What is the initial treatment regimen for Heart Failure with Reduced Ejection Fraction (HFrEF)?

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

The initial treatment regimen for HFrEF should include quadruple therapy with an SGLT2 inhibitor, beta-blocker, renin-angiotensin system inhibitor (preferably ARNI), and mineralocorticoid receptor antagonist to significantly reduce mortality and hospitalizations. 1

Core Medication Classes

1. Renin-Angiotensin System Inhibitors

• First choice: Sacubitril/Valsartan (ARNI)

  • Initial dose: 49/51 mg twice daily
  • Target dose: 97/103 mg twice daily 1
  • Superior to ACE inhibitors in reducing cardiovascular death and hospitalization 2

• Alternative if ARNI not tolerated or available: ACE inhibitor or ARB

  • ACE inhibitor options:
    • Lisinopril: 2.5-5 mg once daily → 20-40 mg once daily
    • Enalapril: 2.5 mg twice daily → 10-20 mg twice daily
    • Ramipril: 1.25-2.5 mg once daily → 10 mg once daily 1
  • ARB options if ACE inhibitor not tolerated:
    • Candesartan: 4-8 mg once daily → 32 mg once daily 1

2. Beta-Blockers

• Start at low dose and titrate every 2 weeks if tolerated 1
• Evidence-based options only:
  • 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 once daily → 200 mg once daily 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Add when LVEF ≤35% or symptoms persist (NYHA II-IV) 3
• Options:
  • Spironolactone: 12.5-25 mg once daily → 25-50 mg once daily
  • Eplerenone: 25 mg once daily → 50 mg once daily 1
• Monitor potassium and renal function regularly

4. SGLT2 Inhibitors

• Add for all patients with HFrEF with eGFR >20 ml/min/1.73 m² 4, 1
• Options:
  • Dapagliflozin: 10 mg once daily
  • Empagliflozin: 10 mg once daily 1

Diuretics for Symptom Management

• Add diuretics for patients with fluid retention to improve symptoms 4
• Loop diuretics preferred over thiazides for symptom control 3
• Options:
  • Furosemide: 20-40 mg once or twice daily → up to 600 mg daily
  • Bumetanide: 0.5-1.0 mg once or twice daily → up to 10 mg daily
  • Torsemide: 10-20 mg once daily → up to 200 mg daily 4

Implementation Strategy

1. Initiation Phase:

   • Start with low doses of all medications
   • For patients with low blood pressure (SBP <100 mmHg), prioritize beta-blockers first, then add other agents 4
   • For patients with normal blood pressure, all four drug classes can be started simultaneously at low doses

2. Titration Phase:

   • Uptitrate each medication every 2 weeks as tolerated
   • Target maximum tolerated doses of each medication class
   • Monitor blood pressure, heart rate, renal function, and electrolytes at each titration step

3. Special Considerations:

   • If heart rate remains >70 bpm despite maximum beta-blocker, consider adding ivabradine 1
   • For patients with low blood pressure, consider reducing RAS inhibitor dose before discontinuing 4
   • For patients with eGFR <30 ml/min, carefully monitor renal function with diuretics and RAS inhibitors

Device Therapy Considerations

• Evaluate for ICD in patients with LVEF ≤30% who are at least 40 days post-MI and on optimal medical therapy 4
• Consider CRT for patients with LVEF ≤35%, QRS ≥150 ms, and left bundle branch block morphology 1, 5

Common Pitfalls to Avoid

1. Underutilization of evidence-based therapies:

   • Don't use non-evidence-based beta-blockers instead of proven ones (bisoprolol, carvedilol, metoprolol succinate) 1
   • Don't prematurely switch from ACE inhibitors to ARBs without trying to manage side effects 1

2. Harmful medications:

   • Avoid nondihydropyridine calcium channel blockers (verapamil, diltiazem) in HFrEF as they can worsen outcomes 4, 1
   • Avoid NSAIDs, COX-2 inhibitors, and Class I anti-arrhythmic agents 1

3. Inadequate dosing:

   • Don't settle for suboptimal doses; aim for target doses or maximum tolerated doses 3
   • Don't discontinue medications due to mild, asymptomatic low blood pressure 4

4. Poor monitoring:

   • Monitor daily weight with action plan for weight gain >2 kg in 3 days 1
   • Regular monitoring of renal function and electrolytes, especially with diuretics, ACE inhibitors, or ARBs 1

The comprehensive approach with quadruple therapy has been shown to provide substantial benefits, with estimates suggesting 2.7-8.3 additional years free from cardiovascular death or hospitalization compared to conventional therapy 6.