What is the initial treatment for patients with heart failure, particularly those with reduced ejection fraction?

Initial Treatment for Heart Failure with Reduced Ejection Fraction

For patients with heart failure with reduced ejection fraction (HFrEF), the initial treatment should include quadruple therapy with SGLT2 inhibitors, beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists to significantly reduce mortality and hospitalizations. 1

Core Medication Classes for HFrEF

First-Line Medications

1. SGLT2 Inhibitors

   • Preferred agents: Dapagliflozin (10 mg once daily) or Empagliflozin (10 mg once daily) 1
   • Provide early mortality and hospitalization benefits
   • Minimal effect on blood pressure, making them ideal initial agents 1
   • Can be used in patients with eGFR >20 ml/min/1.73 m² 2

2. Beta-Blockers

   • Evidence-based options: Carvedilol, Bisoprolol, or Metoprolol succinate 1
   • Starting doses:
     • Bisoprolol: 1.25 mg once daily (target: 10 mg once daily)
     • Carvedilol: 3.125 mg twice daily (target: 25-50 mg twice daily)
     • Metoprolol succinate: 12.5-25 mg once daily (target: 200 mg once daily) 1
   • Reduce mortality by at least 20% 2
   • Specifically shown to reduce sudden death 2

3. Renin-Angiotensin System Inhibitors

   • Options include:
     • ACE inhibitors (e.g., Lisinopril, Enalapril, Ramipril)
     • ARBs (e.g., Candesartan) if ACE inhibitors not tolerated
     • ARNI (Sacubitril/Valsartan) - preferred over ACE inhibitors when possible 1
   • Starting doses:
     • Sacubitril/Valsartan: 49/51 mg twice daily (target: 97/103 mg twice daily)
     • Lisinopril: 2.5-5 mg once daily (target: 20-40 mg once daily)
     • Enalapril: 2.5 mg twice daily (target: 10-20 mg twice daily) 1
   • ACE inhibitors/ARBs provide modest mortality benefit (5-16% risk reduction) 2

4. Mineralocorticoid Receptor Antagonists (MRAs)

   • Options: Spironolactone or Eplerenone 1
   • Starting doses:
     • Spironolactone: 12.5-25 mg once daily (target: 25-50 mg once daily)
     • Eplerenone: 25 mg once daily (target: 50 mg once daily) 1
   • Indicated for treatment of NYHA Class III-IV heart failure with reduced ejection fraction 3
   • Reduce mortality by at least 20% 2
   • Specifically shown to reduce sudden death 2

Medication Titration Strategy

1. Start Low, Go Slow

   • Begin with low doses and gradually up-titrate
   • Space out medications to reduce synergistic hypotensive effects 2
   • Up-titrate one drug at a time 2
   • Aim for target doses used in clinical trials 2

2. Titration Schedule

   • Increase doses in planned increments at specific time intervals
   • For beta-blockers, titrate gradually every 2 weeks 1
   • Continue titration until target dose is achieved or patient experiences adverse events 2

3. Blood Pressure Considerations

   • If low blood pressure is a concern, start with SGLT2 inhibitors and MRAs as they have minimal effect on blood pressure 1
   • Consider selective β₁ receptor blockers rather than non-selective beta-blockers 1
   • Use very low starting doses of ACE inhibitors/ARNIs with gradual up-titration 1

Adjunctive Therapies

1. Loop Diuretics

   • Used for symptom relief and congestion management
   • Titrate to achieve euvolemia and relieve symptoms 1
   • Not shown to reduce mortality but essential for symptom management

2. Ivabradine

   • Consider for patients in sinus rhythm with heart rate ≥70 bpm despite maximally tolerated beta-blocker therapy 4
   • Reduces hospitalization for worsening heart failure 4

3. Hydralazine and Isosorbide Dinitrate

   • Consider particularly for self-described African American patients with class II-IV HF 5
   • Can prolong survival but may be inferior to ACE inhibitors for mortality reduction 2

Common Pitfalls and Caveats

1. Underdosing

   • In clinical practice, most patients receive starting doses indefinitely rather than target doses 2
   • Subtarget dosing regimens may have benefits, but their ability to prolong life has not been established 2

2. Medication Interactions and Contraindications

   • Avoid NSAIDs and COX-2 inhibitors in all heart failure patients 1
   • Avoid thiazolidinediones (glitazones) in heart failure patients 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

3. Special Considerations

   • For patients with low blood pressure:
     • Space out medications to reduce hypotensive effects
     • Implement non-pharmacological interventions like exercise and compression stockings 2
   • For patients with renal dysfunction (eGFR <30 ml/min):
     • Consider reducing doses of RAS inhibitors and MRAs 2
   • For patients with bradycardia (HR <60 bpm):
     • Consider reducing beta-blockers or adding pacing 2

By following this comprehensive approach to HFrEF treatment, clinicians can significantly improve outcomes, including mortality reduction and decreased hospitalizations for heart failure patients.