What is the preferred treatment for heart failure with reduced ejection fraction (HFrEF)?

Preferred Treatment for Heart Failure with Reduced Ejection Fraction (HFrEF)

The preferred treatment for heart failure with reduced ejection fraction (HFrEF) is quadruple therapy consisting of an ARNI (or ACE inhibitor/ARB), beta-blocker, mineralocorticoid receptor antagonist (MRA), and SGLT2 inhibitor, which provides the largest reduction in cardiovascular death and heart failure hospitalization. 1

Foundation Therapy (First-Line Treatments)

ACE Inhibitors/ARBs/ARNIs

• Start with low doses of ACE inhibitors (e.g., enalapril) and titrate to target doses used in clinical trials 1
• Monitor blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment, at 3 months, and every 6 months thereafter 1
• Consider ARBs (candesartan or valsartan) if patient is intolerant to ACE inhibitors due to cough or angioedema 2
• Sacubitril/valsartan (ARNI) may be used instead of an ACE inhibitor or ARB in patients with chronic symptomatic HFrEF class II or III to further reduce morbidity and mortality 2, 3

Beta-Blockers

• Should be initiated along with ACE inhibitors in clinically stable patients (NYHA class II-IV) 1
• Options with proven mortality benefit include:
  • Carvedilol
  • Metoprolol succinate (extended-release)
  • Bisoprolol 1, 2
• Up-titrating beta-blockers to target dose is associated with greater mortality reduction than up-titrating ACE inhibitors/ARBs 4

Additional Therapies

Mineralocorticoid Receptor Antagonists (MRAs)

• Add MRAs (spironolactone or eplerenone) for patients who remain symptomatic despite ACE inhibitor and beta-blocker therapy 1
• Indicated for treatment of NYHA Class III-IV heart failure with reduced ejection fraction to increase survival, manage edema, and reduce hospitalizations 5
• Use in patients with serum creatinine ≤2.5 mg/dL in men and ≤2.0 mg/dL in women, and serum potassium <5.0 mEq/L 2

SGLT2 Inhibitors

• Dapagliflozin or empagliflozin are recommended for HFrEF to reduce the risk of heart failure hospitalization and cardiovascular death 1, 6
• Can be used in addition to current therapies and provide benefits beyond cardiovascular system 6, 3

Diuretics

• Loop diuretics (e.g., furosemide) are first-line drugs for patients with HFrEF and volume overload 2
• Adjust dose to achieve and maintain euvolemia (patient's "dry weight") with lowest achievable dose 7
• Patients can be trained to self-adjust diuretic dose based on symptoms/signs of congestion and daily weight measurements 7, 1

Treatment Algorithm

1. Initial Therapy: Start simultaneously with:

   • ACE inhibitor (or ARB if intolerant) AND
   • Beta-blocker (carvedilol, metoprolol succinate, or bisoprolol)
   • Diuretics if fluid retention is present

2. Optimization: Titrate both medications to target doses

3. Add-on Therapy: For patients who remain symptomatic:

   • Add MRA (spironolactone or eplerenone)
   • Consider switching ACE inhibitor/ARB to ARNI (sacubitril/valsartan)
   • Add SGLT2 inhibitor (dapagliflozin or empagliflozin)

4. Device Therapy: Consider for appropriate patients:

   • ICD for patients with LVEF ≤35% and NYHA Class II-III symptoms with >1 year life expectancy
   • CRT for patients with LVEF ≤35%, QRS duration ≥150ms with LBBB morphology 1

Monitoring and Practical Considerations

• Monitor electrolytes and renal function 1-2 weeks after each dose increase, at 3 months, and every 6 months thereafter 1
• Patients should weigh themselves daily and increase diuretic dose if weight increases by 1.5-2.0 kg over 2 days 1
• Avoid NSAIDs due to risk of worsening renal function and fluid retention 1
• Avoid most calcium channel blockers in HFrEF due to negative inotropic effects 7
• Best outcomes are observed in patients attaining guideline-recommended target doses for both ACE inhibitor/ARB and beta-blockers, though this is rarely achieved in practice 4

Common Pitfalls to Avoid

• Underdosing of foundation therapies: Only 14% of patients achieve ≥50% of guideline-recommended target doses for both ACE inhibitor/ARB and beta-blocker 4
• Inadequate monitoring of electrolytes and renal function, especially when using combination therapy
• Failure to adjust diuretics appropriately, leading to either fluid overload or dehydration
• Using calcium channel blockers with negative inotropic effects in HFrEF patients
• Not considering device therapy in eligible patients

By following this comprehensive approach to HFrEF management, clinicians can significantly reduce mortality, hospitalizations, and improve quality of life for patients with heart failure.