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

Initial Management of Heart Failure with Reduced Ejection Fraction

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

Pharmacological Management Algorithm

First-Line Medications

1. SGLT2 inhibitors (Dapagliflozin 10mg daily or Empagliflozin 10mg daily)

   • Start early as they have minimal impact on blood pressure
   • Can be used in patients with eGFR >20 ml/min/1.73m² 2
   • Provide mortality benefit regardless of diabetes status 1

2. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone (start 12.5-25mg once daily, target 25-50mg once daily) or
   • Eplerenone (start 25mg once daily, target 50mg once daily)
   • Minimal impact on blood pressure 2
   • Monitor potassium and renal function

3. Beta-blockers

   • Start if heart rate >70 bpm
   • Options include:
     • Metoprolol succinate (start 12.5-25mg once daily, target 200mg once daily)
     • Bisoprolol (start 1.25mg once daily, target 10mg once daily)
     • Carvedilol (start 3.125mg twice daily, target 25-50mg twice daily)
   • Consider selective β₁ receptor blockers (metoprolol, bisoprolol) in patients with low blood pressure 2

4. Renin-Angiotensin System Inhibitors

   • Preferred: Sacubitril/valsartan (ARNI)
     • Start at 49/51mg twice daily (or 24/26mg twice daily if BP concerns)
     • Target dose: 97/103mg twice daily 3
   • Alternative (if ARNI not tolerated):
     • ACE inhibitors: Lisinopril (start 2.5-5mg daily, target 20-40mg daily), Enalapril (start 2.5mg twice daily, target 10-20mg twice daily) 4
     • ARBs (if ACE inhibitors not tolerated): Candesartan (start 4-8mg daily, target 32mg daily)

Titration Strategy

• Up-titrate one drug at a time using small increments every 2-4 weeks 2, 1
• For patients with low blood pressure:
  • Space out medications to reduce synergistic hypotensive effects
  • Consider physical training to improve orthostatic hypotension
  • Use compression stockings for orthostatic changes 2

Special Considerations

For Patients with Low Blood Pressure

1. Confirm low BP and assess symptoms
2. Consider stopping non-HF antihypertensives
3. Sequence of medications for low BP patients:
   • Start SGLT2i and MRA first (minimal BP impact)
   • Add beta-blocker if HR >70 bpm
   • Add low-dose ARNI/ACEi/ARB and titrate slowly 2

For Patients with Specific Conditions

• eGFR <30ml/min and HR <60 bpm:

  • Add SGLT2i if eGFR >20 ml/min
  • Consider ACEi/ARB/ARNI at low dose 2

• eGFR <30ml/min and HR >60 bpm:

  • Titrate beta-blocker if HR >50 bpm
  • Consider ACEi/ARB/ARNI at low dose 2

• eGFR >30ml/min and HR <60 bpm:

  • Reinitiate or up-titrate beta-blocker
  • Up-titrate ACEi/ARB/ARNI 2

• eGFR >30ml/min and HR >60 bpm:

  • Optimize MRA
  • Up-titrate beta-blocker if HR >50 bpm 2

Symptomatic Management

• Diuretics (e.g., furosemide) for patients with fluid retention

  • Adjust according to volume status
  • Be cautious as overdiuresis may lower BP 2

• Ivabradine for patients in sinus rhythm who cannot tolerate beta-blockers or have HR >70 bpm despite maximum tolerated beta-blocker dose 2, 1

• Digoxin for rate control in patients with atrial fibrillation who cannot tolerate beta-blockers 2

Monitoring and Follow-up

• Close follow-up every 2-4 weeks during medication initiation and titration
• Monitor:
  • Blood pressure and heart rate
  • Renal function and electrolytes (particularly potassium)
  • Symptoms and signs of heart failure
  • Daily weight (action plan for >2kg gain in 3 days) 1

Common Pitfalls to Avoid

1. Premature discontinuation of therapy due to asymptomatic changes in vital signs or lab values

   • Discontinuation of ARNI/ACEi/ARB is associated with almost twofold increased risk of mortality 5
   • Shifting from sacubitril-valsartan to ACEi/ARB leads to deterioration of LVEF and worsening functional class 6

2. Inappropriate medication combinations:

   • Avoid combining ARB with ACEi and MRA (increased risk of renal dysfunction and hyperkalemia) 1
   • Avoid NSAIDs, COX-2 inhibitors, and thiazolidinediones in heart failure patients 1
   • Avoid diltiazem/verapamil in HFrEF patients 1

3. Inadequate titration of medications to target doses

   • Use forced-titration strategy to progressively increase doses 1
   • Aim for maximum tolerated dose of each agent

4. Overlooking non-pharmacological interventions:

   • Regular physical activity (structured aerobic exercise program)
   • Moderate sodium restriction
   • Smoking cessation
   • Limited alcohol consumption 1

By following this comprehensive approach to HFrEF management, focusing on early initiation and optimization of quadruple therapy, patients can experience significant reductions in mortality and hospitalizations while improving quality of life.