What are the initial and secondary treatment options for congestive heart failure (CHF) with reduced ejection fraction (HFrEF)?

Treatment of Heart Failure with Reduced Ejection Fraction (HFrEF)

The cornerstone of HFrEF treatment is quadruple therapy consisting of SGLT2 inhibitors, mineralocorticoid receptor antagonists (MRAs), beta-blockers, and either an angiotensin receptor-neprilysin inhibitor (ARNI) or ACE inhibitor/ARB, which should be initiated promptly to reduce mortality and hospitalizations. 1, 2

Initial Treatment Algorithm

Step 1: Foundational Medications (can be started simultaneously)

1. SGLT2 inhibitors

   • Dapagliflozin 10 mg daily or Empagliflozin 10 mg daily
   • Minimal effect on blood pressure, can be started early 1, 2
   • Monitor renal function and electrolytes

2. Mineralocorticoid Receptor Antagonists (MRAs)

   • Spironolactone 12.5-25 mg daily (target 25-50 mg daily) or
   • Eplerenone 25 mg daily (target 50 mg daily)
   • Monitor potassium and renal function 2

3. Beta-blockers

   • Carvedilol 3.125 mg twice daily (target 25 mg twice daily for weight <85 kg or 50 mg twice daily for weight ≥85 kg)
   • Metoprolol succinate 12.5-25 mg daily (target 200 mg daily)
   • Bisoprolol 1.25 mg once daily (target 10 mg once daily)
   • Titrate every 2 weeks as tolerated 2
   • Consider selective β₁ blockers if blood pressure is low 1

4. ARNI/ACEi/ARB

   • First choice: ARNI (Sacubitril/Valsartan)

     • Start at 24/26 mg twice daily (low dose) or 49/51 mg twice daily
     • Target dose: 97/103 mg twice daily 2, 3
     • Superior to ACEi for reducing morbidity and mortality 1

   • Alternative if ARNI not feasible: ACE inhibitor

     • Lisinopril 2.5-5 mg daily (target 20-40 mg daily)
     • Enalapril 2.5 mg twice daily (target 10-20 mg twice daily) 2, 4

   • If ACEi intolerant: ARB

     • Candesartan 4-8 mg daily (target 32 mg daily)
     • Valsartan 40 mg twice daily (target 160 mg twice daily) 2

Step 2: Additional Therapies Based on Clinical Characteristics

1. For patients in sinus rhythm with HR ≥70 bpm despite beta-blockers:

   • Add Ivabradine 1, 2
   • Can be used alone or with low-dose beta-blockers if beta-blockers not well tolerated

2. For self-identified African American patients:

   • Consider hydralazine and isosorbide dinitrate combination 1
   • Particularly beneficial when added to standard therapy

3. For patients with persistent volume overload:

   • Adjust diuretic therapy as needed
   • Monitor electrolytes and renal function

Medication Titration Strategy

1. Start at low doses and titrate gradually

   • Increase one medication at a time every 1-2 weeks 1, 2
   • Use small increments until reaching target dose or highest tolerated dose
   • Monitor blood pressure, heart rate, renal function, and electrolytes

2. For patients with low blood pressure (SBP <90 mmHg):

   • Start with SGLT2i and MRA as they have minimal effect on BP 1
   • Add low-dose beta-blocker if HR >70 bpm
   • Consider very low dose of ARNI (24/26 mg twice daily) or ACEi/ARB
   • Titrate slowly with small increments 1

Monitoring and Follow-up

1. Laboratory monitoring:

   • Check renal function and electrolytes 1-2 weeks after initiation or dose increase of ACEi/ARB/ARNI or MRA 2
   • Monitor potassium closely with MRAs
   • Check blood glucose with SGLT2i, especially in diabetic patients

2. Clinical monitoring:

   • Blood pressure and heart rate at each visit
   • Assess for symptoms of hypotension, worsening HF, or hyperkalemia
   • Daily weight monitoring (increase diuretic if weight increases by 1.5-2.0 kg over 2 days) 2

Common Pitfalls and Caveats

1. Underutilization of guideline-directed therapy

   • Only 1% of eligible patients receive target doses of all recommended medications 5
   • Don't stop at suboptimal doses without attempting titration

2. Excessive concern about low blood pressure

   • Asymptomatic low BP should not prevent initiation or uptitration of therapy 1
   • Focus on symptoms rather than absolute BP numbers

3. Inappropriate discontinuation during hospitalization

   • Continue HF medications during hospitalization when possible
   • Temporary dose reduction is preferable to discontinuation

4. Failure to switch from ACEi/ARB to ARNI

   • ARNI is superior to ACEi for reducing morbidity and mortality 1, 3
   • Consider switching stable patients from ACEi/ARB to ARNI

5. Neglecting SGLT2 inhibitors

   • These are now considered first-line therapy regardless of diabetes status 2, 6
   • Can be initiated early due to minimal effect on blood pressure

6. Inadequate diuretic adjustment

   • Adjust diuretics based on congestion status
   • Overdiuresis can limit uptitration of mortality-reducing therapies

By following this comprehensive approach to HFrEF management with prompt initiation of all four medication classes and systematic uptitration, mortality and hospitalization rates can be significantly reduced while improving quality of life for patients with heart failure.