What are the indications, dosing, contraindications, adverse effects, monitoring recommendations, and alternative therapies for bisoprolol (a selective β1‑adrenergic blocker)?

Bisoprolol: Clinical Overview

Indications

Bisoprolol is indicated for heart failure with reduced ejection fraction (HFrEF), hypertension, and angina pectoris, with the strongest evidence supporting its use in HFrEF where it reduces all-cause mortality by 34%. 1

Heart Failure with Reduced Ejection Fraction

• Bisoprolol is one of only three beta-blockers proven to reduce mortality in HFrEF (alongside carvedilol and metoprolol succinate) 1
• In CIBIS-II, bisoprolol reduced all-cause mortality from 17.3% to 11.8% (RR 0.66,95% CI 0.54-0.81, P<0.001), with a number needed to treat of 23 patients for 1 year to prevent 1 death 1, 2
• Sudden death was reduced by 44% (RR 0.56,95% CI 0.39-0.80, P=0.001) 1
• All-cause hospital admissions were reduced by 20% (hazard ratio 0.80,95% CI 0.71-0.91, P<0.001) 1, 2

Perioperative Cardiac Risk Reduction

• Bisoprolol is recommended for patients undergoing high-risk surgery (Class I, Level B) and should be considered for intermediate-risk surgery (Class IIa, Level B) 1
• In the DECREASE IV trial, bisoprolol reduced perioperative cardiac events from 6.0% to 2.1% (HR 0.34,95% CI 0.17-0.67) 1

Hypertension and Angina

• Bisoprolol is effective for hypertension and stable angina, though not first-line for uncomplicated hypertension 1, 3, 4

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Dosing

Heart Failure with Reduced Ejection Fraction

Starting dose: 1.25 mg once daily 1, 5

Titration schedule: Double the dose every 2-4 weeks if tolerated 1, 5

• 1.25 mg → 2.5 mg → 5 mg → 10 mg once daily 5

Target dose: 10 mg once daily 1, 5

Key principle: Even if the target dose cannot be achieved, maintaining the highest tolerated dose is recommended—some bisoprolol is better than no bisoprolol 1, 5

Perioperative Use

• Start with 2.5 mg daily, initiated optimally between 30 days and at least 1 week before surgery 1
• Titrate to achieve resting heart rate 60-70 beats/min with systolic blood pressure >100 mmHg 1

Hypertension

• Starting dose: 2.5-5 mg once daily 1, 5
• Target dose: 10 mg once daily (maximum 20 mg daily, though doses above 10 mg provide limited additional benefit) 5, 6

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Contraindications

Absolute Contraindications

• Asthma (true severe asthma, not COPD) 1
• Second- or third-degree heart block without a permanent pacemaker 1
• Sick sinus syndrome without a permanent pacemaker 5
• Sinus bradycardia <50 beats/min with symptoms 1, 5
• Symptomatic hypotension 1
• Current or recent (within 4 weeks) decompensated heart failure requiring hospitalization 1, 5

Important Clarifications

• COPD is NOT a contraindication: Given its high β1-selectivity, bisoprolol is the only beta-blocker specifically not contraindicated in COPD 1
• Peripheral artery disease is NOT a contraindication: Worsening of intermittent claudication has not been shown to occur more frequently in randomized trials 1

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Adverse Effects

Common Adverse Effects

• Dizziness 2
• Bradycardia 2
• Hypotension 2
• Fatigue 2

Less Common Than Placebo

• Worsening heart failure 2
• Dyspnea 2
• Tachycardia 2

Tolerability

• In CIBIS-II, there was no significant difference between bisoprolol and placebo in permanent treatment withdrawal 1, 2
• Bisoprolol is generally well tolerated with a favorable side-effect profile 2, 4

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Monitoring Recommendations

During Initiation and Titration

Monitor at 1-2 weeks after each dose increase: 1, 5

• Heart rate (target >50 beats/min) 1, 5
• Blood pressure (systolic >100 mmHg) 1, 5
• Clinical status, especially signs of congestion 1, 5
• Body weight (daily weights; increase diuretic if weight increases by 1.5-2.0 kg over 2 consecutive days) 1, 5

