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

Initial Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

The initial management of HFrEF should include simultaneous initiation of four core medication classes: ARNI (sacubitril/valsartan) or ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, with in-hospital initiation strongly recommended to improve long-term adherence and outcomes. 1

Core Medication Classes and Dosing

First-Line Therapy

1. ARNI (Preferred) or ACE inhibitor/ARB

   • Sacubitril/valsartan (ARNI): Start with 49/51 mg BID, target 97/103 mg BID 1, 2
   • Enalapril (if ARNI not available): Start with 2.5 mg BID, target 10-20 mg BID 1, 3
   • Note: Allow 36-hour washout when switching from ACE inhibitor to ARNI 2

2. Beta-Blockers

   • Carvedilol: Start with 3.125 mg BID, target 25 mg BID (<85 kg) or 50 mg BID (≥85 kg) 1
   • Metoprolol succinate: Start with 12.5-25 mg daily, target 200 mg daily 1
   • Bisoprolol: Start with 1.25 mg daily, target 10 mg daily 1

3. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone: Start with 12.5-25 mg daily, target 25-50 mg daily 1
   • Eplerenone: Start with 25 mg daily, target 50 mg daily 1

4. SGLT2 Inhibitors

   • Dapagliflozin: 10 mg daily (no titration needed) 1
   • Empagliflozin: 10 mg daily (no titration needed) 1

Implementation Strategy

Modern Approach to Medication Initiation

• Simultaneous initiation of all four core medication classes is recommended rather than sequential addition 1
• In-hospital initiation is strongly recommended, associated with 34% reduction in mortality or HF hospitalization 1
• SGLT2 inhibitors are ideal for early initiation as they don't affect blood pressure or heart rate and require no dose adjustment 1

Monitoring and Dose Adjustment

• Monitor vital signs, volume status, renal function, and electrolytes during initiation phase 1
• Adjust doses based on:
  • Systolic blood pressure
  • Heart rate
  • Renal function
  • Potassium levels

Volume Management

• Loop diuretics should be used for volume overload at the lowest effective dose to maintain euvolemia 1
• Titrate diuretics based on clinical assessment of volume status

Common Challenges and Solutions

Clinical Inertia

• Problem: Delaying initiation of medications due to concerns about starting in hospitalized patients
• Solution: Evidence shows in-hospital initiation is safe and improves long-term adherence 1

Underdosing

• Problem: Only 17-29% of patients receive target doses of medications
• Solution: Implement structured titration protocols and utilize HF clinics 1

Incomplete GDMT

• Problem: Underutilization of MRAs
• Solution: Use SGLT2 inhibitors which may facilitate MRA use by reducing hyperkalemia risk 1

Device Therapy Considerations

For patients who remain symptomatic despite optimal medical therapy:

• ICD: Consider for primary prevention in patients with LVEF ≤30-35% and NYHA class II-III symptoms 1
• CRT: Consider for patients with LVEF ≤35%, NYHA class II-IV symptoms, and QRS duration ≥130 msec 1

Follow-up

• Regular follow-up every 1-2 weeks initially 1
• Assess vital signs, volume status, renal function, and electrolytes
• Adjust medications based on clinical status and laboratory results

Special Considerations

• Pregnancy: Discontinue ARNI/ACE inhibitors/ARBs when pregnancy is detected due to fetal toxicity 2
• Pediatric patients: Sacubitril/valsartan is indicated for symptomatic heart failure with systemic left ventricular systolic dysfunction in patients aged one year and older 2

The comprehensive implementation of this guideline-directed medical therapy approach can significantly reduce mortality and hospitalization rates, with evidence showing a 19.2% relative improvement in composite care measures over 24 months 1.