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 quadruple therapy with SGLT2 inhibitors, beta-blockers, renin-angiotensin system inhibitors (preferably ARNI), and mineralocorticoid receptor antagonists, along with diuretics for symptom control. 1

First-Line Pharmacological Therapy

Core Medications for HFrEF

1. Diuretics - For patients with fluid retention to improve symptoms

   • Loop diuretics preferred over thiazides
   • Options: Furosemide 20-40 mg once/twice daily, Bumetanide 0.5-1.0 mg once/twice daily, or Torsemide 10-20 mg once daily 1

2. Renin-Angiotensin System Inhibitors

   • First choice: Sacubitril/Valsartan (ARNI) 1
     • Starting dose: 49/51 mg twice daily
     • Target dose: 97/103 mg twice daily 2
   • Alternative if ARNI not available/tolerated: ACE inhibitors
     • Lisinopril (2.5-5 mg → 20-40 mg daily)
     • Enalapril (2.5 mg → 10-20 mg twice daily)
     • Ramipril (1.25-2.5 mg → 10 mg daily) 1

3. Beta-Blockers

   • Carvedilol (3.125 mg → 25-50 mg twice daily)
   • Metoprolol succinate (12.5-25 mg → 200 mg daily)
   • Bisoprolol (1.25 mg → 10 mg daily) 1

4. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone (12.5-25 mg → 25-50 mg daily)
   • Eplerenone (25 mg → 50 mg daily) 1

5. SGLT2 Inhibitors

   • Dapagliflozin 10 mg daily or
   • Empagliflozin 10 mg daily 1

Initiation and Titration Strategy

Sequencing Approach

1. For patients with normal blood pressure (SBP >100 mmHg):

   • Start all medications at low doses simultaneously or in rapid sequence
   • Titrate each medication every 2 weeks to target doses 1

2. For patients with low blood pressure (SBP <100 mmHg):

   • Start with beta-blocker first
   • Add other agents sequentially as tolerated 1
   • Consider starting at half the recommended starting dose for:
     • Patients not currently taking ACE inhibitors/ARBs
     • Patients with severe renal impairment
     • Patients with moderate hepatic impairment 2

Monitoring During Titration

• Blood pressure and heart rate at each visit
• Renal function and electrolytes within 1-2 weeks after initiation or dose change
• Daily weight monitoring with action plan for weight gain >2 kg in 3 days 1

Device Therapy Evaluation

• ICD Evaluation: For patients with LVEF ≤30% who are at least 40 days post-MI and on optimal medical therapy 1
• CRT Consideration: For patients with LVEF ≤35%, QRS duration ≥150 ms, and left bundle branch block morphology 1

Medications to Avoid in HFrEF

• Nondihydropyridine calcium channel blockers (verapamil, diltiazem)
• NSAIDs and COX-2 inhibitors
• Class I anti-arrhythmic agents
• Thiazolidinediones
• Most antiarrhythmic drugs 1

Lifestyle Modifications

• Moderate sodium restriction (2-3 g/day)
• Fluid restriction of 1.5-2 L/day in advanced heart failure
• Regular physical activity with structured aerobic exercise program
• Smoking cessation
• Limited alcohol consumption 1

Expected Benefits of Comprehensive Therapy

Quadruple therapy with SGLT2 inhibitors, beta-blockers, ARNI, and MRAs can reduce:

• Risk of cardiovascular death or heart failure hospitalization by 62% (HR 0.38)
• All-cause mortality by 47% (HR 0.53) 3

Common Pitfalls and Caveats

1. Underdosing: Many patients remain on suboptimal doses. Always aim for target doses shown to be effective in clinical trials 4

2. Renal function concerns: Don't withhold therapy due to mild-moderate renal dysfunction. Close monitoring is required, but benefits often outweigh risks 1

3. Hypotension management: For symptomatic hypotension, consider reducing diuretic dose before reducing disease-modifying medications 1

4. Hyperkalemia risk: Monitor potassium levels closely when using MRAs, especially in combination with ACEi/ARB/ARNI 1

5. Delayed addition of therapies: All four medication classes should be initiated promptly rather than waiting for clinical deterioration 3

6. Failure to reassess: Regular reassessment of volume status, symptoms, and medication tolerance is essential 1

By implementing this comprehensive approach to HFrEF management, clinicians can significantly improve morbidity, mortality, and quality of life for patients with this condition.