable patients due to concerns about tolerability—these are mortality-reducing therapies 2.
• Avoid non-steroidal anti-inflammatory drugs (NSAIDs) in patients on ACE inhibitors, as they interfere with efficacy 2.
• Do not use thiazide diuretics when GFR is less than 30 mL/min, except synergistically with loop diuretics 2.
• Patients with advanced heart failure may be less tolerant of neurohormonal antagonism, as these compensatory mechanisms support circulatory homeostasis in advanced disease—careful titration is required 3.

Beyond the Four Pillars

For patients with worsening heart failure despite optimal four-pillar therapy, vericiguat (a soluble guanylate cyclase stimulator) may represent an emerging "fifth pillar", particularly in older and complex patients, reducing both hospitalizations and deaths 5.