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

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

Quadruple therapy with SGLT2 inhibitors, beta-blockers, renin-angiotensin system inhibitors (preferably ARNI), and mineralocorticoid receptor antagonists is the recommended initial treatment for heart failure with reduced ejection fraction to significantly reduce mortality and hospitalizations. 1

First-Line Medications

The cornerstone of HFrEF management consists of four medication classes that should be initiated and titrated to target doses:

1. Renin-Angiotensin System Inhibitors:

   • ARNI (Sacubitril/Valsartan): First-line option for HFrEF to reduce cardiovascular death and hospitalization 2
     • Starting dose: 24/26 mg–49/51 mg twice daily
     • Target dose: 97/103 mg twice daily 3
   • ACE Inhibitors (if ARNI not tolerated/available):
     • Enalapril: 2.5 mg twice daily → 10-20 mg twice daily
     • Lisinopril: 2.5-5 mg daily → 20-40 mg daily
     • Ramipril: 1.25 mg daily → 10 mg daily 3
   • ARBs (if ACE inhibitors not tolerated):
     • Candesartan: 4-8 mg daily → 32 mg daily
     • Valsartan: 40 mg twice daily → 160 mg twice daily 3

2. Beta-Blockers:

   • Bisoprolol: 1.25 mg once daily → 10 mg once daily
   • Carvedilol: 3.125 mg twice daily → 25-50 mg twice daily
   • Metoprolol succinate: 12.5-25 mg daily → 200 mg daily 3, 1

3. Mineralocorticoid Receptor Antagonists (MRAs):

   • Spironolactone: 12.5-25 mg daily → 25-50 mg daily
   • Eplerenone: 25 mg daily → 50 mg daily 3, 1

4. SGLT2 Inhibitors:

   • Dapagliflozin: 10 mg daily
   • Empagliflozin: 10 mg daily 3, 1

Implementation Strategy

1. Initiation Sequence:

   • Start with low doses of an ARNI (or ACE inhibitor if ARNI unavailable) and a beta-blocker
   • Add MRA within 1-2 weeks if no contraindications
   • Add SGLT2 inhibitor once other medications are established
   • Titrate all medications to target doses as tolerated

2. Diuretics:

   • Use loop diuretics as needed for congestion symptoms
   • Adjust dose based on volume status

Special Considerations

• Monitoring Requirements:

  • Check renal function and potassium before initiation and 1-2 weeks after starting therapy or dose changes 1
  • Monitor blood pressure, including postural changes
  • Watch for signs of angioedema, particularly with ACE inhibitors and ARNIs 1

• Titration Approach:

  • Beta-blockers should be initiated with a "start low, go slow" approach 1
  • Titrate slowly, monitoring for worsening heart failure, hypotension, or bradycardia

• Contraindications:

  • Avoid NSAIDs and COX-2 inhibitors in all heart failure patients 1
  • Avoid thiazolidinediones (glitazones) 1
  • Avoid combining ARB with ACE inhibitor and MRA due to increased risk of renal dysfunction and hyperkalemia 1
  • Avoid diltiazem/verapamil in HFrEF patients 1

Evidence for Mortality Benefit

• Beta-blockers reduce mortality by at least 20% 1
• MRAs reduce mortality by at least 20% 1
• ARNI (sacubitril/valsartan) has demonstrated superior outcomes compared to enalapril in reducing cardiovascular mortality 4
• SGLT2 inhibitors have shown a reduction in cardiovascular death and heart failure hospitalization 3

Patient Education and Follow-up

• Implement daily weight monitoring with an action plan for weight gain greater than 2 kg in 3 days 1
• Educate on symptom recognition, medication adherence, and when to contact healthcare providers
• Schedule frequent follow-ups, especially after initiation or titration of therapy

By implementing this comprehensive medication regimen early and titrating to target doses, you can significantly improve outcomes for patients with HFrEF, including reduced mortality and hospitalization rates.