How should beta‑blockers be initiated and titrated in a euvolemic patient with systolic heart failure on stable diuretics and ACE‑I/ARB/ARNI therapy, with resting heart rate >60 bpm and systolic blood pressure >90 mmHg, and what are the contraindications and monitoring parameters?

Beta-Blocker Therapy in Systolic Heart Failure

All patients with stable heart failure with reduced ejection fraction (HFrEF) should receive one of three evidence-based beta-blockers—bisoprolol, carvedilol, or metoprolol succinate—initiated at low doses and titrated every 2 weeks to target doses proven to reduce mortality by 34-35%. 1

Evidence-Based Beta-Blocker Selection

Only three beta-blockers have demonstrated mortality reduction in HFrEF and should be used exclusively 1, 2:

• Bisoprolol: Start 1.25 mg once daily → target 10 mg once daily 1, 2
• Carvedilol: Start 3.125 mg twice daily → target 25-50 mg twice daily 1, 2, 3
• Metoprolol succinate (extended-release only): Start 12.5-25 mg once daily → target 200 mg once daily 1, 2

Critical distinction: Metoprolol tartrate (immediate-release) and bucindolol have NOT demonstrated mortality benefit and should never be used for heart failure. 1, 2 Short-acting metoprolol tartrate was less effective in clinical trials, and this is not a class effect. 1

Patient Selection Criteria

Initiate beta-blockers immediately once HFrEF is diagnosed in stable patients, even if symptoms are mild or already improved with other therapies. 1 The mortality benefit occurs regardless of symptom improvement. 1

Required stability criteria 1:

• Not hospitalized in intensive care unit
• No or minimal fluid overload (euvolemic on stable diuretics)
• No recent intravenous inotropic therapy
• Resting heart rate >60 bpm
• Systolic blood pressure >90 mmHg

You do NOT need 1:

• High-dose ACE inhibitor therapy before starting beta-blocker (adding beta-blocker to low-dose ACE inhibitor produces greater mortality reduction than increasing ACE inhibitor dose) 1
• Complete symptom resolution
• Weeks of stability after hospital discharge

Initiation and Titration Protocol

Start at very low doses and double every 2 weeks if tolerated, monitoring closely at each step. 1, 2

Standard titration schedule 2:

Bisoprolol: 1.25 mg → 2.5 mg → 5 mg → 10 mg once daily (every 2 weeks) 2

Carvedilol: 3.125 mg → 6.25 mg → 12.5 mg → 25 mg twice daily (every 2 weeks) 2, 3
Take with food to reduce orthostatic effects 3

Metoprolol succinate: 12.5 mg → 25 mg → 50 mg → 100 mg → 200 mg once daily (every 2 weeks) 2

Monitoring at each titration 2:

• Heart rate and blood pressure
• Signs of congestion (weight, edema, lung examination)
• Symptoms of fatigue or dizziness
• Blood chemistry 1-2 weeks after initiation and after final dose

Delay dose increases until adverse effects from lower doses resolve. 1 Approximately 85% of patients can achieve target doses with this cautious approach. 1

Target Doses and Mortality Benefit

Make every effort to achieve target doses used in clinical trials, as these produced 34-35% reductions in all-cause mortality. 1, 2 However, if target doses cannot be tolerated, aim for at least 50% of target dose—some beta-blocker is better than no beta-blocker. 2

Even if symptoms do not improve, maintain long-term treatment to reduce risk of sudden death and disease progression. 1

Absolute Contraindications

Do not initiate beta-blockers in 1:

• Current or recent (within 4 weeks) decompensated heart failure requiring hospitalization
• Patients requiring intravenous inotropic therapy
• Second- or third-degree heart block without pacemaker
• Symptomatic bradycardia (<50 bpm with symptoms)
• Symptomatic hypotension
• Active asthma with persistent symptoms

Relative contraindications (use cautiously): Reactive airway disease or asymptomatic bradycardia may be considered with close monitoring. 1

Managing Adverse Reactions

Four main adverse reactions require management 1:

1. Fluid retention/worsening heart failure:

• First: Double diuretic dose 2
• Second: Halve beta-blocker dose only if increasing diuretic fails 2
• This is NOT a reason for permanent withdrawal 1

2. Fatigue:

• Halve beta-blocker dose 2
• Slow rate of uptitration

3. Bradycardia (<50 bpm with worsening symptoms):

• Halve beta-blocker dose 2
• If severe deterioration, seek specialist advice before stopping 2

4. Symptomatic hypotension:

• First: Reduce or eliminate nitrates, calcium channel blockers, other vasodilators 2
• Second: Reduce diuretic dose if no congestion present 2
• Third: Halve beta-blocker dose only if above measures fail 2
• Asymptomatic low blood pressure requires no adjustment 2

Critical Pitfalls to Avoid

Never abruptly withdraw beta-blockers—this can cause clinical deterioration, rebound myocardial ischemia, infarction, and arrhythmias. 1, 2 If discontinuation is necessary, taper gradually over approximately one week under close observation. 2

Do not delay beta-blocker initiation until ACE inhibitors are at target doses or until symptoms return after initial improvement. 1 Beta-blockers should be started as soon as HFrEF is diagnosed in stable patients. 1

Do not prescribe beta-blockers without diuretics in patients with current or recent fluid retention—diuretics are essential to prevent exacerbation of fluid retention during beta-blocker initiation. 1

Do not use metoprolol tartrate (immediate-release) for heart failure—only metoprolol succinate (extended-release) has proven mortality benefit. 1, 2

Background Therapy Requirements

Beta-blockers should be added to 1:

• Diuretics (mandatory if any history of fluid retention) 1
• ACE inhibitor, ARB, or ARNI (standard background therapy) 1
• Digoxin (if already prescribed) 1

The combination of beta-blockers with ACE inhibitors produces additive mortality benefits through dual neurohormonal blockade. 1

Long-Term Management

Continue beta-blocker therapy indefinitely to maintain mortality benefit and prevent disease progression. 1 Even patients with minimal symptoms should remain on therapy. 1

Instruct patients to weigh themselves daily and increase diuretic dose if weight increases by 1.5-2.0 kg over 2 consecutive days. 2