Treatment for Heart Failure with Reduced Ejection Fraction (HFrEF)
The optimal treatment for HFrEF requires quadruple therapy with SGLT2 inhibitors, beta-blockers, renin-angiotensin system inhibitors (preferably ARNi), and mineralocorticoid receptor antagonists (MRAs) to significantly reduce mortality and hospitalizations. 1
First-Line Medications for HFrEF
SGLT2 Inhibitors
- Start with dapagliflozin 10 mg daily or empagliflozin 10 mg daily
- Can be initiated early regardless of diabetes status
- No dose titration required
Beta-Blockers
- Evidence-based options:
- Bisoprolol: Start 1.25 mg once daily, target 10 mg once daily
- Carvedilol: Start 3.125 mg twice daily, target 25-50 mg twice daily
- Metoprolol succinate: Start 12.5-25 mg once daily, target 200 mg once daily
- Monitor heart rate and blood pressure during titration
Renin-Angiotensin System Inhibitors
- Preferred option: Angiotensin Receptor-Neprilysin Inhibitor (ARNi)
- Sacubitril/valsartan: Start 49/51 mg twice daily, target 97/103 mg twice daily 2
- Requires 36-hour washout period if switching from ACE inhibitor
- Alternative if ARNi not tolerated:
- ACE inhibitors (e.g., lisinopril, enalapril, ramipril)
- ARBs if ACE inhibitors cause cough or angioedema (e.g., candesartan)
Mineralocorticoid Receptor Antagonists (MRAs)
- Spironolactone: Start 12.5-25 mg once daily, target 25-50 mg once daily
- Eplerenone: Start 25 mg once daily, target 50 mg once daily
- Monitor potassium and renal function
Treatment Algorithm
Initial Assessment:
- Confirm HFrEF diagnosis (LVEF ≤40%)
- Assess volume status and need for diuretics
- Evaluate renal function, electrolytes, and blood pressure
Initiation Strategy:
- For stable patients: Medications may be started simultaneously at low doses or sequentially
- For patients with low blood pressure: Start with SGLT2i and MRA, then add beta-blocker, followed by low-dose ARNi/ACEi/ARB
Titration Plan:
- Increase doses every 2-4 weeks as tolerated
- Target maximum tolerated doses of each medication class
- Monitor electrolytes and renal function 1-2 weeks after initiation and dose changes
Symptom Management:
- Use loop diuretics (e.g., furosemide) as needed for congestion
- Adjust diuretic dose based on symptoms and volume status
Additional Therapies
Device Therapy
- ICD for patients with LVEF ≤35% and NYHA Class II-III symptoms 3
- CRT for patients with LVEF ≤35%, QRS ≥150ms, and left bundle branch block morphology 3
Specific Situations
- Iron deficiency: Consider intravenous iron supplementation
- Persistent elevated heart rate (>70 bpm) despite beta-blocker: Consider ivabradine
- African American patients: Consider hydralazine/isosorbide dinitrate combination
Monitoring and Follow-up
- Regular assessment of:
- Symptoms and functional capacity
- Volume status
- Blood pressure and heart rate
- Electrolytes and renal function
- Medication adherence and side effects
Clinical Impact of Comprehensive Therapy
The combined use of all four medication classes (SGLT2i, beta-blocker, ARNi/ACEi/ARB, and MRA) can provide substantial benefits:
- Estimated 62% reduction in the risk of cardiovascular death or heart failure hospitalization 4
- Potential for 1.4-6.3 additional years of survival depending on age 4
Common Pitfalls to Avoid
- Underdosing medications: Always aim for target doses or maximum tolerated doses
- Premature discontinuation: Don't stop medications due to mild, transient side effects
- Inadequate monitoring: Regular follow-up of renal function and electrolytes is essential
- Failure to initiate all four medication classes: Each class provides additive benefits
- Overdiuresis: Excessive diuresis can lead to hypotension and renal dysfunction
- Delaying device therapy evaluation: Refer eligible patients for device therapy assessment
By following this comprehensive approach to HFrEF management, you can significantly improve patient outcomes, reduce hospitalizations, and extend survival.