What is the treatment approach for patients with low Ejection Fraction (EF)?

Treatment for Low Ejection Fraction (EF)

Patients with reduced ejection fraction should receive a four-drug regimen consisting of an ACE inhibitor (or ARB/ARNI), beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor to reduce mortality and hospitalizations. 1

First-Line Pharmacological Therapy

Step 1: Foundation Therapy

1. ACE inhibitor (or alternative):

   • Start ACE inhibitor as soon as possible, blood pressure and renal function permitting 1
   • If ACE inhibitor not tolerated (due to cough or angioedema), use an ARB 1
   • Sacubitril/valsartan (ARNI) is recommended as a replacement for ACE inhibitors in patients who remain symptomatic despite optimal treatment 1
   • Dosing: Start low and titrate up (e.g., lisinopril starting at 2.5-5mg, target 20-35mg daily) 2

2. Beta-blocker:

   • Start as soon as possible after stabilization, blood pressure and heart rate permitting 1
   • Continue during episodes of decompensation when possible 1
   • Evidence-based options include carvedilol, metoprolol succinate, or bisoprolol

3. Mineralocorticoid receptor antagonist (MRA):

   • Add for patients who remain symptomatic despite ACE inhibitor and beta-blocker 1
   • Can be started even in relatively hypotensive patients as it has minimal effect on blood pressure 1
   • Monitor renal function and potassium levels closely

4. SGLT2 inhibitor:

   • Now considered a Class I, Level A recommendation for HFrEF 1
   • Provides substantial risk reduction across multiple endpoints
   • Well-tolerated with minimal impact on blood pressure

Additional Therapies Based on Clinical Scenario

1. Diuretics:

   • Recommended for symptom relief and to improve exercise capacity in patients with signs of congestion 1
   • Not shown to reduce mortality but essential for managing volume status

2. Digoxin:

   • Consider for controlling ventricular rate in atrial fibrillation 1
   • May provide symptom benefit and reduce hospitalization risk in severe systolic HF 1

3. Device Therapy:

   • ICD: Recommended for patients with symptomatic HF (NYHA II-III), LVEF ≤35% despite ≥3 months of optimal medical therapy 1
   • CRT: Consider for patients with LVEF ≤35%, NYHA class III-IV symptoms, and QRS duration >120ms 3

Medication Titration Algorithm

1. Initiation Phase:

   • Begin medications at low doses
   • Can start medications simultaneously or sequentially based on clinical factors 1
   • Monitor blood pressure, heart rate, renal function, and electrolytes

2. Titration Phase:

   • Gradually increase doses toward target doses used in clinical trials
   • Titrate up as far as possible before discharge if hospitalized 1
   • Make a plan to complete dose up-titration after discharge

3. Maintenance Phase:

   • Continue to monitor for side effects and adjust as needed
   • If hypotension occurs (SBP <90 mmHg):
     • First reduce/eliminate non-HF medications that lower blood pressure
     • Reduce diuretic dose if no signs of congestion
     • Consult HF specialist before reducing doses of mortality-reducing medications 4

Special Considerations

• Asymptomatic LV dysfunction: ACE inhibitors and beta-blockers are still recommended to prevent progression to symptomatic HF 1, 5
• Post-MI patients: Start ACE inhibitor and beta-blocker therapy within days after the ischemic event 1
• Avoid: Calcium channel blockers (especially diltiazem and verapamil), NSAIDs, and most antiarrhythmic drugs in HFrEF patients 1, 3

Monitoring and Follow-up

• Regular assessment of:
  • Symptoms and functional capacity
  • Volume status
  • Blood pressure and heart rate
  • Renal function and electrolytes (especially with ACE inhibitors and MRAs)
  • Medication adherence and side effects

Common Pitfalls to Avoid

1. Undertreatment: Failing to titrate medications to target doses shown to be effective in clinical trials
2. Premature discontinuation: Stopping guideline-directed therapy due to mild, asymptomatic hypotension
3. Inadequate monitoring: Not checking renal function and electrolytes after initiation or dose increases
4. Delaying therapy: Waiting too long to start foundational therapies in eligible patients
5. Overdiuresis: Excessive diuresis leading to hypotension and renal dysfunction that limits use of mortality-reducing medications

By following this comprehensive approach to managing patients with low ejection fraction, you can significantly improve outcomes including mortality, hospitalization rates, and quality of life.