What alternatives can replace bisoprolol (Beta-blocker) in patients requiring replacement?

How to Replace Bisoprolol

When replacing bisoprolol in patients with heart failure with reduced ejection fraction (HFrEF), switch to either carvedilol or sustained-release metoprolol succinate, as these are the only other beta-blockers with proven mortality reduction in this population. 1

Evidence-Based Beta-Blocker Alternatives

Only three beta-blockers have demonstrated mortality reduction in large-scale trials for HFrEF and are recommended by ACC/AHA guidelines 1:

• Bisoprolol (target dose 10 mg once daily)
• Carvedilol (target dose 25 mg twice daily for patients <85 kg, 50 mg twice daily for patients ≥85 kg)
• Metoprolol succinate (sustained-release) (target dose 200 mg once daily)

Critical caveat: The beta-blocker benefit is NOT a class effect. 1 Other beta-blockers like bucindolol failed to show mortality benefit, and immediate-release metoprolol tartrate (commonly prescribed but wrong formulation) was not the formulation proven effective in mortality trials. 1

Specific Replacement Strategies by Clinical Indication

For Heart Failure with Reduced Ejection Fraction (HFrEF)

Primary alternatives:

• Carvedilol: Start at 3.125 mg twice daily, titrate every 2 weeks to target dose of 25 mg twice daily (or 50 mg twice daily if ≥85 kg). 1 Carvedilol showed a 65% mortality reduction in the US Carvedilol Heart Failure Program and 35% reduction in COPERNICUS trial for advanced heart failure. 1

• Metoprolol succinate (sustained-release): Start at 12.5-25 mg once daily, titrate every 2 weeks to target dose of 200 mg once daily. 1 MERIT-HF demonstrated 34% reduction in all-cause mortality. 1

Important distinction: One head-to-head trial (COMET) showed carvedilol reduced mortality more than immediate-release metoprolol tartrate, but this was NOT the sustained-release metoprolol succinate formulation proven effective in MERIT-HF. 1 The relative efficacy between carvedilol and metoprolol succinate at their proven target doses remains unknown. 1

For Post-Myocardial Infarction

Guideline-recommended alternatives: 1

• Carvedilol or metoprolol succinate should be used in patients with LV systolic dysfunction (EF ≤40%) with heart failure or prior MI. 1
• Beta-blocker therapy should continue for at least 3 years in all patients with normal LV function after MI/ACS. 1

For Hypertension or Rate Control

Broader alternatives available: 2, 3

• Metoprolol succinate: 50-100 mg once daily (approximately equivalent to bisoprolol 5 mg). 2
• Atenolol: 50 mg once daily (approximately equivalent to bisoprolol 5 mg). 2, 3 Start at 50 mg daily, maximum 100 mg daily for hypertension. 3
• Nebivolol: Consider for hypertension, though it has intrinsic sympathomimetic activity which may diminish efficacy in heart failure. 4, 5

Practical Switching Protocol

When switching from bisoprolol to another beta-blocker: 6

1. Do NOT abruptly discontinue bisoprolol - taper over 1-2 weeks when possible, especially in patients with coronary artery disease, to avoid rebound angina, MI, or ventricular arrhythmias. 4

2. Start replacement beta-blocker at LOW initial doses while tapering bisoprolol:

   • Carvedilol: 3.125 mg twice daily 1
   • Metoprolol succinate: 12.5-25 mg once daily 1
   • Atenolol: 25-50 mg once daily 3

3. Titrate gradually every 2 weeks to target doses if tolerated. 1

4. Monitor closely for: 1

   • Bradycardia (heart rate <60 bpm)
   • Hypotension (systolic BP <85 mmHg)
   • Worsening heart failure symptoms
   • Fluid retention

Dose Equivalency Reference

Approximate equivalent doses to bisoprolol 5 mg: 2

• Metoprolol succinate: 50-100 mg once daily
• Atenolol: 50 mg once daily
• Carvedilol: 12.5 mg twice daily

Target doses for HFrEF: 1

• Bisoprolol: 10 mg once daily
• Carvedilol: 25 mg twice daily (<85 kg) or 50 mg twice daily (≥85 kg)
• Metoprolol succinate: 200 mg once daily

Special Populations Requiring Dose Adjustment

Renal impairment: 3

• For atenolol with creatinine clearance 15-35 mL/min: maximum 50 mg daily
• For creatinine clearance <15 mL/min: maximum 25 mg daily
• Patients on hemodialysis: give 25-50 mg after each dialysis under supervision

Elderly patients: 3

• Start at lower end of dosing range (e.g., atenolol 25 mg daily)
• Assess renal function before initiating therapy
• Titrate more cautiously

Common Pitfalls to Avoid

Do not use these beta-blockers for HFrEF: 1, 5

• Immediate-release metoprolol tartrate (wrong formulation)
• Atenolol (no mortality data in HF)
• Bucindolol (failed to show benefit)
• Nebivolol (intrinsic sympathomimetic activity diminishes efficacy)
• Any beta-blocker with intrinsic sympathomimetic activity

Contraindications requiring alternative therapy: 4

• Severe bronchospastic disease (consider alternative antihypertensive class)
• Decompensated heart failure requiring IV inotropes (stabilize first)
• Severe bradycardia or heart block without pacemaker
• Cardiogenic shock