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

First-Line Medications for HFrEF

Renin-Angiotensin System Inhibition

• First choice: Sacubitril/valsartan (ARNI)

  • Preferred over ACE inhibitors for NYHA class II-III HFrEF patients 1
  • Starting dose: 49/51 mg twice daily
  • Target dose: 97/103 mg twice daily 1, 2
  • Contraindicated with concomitant ACE inhibitor use (require 36-hour washout period) 2
  • Reduces risk of cardiovascular death and hospitalization 2

• Alternative if ARNI not tolerated: ACE inhibitors

  • Options include Lisinopril (2.5-5 mg daily → 20-40 mg daily), Enalapril (2.5 mg twice daily → 10-20 mg twice daily), or Ramipril (1.25-2.5 mg daily → 10 mg daily) 1
  • Provide modest mortality benefit (5-16% risk reduction) compared to ARNI 3

• Alternative if ACE inhibitors not tolerated: ARBs

  • Example: Candesartan (4-8 mg daily → 32 mg daily) 1

Beta-Blockers

• Evidence-based options that prolong life: 3, 1
  • Carvedilol (3.125 mg twice daily → 25-50 mg twice daily)
  • Metoprolol succinate (12.5-25 mg daily → 200 mg daily)
  • Bisoprolol (1.25 mg daily → 10 mg daily)
• Provide at least 20% reduction in mortality risk 3
• Specifically reduce risk of sudden death 3

Mineralocorticoid Receptor Antagonists (MRAs)

• Options: 1, 4
  • Spironolactone (12.5-25 mg daily → 25-50 mg daily)
  • Eplerenone (25 mg daily → 50 mg daily)
• Indicated for NYHA Class III-IV heart failure with reduced ejection fraction 4
• Provide at least 20% reduction in mortality risk 3
• Reduce risk of sudden death 3

SGLT2 Inhibitors

• Options: 1
  • Dapagliflozin (10 mg daily)
  • Empagliflozin (10 mg daily)
• Provide mortality benefit regardless of diabetes status 1

Implementation Strategy

1. Initiation Phase:

   • Start with low doses of each medication class
   • Begin multiple agents simultaneously or in rapid sequence (within 1-2 weeks)
   • Monitor blood pressure, heart rate, renal function, and electrolytes closely

2. Titration Phase:

   • Follow a forced-titration strategy as used in landmark trials 3
   • Increase doses progressively at 2-4 week intervals 1, 2
   • Target achieving the maximum tolerated dose of each agent

3. Maintenance Phase:

   • Continue efforts to reach target doses even if initial attempts are unsuccessful
   • Temporary dose reductions may be needed, but attempt to re-titrate when possible

Clinical Considerations and Pitfalls

Common Pitfalls to Avoid

• Underdosing: Most patients in clinical practice receive starting doses indefinitely, which may not provide optimal mortality benefit 3, 5
• Incomplete therapy: Failing to prescribe all four medication classes when indicated 1
• Premature discontinuation: Asymptomatic changes in vital signs or lab values should not automatically prevent uptitration 3

Important Monitoring Parameters

• Renal function: ACE inhibitors, ARBs, and sacubitril/valsartan can impair renal function 1, 6
• Potassium levels: MRAs and ACE inhibitors/ARBs increase risk of hyperkalemia 1
• Blood pressure: Most agents (except SGLT2 inhibitors) significantly reduce blood pressure 6
• Volume status: Daily weight monitoring with action plan for weight gain >2 kg in 3 days 1

Contraindications and Precautions

• Avoid NSAIDs and COX-2 inhibitors in all heart failure patients 1
• Avoid combining ARB with ACE inhibitor and MRA due to increased risk of renal dysfunction 1
• Avoid diltiazem/verapamil in HFrEF patients 1
• Discontinue sacubitril/valsartan when pregnancy is detected 2

Special Situations

Hyperkalemia Management

• If K+ >5.5 mEq/L: Reduce or temporarily discontinue RAAS inhibitors
• Consider patiromer for persistent hyperkalemia in patients who would benefit from RAAS inhibitors 1

Device Therapy Considerations

• Evaluate for cardiac resynchronization therapy if QRS duration ≥150 msec with LBBB morphology 1
• Consider ICD for patients with LVEF ≤35% despite ≥3 months of optimal medical therapy 1

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