What medications are recommended for a patient with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AFib)?

Medication Management for Heart Failure with Reduced Ejection Fraction and Atrial Fibrillation

For patients with heart failure with reduced ejection fraction (HFrEF) and atrial fibrillation (AFib), a comprehensive medication regimen should include four core medication classes: an ARNI (sacubitril/valsartan) or ACEi/ARB, a beta-blocker, a mineralocorticoid receptor antagonist (MRA), and an SGLT2 inhibitor, along with anticoagulation and rate control therapy. 1

Core HFrEF Medications

• ARNI (Angiotensin Receptor-Neprilysin Inhibitor): Sacubitril/valsartan is recommended as first-line therapy or as replacement for ACEi/ARB in patients with HFrEF to reduce mortality and hospitalization 1, 2

  • Starting dose: 49/51 mg twice daily for most patients; 24/26 mg twice daily for those with severe renal impairment, moderate hepatic impairment, or elderly patients (≥75 years) 2, 3
  • Target dose: 97/103 mg twice daily 2, 3

• Beta-blockers: Use one of the three beta-blockers proven to reduce mortality (bisoprolol, carvedilol, or metoprolol succinate) 1, 4

  • Metoprolol succinate: Starting dose 12.5-25 mg once daily, target dose 200 mg once daily 1, 4
  • Carvedilol: Starting dose 3.125 mg twice daily, target dose 25-50 mg twice daily 1
  • Bisoprolol: Starting dose 1.25 mg once daily, target dose 10 mg once daily 1

• Mineralocorticoid Receptor Antagonists (MRAs): Add spironolactone or eplerenone 1

  • Spironolactone: Starting dose 12.5-25 mg once daily, target dose 25-50 mg once daily 1
  • Eplerenone: Starting dose 25 mg once daily, target dose 50 mg once daily 1

• SGLT2 Inhibitors: Add dapagliflozin or empagliflozin to reduce hospitalization and death risk 1, 2

Specific Management for Atrial Fibrillation

• Anticoagulation: Required in most patients with HFrEF and AFib to prevent stroke 5

• Rate Control: Target heart rate 60-100 bpm at rest 1

  • Beta-blockers are first-line for rate control (already part of HFrEF therapy) 1, 5
  • Digoxin can be added for additional rate control, especially in patients with persistent symptoms despite beta-blockers 1, 6
    • Starting dose: 0.0625-0.25 mg daily 1
    • Monitor for toxicity with plasma concentrations exceeding 1.2 ng/mL 1

• Avoid: Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with HFrEF as they have negative inotropic effects 1

Diuretic Therapy

• Loop Diuretics: Use for symptom relief and fluid management 1
  • Furosemide: 20-40 mg once or twice daily, maximum 600 mg daily 1
  • Torsemide: 10-20 mg once daily, maximum 200 mg daily 1
  • Bumetanide: 0.5-1.0 mg once or twice daily, maximum 10 mg daily 1

Treatment Algorithm

1. Start with core HFrEF medications:

   • Begin ARNI (or ACEi/ARB if ARNI not feasible)
   • Add beta-blocker (metoprolol succinate, carvedilol, or bisoprolol)
   • Add MRA (spironolactone or eplerenone)
   • Add SGLT2 inhibitor 1

2. Add AFib-specific therapy:

   • Anticoagulation based on stroke risk
   • Optimize beta-blocker dose for rate control
   • Add digoxin if needed for additional rate control 1, 5, 6

3. Add diuretics as needed for symptom relief and fluid management 1

Important Considerations

• Patients with HFrEF and AFib have higher mortality and morbidity than those with HFrEF alone 5, 6
• Patients with AFib more often receive beta-blockers (81.7% vs. 79.7%), MRAs (57.1% vs. 51.7%), and diuretics (89.7% vs. 80.6%) compared to those without AFib 6
• AFib can both precipitate and be a consequence of HFrEF 5
• Catheter ablation for AFib in patients with HFrEF has shown superiority in improving survival, quality of life, and ventricular function compared to antiarrhythmic drugs and rate control therapies 5

Common Pitfalls to Avoid

• Failing to anticoagulate patients with HFrEF and AFib, increasing stroke risk 5
• Using non-dihydropyridine calcium channel blockers (diltiazem, verapamil) which can worsen heart failure 1
• Inadequate dosing of beta-blockers for rate control 4, 6
• Not distinguishing between metoprolol tartrate and succinate formulations (only succinate has evidence for HFrEF) 4
• Failing to uptitrate medications to target doses shown to improve outcomes in clinical trials 1, 4