What is the initial management for heart failure with reduced ejection fraction (HFrEF)?

Initial Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

The initial management of HFrEF should include four foundational medication classes: angiotensin receptor-neprilysin inhibitor (ARNi) or angiotensin-converting enzyme inhibitor (ACEi)/angiotensin receptor blocker (ARB), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). 1

Core Medication Classes for HFrEF

First-Line Medications (Start Simultaneously)

1. Renin-Angiotensin System Inhibition

   • ARNi (Sacubitril/Valsartan): Preferred first-line therapy for NYHA class II-III symptoms 1
   • ACEi: Use when ARNi is not feasible 1
   • ARB: Alternative if patient is intolerant to ACEi (cough, angioedema) 1

2. Beta-Blockers

   • Evidence-based options: carvedilol, metoprolol succinate, or bisoprolol 1
   • Start at low doses and titrate gradually

3. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone or eplerenone
   • Monitor potassium and renal function

4. SGLT2 Inhibitors

   • Dapagliflozin or empagliflozin
   • Unique advantage: No dose titration required and minimal effect on blood pressure, heart rate, or potassium 1

Symptom Management

• Diuretics: Titrate based on congestion status
• Digoxin: Consider for symptom control, particularly with atrial fibrillation 2

Implementation Strategy

Modern Approach to Initiation

• Start all four medication classes simultaneously at low doses rather than sequential addition and full titration of each drug 1
• Begin with low doses and gradually uptitrate as tolerated
• Target doses should be goals, but even lower doses provide significant benefit 3

Practical Titration Algorithm

1. Start with low doses of all four medication classes
2. Assess vital signs, symptoms, and laboratory values every 2-4 weeks
3. Uptitrate one medication at a time based on:
   • If hypotensive: Prioritize beta-blocker titration
   • If hyperkalemic: Adjust MRA dose
   • If renal dysfunction: Adjust ACEi/ARB/ARNi dose

Special Considerations

For Specific Patient Populations

• African American patients: Consider hydralazine-isosorbide dinitrate in addition to standard therapy 1
• Patients with severe renal impairment: Start with half the usual dose of ACEi/ARB/ARNi 4
• Patients with moderate hepatic impairment: Start with half the usual dose of ACEi/ARB/ARNi 4

Common Pitfalls to Avoid

• Underdosing: Many patients remain on suboptimal doses; however, even lower doses provide mortality benefit 3
• Clinical inertia: Delaying addition of proven therapies while waiting for full titration of initial drugs 1
• Inappropriate discontinuation: Temporary worsening of renal function or mild hypotension should not lead to permanent discontinuation
• NSAIDs: Avoid as they can worsen renal function and counteract HF medication benefits 4

When to Consider Advanced Therapies

• Persistent symptoms despite optimal medical therapy
• Consider device therapy:
  • ICD for primary prevention in appropriate candidates
  • Cardiac resynchronization therapy for QRS >120ms with NYHA class II-IV symptoms 1
• Refer to HF specialist for patients with advanced symptoms or difficulty tolerating medications 1

Monitoring Response

• Assess clinical symptoms, fluid status, and vital signs
• Monitor renal function and electrolytes, particularly potassium
• Consider natriuretic peptide levels to guide therapy
• Evaluate for improvement in ejection fraction (patients with improved EF >40% should continue HFrEF treatment) 1

The evidence strongly supports early initiation of all four medication classes to reduce mortality and morbidity in HFrEF patients, with dose optimization as a secondary but important goal.