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

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

The initial management for patients with HFrEF should focus on quadruple therapy with SGLT2 inhibitors, beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists to significantly reduce mortality and hospitalizations. 1

Foundational Medications for HFrEF

First-Line Medications

1. SGLT2 Inhibitors

   • Dapagliflozin (10 mg once daily) or Empagliflozin (10 mg once daily)
   • Provide early mortality and hospitalization benefits 2
   • Minimal effect on blood pressure, making them suitable for early initiation 3

2. Beta-Blockers

   • Options: Carvedilol (3.125 mg twice daily), Bisoprolol (1.25 mg once daily), or Metoprolol succinate (12.5-25 mg once daily)
   • Start at low doses and titrate gradually every 2 weeks 2
   • For patients with low blood pressure, selective β₁ receptor blockers (bisoprolol, metoprolol) may be preferred over non-selective beta-blockers with vasodilatory properties 3

3. Renin-Angiotensin System Inhibitors

   • First choice: Sacubitril/Valsartan (ARNI) starting at 49/51 mg twice daily
   • Alternatives: ACE inhibitors (Lisinopril, Enalapril, Ramipril) or ARBs if ARNI not tolerated 2
   • For patients with low blood pressure, start with very low dose (e.g., sacubitril/valsartan 25 mg twice daily) 3

4. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone (12.5-25 mg once daily) or Eplerenone (25 mg once daily)
   • Monitor potassium and renal function closely 2
   • Avoid if eGFR <30 mL/min/1.73m² or K+ >5.0 mEq/L 2

Diuretics for Symptom Relief

• Loop diuretics (Furosemide, Torsemide, Bumetanide) for congestion management
• Titrate to achieve euvolemia and relieve symptoms 2
• For hospitalized patients, initial IV dose should equal or exceed chronic oral daily dose 3

Rapid Sequencing Strategy

Recent evidence supports an accelerated approach to initiating all four foundational medications within 2-4 weeks rather than the conventional approach that takes ≥6 months 4:

1. Week 1: Simultaneously initiate beta-blocker and SGLT2 inhibitor
2. Week 2-3: Add sacubitril/valsartan (or ACE inhibitor/ARB)
3. Week 3-4: Add mineralocorticoid receptor antagonist

This sequencing can be adjusted based on patient circumstances, particularly for those with low blood pressure 3, 4.

Special Considerations for Low Blood Pressure

For patients with low blood pressure (common in HFrEF):

• Start with SGLT2 inhibitors and MRAs as they have minimal effect on blood pressure 3
• Use selective β₁ receptor blockers (bisoprolol, metoprolol) rather than non-selective beta-blockers 3
• Consider very low starting doses of ACE inhibitors/ARNIs and gradual up-titration 3
• If beta-blockers are not hemodynamically tolerated and patient is in sinus rhythm, consider ivabradine 3
• Space out medications to reduce synergistic hypotensive effects 3

Monitoring and Follow-up

• Monitor fluid intake/output, vital signs, body weight (daily at same time), and clinical signs/symptoms of congestion 3
• Check daily serum electrolytes, urea nitrogen, and creatinine during active medication titration 3
• Reconcile medications at every hospital admission and discharge 3
• Continue chronic HFrEF therapies during hospitalization unless hemodynamic instability or contraindications exist 3
• For hospitalized patients not previously on guideline-directed therapy, initiate these medications before discharge when stable 3

Comprehensive Discharge Planning

• Provide written discharge instructions covering diet, medications, activity level, follow-up appointments, daily weight monitoring, and when to seek medical attention 3
• Implement post-discharge care systems to facilitate transition to effective outpatient care 3

Common Pitfalls to Avoid

1. Underutilization of quadruple therapy - Despite strong evidence, guideline-directed medical therapy is vastly underutilized in clinical practice 1
2. Focusing on up-titration before establishing all four medication classes - Low starting doses of all four foundational drugs provide substantial benefits and should take precedence over up-titration to target doses 4
3. Discontinuing beneficial medications during hospitalization - Continue chronic HFrEF therapies during hospitalization unless hemodynamically unstable 3
4. Inadequate diuresis - When diuresis is inadequate, consider higher doses of loop diuretics, adding a second diuretic, or continuous infusion 3
5. Medications to avoid in HFrEF:
   • NSAIDs and COX-2 inhibitors
   • Thiazolidinediones (glitazones)
   • Diltiazem/verapamil 2

By implementing this comprehensive approach to HFrEF management with a focus on early initiation of all four foundational medication classes, patients can achieve significant reductions in mortality and hospitalizations while improving quality of life.