What beta-blocker (beta-adrenergic blocker) to choose for Heart Failure with Reduced Ejection Fraction (HFrEF)?

Beta Blocker Selection in Heart Failure with Reduced Ejection Fraction (HFrEF)

In patients with HFrEF, only three specific beta blockers - bisoprolol, carvedilol, or sustained-release metoprolol succinate - should be used as they are the only ones proven to reduce mortality and hospitalizations. 1

Evidence-Based Beta Blocker Options

The 2022 AHA/ACC/HFSA guidelines provide a Class I, Level A recommendation for using only these three beta blockers in HFrEF:

• Bisoprolol
• Carvedilol
• Metoprolol succinate (extended-release)

Dosing Protocol

Beta-Blocker	Starting Dose	Target Dose	Titration Schedule
Metoprolol Succinate	12.5-25 mg once daily	200 mg once daily	Every 2 weeks
Carvedilol	3.125 mg twice daily	25-50 mg twice daily	Double dose every 2 weeks
Bisoprolol	1.25 mg once daily	10 mg once daily	Double dose every 2 weeks

Clinical Considerations for Selection

Cardioselectivity

• Bisoprolol and metoprolol succinate: More cardioselective (β1-selective)
• Carvedilol: Non-selective (blocks both β1 and β2 receptors) with additional α1-blocking properties

Special Patient Populations

1. Patients with bronchospastic airway disease:

   • Prefer cardioselective agents (bisoprolol or metoprolol succinate) 2
   • Monitor closely for bronchospasm

2. Patients with peripheral vascular disease:

   • Carvedilol may offer advantages due to α1-blocking vasodilatory effects

3. Diabetic patients:

   • Carvedilol may have more favorable effects on glycemic control and insulin sensitivity

4. Patients with hypotension concerns:

   • Consider bisoprolol or metoprolol succinate as they have less vasodilatory effect than carvedilol

Implementation Strategy

1. Initiation:

   • Start at low doses in stable patients
   • Do not initiate during acute decompensation requiring IV inotropes
   • Begin after optimization of volume status 1

2. Titration:

   • Follow "start low, go slow" approach
   • Aim for target doses or highest tolerated dose
   • Allow 2-week intervals between dose increases

3. Monitoring:

   • Heart rate (target >50 bpm)
   • Blood pressure (avoid symptomatic hypotension)
   • Clinical status (symptoms, signs of congestion, weight)

Management of Common Challenges

• Worsening congestion: Double diuretic dose and/or halve beta blocker dose
• Fatigue: Consider reducing beta blocker dose by 50%
• Bradycardia (<50 bpm) with symptoms: Reduce beta blocker dose by 50%
• Hypotension: First reduce vasodilators, then consider beta blocker dose reduction

Important Cautions

• Do not abruptly discontinue beta blockers due to risk of rebound ischemia and arrhythmias
• These benefits are not a class effect - other beta blockers have not demonstrated mortality benefit in HFrEF 1
• Even if symptoms do not improve, maintain long-term treatment to reduce cardiovascular events

Integration with Other HFrEF Therapies

Beta blockers should be used as part of comprehensive GDMT for HFrEF, which includes:

• ACEi/ARB/ARNi
• Mineralocorticoid receptor antagonists
• SGLT2 inhibitors

Conclusion

While all three evidence-based beta blockers (bisoprolol, carvedilol, and metoprolol succinate) have demonstrated mortality benefit in HFrEF, the choice between them should be based on patient-specific factors such as comorbidities, hemodynamic status, and tolerability. The most important principle is to use one of these three proven agents and titrate to target doses as tolerated.