What are the four pillars of heart failure management in patients with a history of hypertension, diabetes, or coronary artery disease?

The Four Pillars of Heart Failure Management

For patients with heart failure and reduced ejection fraction (HFrEF), particularly those with hypertension, diabetes, or coronary artery disease, the four foundational medication classes are: (1) ACE inhibitors/ARBs or ARNi, (2) beta-blockers, (3) mineralocorticoid receptor antagonists (MRAs), and (4) SGLT2 inhibitors—all of which should be initiated and optimized to reduce mortality and prevent disease progression. 1, 2, 3

The Four Pillars Defined

Pillar 1: ACE Inhibitors/ARBs or ARNi

• ACE inhibitors are first-line therapy for all patients with reduced left ventricular systolic function, regardless of symptom severity, to prevent symptomatic heart failure and reduce mortality. 2
• ARBs serve as alternatives for patients intolerant to ACE inhibitors (typically due to cough or angioedema). 1, 4
• Angiotensin receptor-neprilysin inhibitors (ARNi) represent an advanced option that can replace ACE inhibitors/ARBs in appropriate patients with HFrEF. 1, 3
• This pillar carries Class I recommendation with Level A evidence across all major guidelines. 2

Pillar 2: Beta-Blockers

• Beta-blockers should be used in all patients with stable heart failure and reduced ejection fraction in NYHA class II-IV, unless contraindicated. 2
• They prevent symptomatic worsening and improve survival when combined with ACE inhibition. 5
• 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
• Evidence-based beta-blockers must be used specifically (not all beta-blockers are equivalent). 4

Pillar 3: Mineralocorticoid Receptor Antagonists (MRAs)

• Aldosterone receptor antagonists are recommended for patients with NYHA class II through IV heart failure who have an ejection fraction of 35% or less. 2
• Spironolactone is specifically indicated in patients with recent or current class IV symptoms, preserved renal function, and normal potassium concentration. 1
• Careful monitoring for hyperkalemia and renal insufficiency is essential, particularly when combined with ACE inhibitors. 2

Pillar 4: SGLT2 Inhibitors

• SGLT2 inhibitors (dapagliflozin or empagliflozin) are foundational therapy for HFrEF to reduce heart failure hospitalizations and death. 5
• This represents the most recent addition to guideline-directed medical therapy, with strong evidence supporting mortality and morbidity benefits. 1, 3
• These agents provide benefit regardless of diabetes status. 6

Implementation Strategy for High-Risk Patients

Patients with Hypertension

• Control of systolic and diastolic hypertension in patients with HF is a Class I recommendation with Level A evidence. 1
• Aggressive blood pressure control with a goal of less than 130/85 mm Hg is particularly critical in diabetic patients with hypertension. 7
• The four-pillar medications themselves provide blood pressure control while addressing the underlying heart failure pathophysiology. 2

Patients with Diabetes

• All four pillars should be initiated as diabetes is a major risk factor for heart failure progression. 7
• Patients with type 2 diabetes are more likely to benefit from the complete four-pillar regimen. 8
• SGLT2 inhibitors provide dual benefit for glycemic control and heart failure management. 6

Patients with Coronary Artery Disease

• Statins should be used in patients with recent or remote history of MI or acute coronary syndrome to prevent symptomatic heart failure and adverse cardiovascular events (Class I, Level A). 4
• Beta-blockers are particularly important in post-MI patients with LVEF ≤40% to reduce mortality. 4
• Nitrates and beta-blockers (in conjunction with diuretics) are recommended for treatment of angina in patients with HF. 1

Essential Adjunctive Therapy

Diuretics (Not a "Pillar" but Essential)

• Diuretics are essential for symptomatic treatment when fluid overload is present and should be used in patients with evidence or history of fluid retention. 2
• They provide rapid improvement of dyspnea and increased exercise tolerance. 2
• Diuretics should always be administered in combination with ACE inhibitors, not as monotherapy. 2

Sequencing and Initiation

Rapid Implementation Approach

• All four pillars should be initiated as soon as possible after diagnosis, not sequentially over months. 3, 6
• Start low and titrate up for each medication class while monitoring blood pressure, renal function, and electrolytes 1-2 weeks after each dose increment. 2
• Do not wait for one medication to be optimized before starting the next pillar. 6

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. 2
• Assess symptoms and functional capacity with each medication adjustment. 4

Critical Medications to AVOID

Contraindicated Agents

• Thiazolidinediones should not be used in patients with LVEF <50% as they increase heart failure risk and hospitalizations. 5, 4
• Nondihydropyridine calcium channel blockers (diltiazem, verapamil) with negative inotropic effects should be avoided in patients with LVEF <50%. 5, 4
• NSAIDs and coxibs should be avoided as they interfere with ACE inhibitor efficacy and worsen fluid retention. 1, 2
• Class I anti-arrhythmic agents should be avoided. 1

Common Pitfalls and How to Avoid Them

Underutilization

• Only 0.6% of patients in real-world registries receive the complete four-pillar treatment, representing a massive treatment gap. 8
• Beta-blockers are most frequently prescribed (74%) while SGLT2 inhibitors are least common (9%), despite their strong mortality benefit. 8

Inappropriate Withholding

• Do not withhold neurohormonal antagonists (ACE inhibitors, beta-blockers) in stable patients due to concerns about tolerability—these are mortality-reducing therapies. 2
• Patients should have no or minimal fluid retention before initiating beta-blockers, but this should not delay ACE inhibitor or SGLT2 inhibitor initiation. 1

Medication Interactions

• Avoid 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

Titration Errors

• Patients with advanced heart failure may be less tolerant of neurohormonal antagonism, requiring careful titration rather than abandonment of therapy. 2
• Review and adjust diuretic and vasodilator doses when starting ACE inhibitors to minimize hypotensive effects. 4