Long-Term Monitoring

• Blood chemistry 12 weeks after initiation and 12 weeks after final dose titration 5

Management of Adverse Effects During Titration

For worsening congestion: 1, 5

1. First: Double the diuretic dose
2. Second: Halve the bisoprolol dose only if increasing diuretic fails

For marked fatigue or bradycardia: 1, 5

• Halve the bisoprolol dose

For heart rate <50 beats/min with worsening symptoms: 1, 5

• Halve the dose or stop if severe deterioration

For symptomatic hypotension: 1, 5

• First reconsider need for vasodilators (nitrates, calcium channel blockers)
• Then reduce diuretic if no congestion present
• Only then consider reducing bisoprolol dose

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Critical Clinical Pearls

Never Abruptly Discontinue

Bisoprolol must never be stopped abruptly due to risk of rebound ischemia, myocardial infarction, and ventricular arrhythmias. 1, 5

Tapering protocol when discontinuation is necessary: 5

• Reduce dose by 25-50% every 7 days under close surveillance
• Example: 10 mg → 5 mg (week 1) → 2.5 mg (week 2) → 1.25 mg (week 3) → stop (week 4)
• Exercise extreme caution in patients with coronary artery disease 5

Continuation in Specific Scenarios

• Continue bisoprolol when prescribed for ischemic heart disease, arrhythmias, or hypertension perioperatively (Class I, Level C) 1
• In decompensated heart failure, bisoprolol may need to be reduced or temporarily omitted, but ideally non-cardiac surgery should be deferred until stable 1

Dose-Response Relationship

• Higher doses confer greater mortality benefit based on dose-response data 1, 5
• At least 50% of target dose (5 mg daily minimum) should be achieved to obtain mortality benefits 5

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Alternative Therapies

Other Evidence-Based Beta-Blockers for HFrEF

Only three beta-blockers have proven mortality reduction in HFrEF—this is not a class effect: 1, 5

1. Carvedilol 1, 5

   • Starting: 3.125 mg twice daily
   • Target: 25-50 mg twice daily (25 mg for <85 kg, 50 mg for ≥85 kg)
   • Provides combined α1 and β-blockade with additional vasodilation
   • 65% mortality reduction in US Carvedilol Heart Failure Program 1

2. Metoprolol succinate extended-release 1, 5, 7

   • Starting: 12.5-25 mg once daily
   • Target: 200 mg once daily
   • Critical: Only metoprolol succinate (not tartrate) has proven mortality benefit 1, 5, 7
   • 34% mortality reduction in MERIT-HF 1

When to Choose Bisoprolol Over Alternatives

• COPD patients: Bisoprolol is specifically not contraindicated due to high β1-selectivity 1
• Once-daily dosing preference: Bisoprolol offers consistent 24-hour coverage with 10-12 hour half-life 3, 4
• Balanced hepatic and renal clearance: 50% hepatic, 50% renal—may offer advantages in patients with isolated hepatic or renal impairment 3, 4

Non-Beta-Blocker Alternatives for Specific Scenarios

In patients with true asthma or COPD with positive bronchoreactivity where beta-blockers are contraindicated: 1

• Ivabradine (for heart rate reduction)
• Diltiazem or verapamil (for heart rate control, though not in HFrEF with reduced ejection fraction)

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Pharmacokinetic Advantages

• High oral bioavailability: 90% 3, 4
• Long elimination half-life: 10-12 hours, allowing once-daily dosing 3, 4
• Balanced clearance: 50% hepatic metabolism, 50% renal excretion 3, 4
• High β1-selectivity: Much greater inhibition of exercise tachycardia compared to inhibition of isoprenaline-induced falls in diastolic blood pressure (unlike propranolol) 4
• No intrinsic sympathomimetic activity or membrane-stabilizing activity 2, 3, 4