What is the initial treatment for a patient with Heart Failure with Reduced Ejection Fraction (HFrEF)?

Initial Treatment for Heart Failure with Reduced Ejection Fraction (HFrEF)

The initial treatment for HFrEF should begin with ACE inhibitors as first-line therapy, followed by evidence-based beta-blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT2 inhibitors, with careful titration of each medication to target doses as tolerated. 1

First-Line Medications and Sequence

Step 1: ACE Inhibitors/ARNIs

• Start with an ACE inhibitor at a low dose and gradually titrate up to target doses 1
  • Example: Enalapril starting at 2.5mg twice daily, titrating to 10-20mg twice daily 2
• For patients who cannot tolerate ACE inhibitors, ARBs are an acceptable alternative 3
• Consider sacubitril/valsartan (ARNI) as an alternative to ACE inhibitors
  • Starting dose: 49/51mg twice daily
  • Target dose: 97/103mg twice daily 4
  • Note: Requires 36-hour washout period when switching from ACE inhibitor 4

Step 2: Beta-Blockers

• Add evidence-based beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) 1, 5
• Start at low doses and gradually titrate every 1-2 weeks as tolerated 1
• If heart rate >70 bpm and patient has low blood pressure, selective β₁ receptor blockers may be preferred due to lesser BP-lowering effects 3

Step 3: Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone or eplerenone, particularly for patients with NYHA class II-IV symptoms 1
• Monitor potassium and renal function closely

Step 4: SGLT2 Inhibitors

• Add dapagliflozin or empagliflozin to reduce mortality and hospitalization 1, 6
• These can be started early in treatment as they typically don't lower blood pressure significantly 3

Special Considerations

Patients with Low Blood Pressure

• For patients with low blood pressure, consider:
  1. Starting SGLT2i and MRA first as they do not significantly lower BP 3
  2. Then add low-dose beta-blocker if heart rate >70 bpm or low-dose ACE inhibitor/ARNI 3
  3. Titrate medications weekly with small increments until reaching target dose or highest tolerated dose 3
  4. If beta-blockers are not hemodynamically tolerated, ivabradine may be a viable alternative for patients in sinus rhythm 3

Diuretic Therapy

• Loop diuretics should be administered for patients with fluid retention 3, 1
• Adjust diuretic dose according to volume status to avoid overdiuresis which may result in lower BP 3
• Daily weight monitoring with instructions to increase diuretic dose if weight increases by 1.5-2.0 kg over 2 days 1

Titration Strategy

• Apply a "forced-titration strategy" similar to landmark clinical trials 3
• Initiate or up-titrate one drug at a time using small increments 3
• Monitor closely with follow-up every 1-2 weeks during titration 3, 1
• Aim for target doses or highest tolerated doses of each medication 7

Common Pitfalls and Caveats

1. Underutilization of GDMT: Despite strong evidence, GDMT is often underutilized in clinical practice 8, 5, 9

   • Only 63.8% of eligible patients receive evidence-based beta-blockers and even fewer (17.6%) receive MRAs 5
   • Less than 1% of patients achieve target doses of all recommended medications simultaneously 7

2. Medication Intolerance Management:

   • For patients who cannot tolerate ACE inhibitors, ARBs are an acceptable alternative 3
   • For patients who cannot tolerate beta-blockers and are in sinus rhythm, ivabradine may be used 3
   • For patients with low BP, start with medications that have minimal BP-lowering effects 3, 6

3. Monitoring Requirements:

   • Monitor renal function and electrolytes before initiation, 1-2 weeks after each dose increase, and every 3-6 months thereafter 1
   • Avoid excessive diuresis which can worsen renal function and fluid retention 1

4. Specialist Referral:

   • Patients seen in heart failure clinics are more likely to receive appropriate GDMT 5
   • Consider referral to a heart failure specialist for patients with difficulty tolerating medications or with complex comorbidities 5, 9

By following this structured approach to initiating and titrating GDMT for HFrEF, clinicians can optimize outcomes for patients while minimizing adverse effects.