Beta-Blockers Indicated for HFrEF
For patients with heart failure with reduced ejection fraction (HFrEF), only four beta-blockers are indicated: bisoprolol, carvedilol, sustained-release metoprolol succinate, and nebivolol. 1, 2
Evidence-Based Beta-Blockers
The following beta-blockers have proven mortality reduction in HFrEF and carry Class I, Level of Evidence A recommendations:
- Bisoprolol 1, 2
- Carvedilol 1, 2
- Sustained-release metoprolol succinate (NOT metoprolol tartrate) 1, 2
- Nebivolol 1
These recommendations come from the American Heart Association, American College of Cardiology, Heart Failure Society of America, and European Society of Cardiology. 2, 3
Target Dosing
Achieving target doses or at least 50% of target doses is critical for optimal outcomes: 2, 3
- Carvedilol: 25 mg twice daily (50 mg total daily dose) 2
- Metoprolol succinate: 200 mg once daily 2, 3
- Bisoprolol: 10 mg daily 4
Start at low doses and titrate gradually every 2 weeks as tolerated toward target doses. 3
Selection Between Beta-Blockers
Guidelines do not express a preference between carvedilol and metoprolol succinate, considering them equally effective. 2 However, patient-specific factors should guide selection:
- Pulmonary disease: Prefer bisoprolol, metoprolol, or nebivolol (more beta-1 selective) 5
- Diabetes: Prefer carvedilol or nebivolol 5
- Atrial fibrillation with rate control needs: Metoprolol is first choice, followed by bisoprolol, nebivolol, then carvedilol 3, 5
- Erectile dysfunction: Prefer bisoprolol or nebivolol 5
- Peripheral arterial disease: Prefer nebivolol 5
Critical Pitfalls to Avoid
Do NOT use non-evidence-based beta-blockers (such as atenolol or metoprolol tartrate) as they lack mortality benefit data in HFrEF. 2
Never abruptly discontinue beta-blockers as this leads to clinical deterioration. 2
Failure to titrate to target doses results in suboptimal outcomes - aim for at least 50% of target dose when full dose is not tolerated. 2, 3
Do not withhold beta-blockers in asymptomatic or mildly symptomatic HFrEF patients - they should be initiated in all eligible patients regardless of symptom severity. 2
Continue beta-blockers long-term even when symptoms improve - do not discontinue based on clinical improvement alone. 2, 3
Clinical Outcomes
Evidence-based beta-blocker use in HFrEF is associated with reduced heart failure readmissions and mortality between 8-365 days post-discharge. 6 The mortality benefit is substantial, with hazard ratios around 0.65-0.79 for long-term outcomes. 6