Beta-Blockers in Heart Failure with Reduced Ejection Fraction
Beta-blockers are a Class I, Level A recommendation for all patients with HFrEF and must be prescribed alongside an ACE inhibitor (or ARNI) to reduce mortality and heart failure hospitalizations. 1
Evidence-Based Beta-Blocker Selection
Only three beta-blockers have proven mortality benefit in HFrEF and should be used exclusively 1, 2:
- Bisoprolol
- Carvedilol
- Metoprolol succinate (sustained-release)
Guidelines do not express preference between these agents, considering them equally effective based on major clinical trials 2. However, recent real-world data suggests carvedilol may provide superior survival compared to metoprolol succinate (adjusted HR 1.069 for metoprolol vs carvedilol, 95% CI: 1.046-1.092), with 6-year survival of 55.6% vs 49.2% respectively 3.
Target Dosing Strategy
Clinicians must titrate to evidence-based target doses (or at least 50% of target) to maximize mortality benefit 1:
- Carvedilol: 25 mg twice daily (50 mg total daily) 2
- Metoprolol succinate: 200 mg once daily 2
- Bisoprolol: Target doses per clinical trials 1
Start at very low doses and increase gradually every 2 weeks if tolerated 1. Real-world data shows only 26.6% of patients achieve maximal target doses, representing a significant treatment gap 4. Patients receiving maximally titrated beta-blockers have significantly reduced hazard of death or major adverse cardiac events (HR 0.43) compared to incomplete titration 4.
Timing of Initiation
Outpatient/Stable HFrEF
Begin beta-blocker therapy immediately upon diagnosis in all patients with current or prior symptoms of HFrEF, unless contraindicated 1, 2.
Acute Decompensated Heart Failure
Continue beta-blockers in patients already on therapy during hospitalization for acute decompensation 5. Withdrawal is associated with increased in-hospital and short-term mortality 5.
For beta-blocker naive patients hospitalized with acute decompensated heart failure, initiate at low dose only after 1:
- Volume status optimized
- Intravenous diuretics, vasodilators, and inotropes successfully discontinued
- Patient hemodynamically stable 5
Integration with Contemporary HFrEF Therapy
Beta-blockers remain a foundational pillar of guideline-directed medical therapy alongside 1:
- ACE inhibitor (or ARNI as replacement to further reduce mortality) 1
- Mineralocorticoid receptor antagonist for persistent symptoms 1
- SGLT2 inhibitors (newer addition to therapy)
The introduction of SGLT2 inhibitors may facilitate better beta-blocker up-titration by improving hemodynamic tolerance 4.
Critical Contraindications and Cautions
Absolute avoidance 1:
- Diltiazem or verapamil (non-dihydropyridine calcium channel blockers) increase heart failure worsening and hospitalization risk 1
Use with extreme caution 6:
- Overt decompensated heart failure with ongoing need for inotropes
- Severe bradycardia or high-degree heart block
- Bronchospastic disease (use lowest dose of bisoprolol if necessary, with bronchodilator available) 6
- Peripheral vascular disease (may precipitate arterial insufficiency) 6
Common Pitfalls to Avoid
Never abruptly discontinue beta-blockers 2, 6. Sudden cessation can precipitate exacerbation of angina, myocardial infarction, or ventricular arrhythmias 6. If withdrawal is necessary, taper over approximately one week under careful observation 6.
Do not use non-evidence-based beta-blockers (e.g., atenolol, propranolol) as they lack proven mortality benefit in HFrEF 2.
Avoid undertitration 1. Failure to reach target doses results in suboptimal outcomes, yet this remains widespread in clinical practice with only 26.6% achieving maximal doses 4. Make every effort to achieve target doses shown effective in major clinical trials 1.
Do not withhold beta-blockers due to comorbidities 7. Prognostic benefit remains relevant in patients with diabetes, atrial fibrillation, pulmonary disease, and peripheral arterial disease—these are not contraindications 7. Select the most appropriate agent for specific comorbidities (e.g., bisoprolol or nebivolol for pulmonary disease, carvedilol for diabetes) 7.
Monitoring During Titration
Assess at each dose escalation 1: