What is the recommended beta‑blocker regimen for rate control in atrial fibrillation, including initial oral dosing, titration, target heart rate, contraindications, and alternative agents if beta‑blockers are unsuitable?

Beta-Blocker Regimen for Rate Control in Atrial Fibrillation

Beta-blockers are first-line agents for rate control in atrial fibrillation, with metoprolol being the preferred agent due to its favorable safety profile and efficacy at rest and during exercise. 1, 2

Initial Oral Dosing

Metoprolol (Preferred Agent)

• Start metoprolol 25–100 mg orally twice daily as the initial maintenance dose after acute rate control is achieved. 1
• For acute intravenous control before transitioning to oral therapy, give metoprolol 2.5–5 mg IV bolus over 2 minutes, up to 3 doses, with onset of action in 5 minutes. 1, 2

Alternative Beta-Blockers

• Bisoprolol 1.25–20 mg once daily (or split dosing). 1
• Carvedilol 3.125–50 mg twice daily. 1
• Atenolol 25–100 mg once daily. 3
• Propranolol 80–240 mg daily in divided doses (onset 60–90 minutes). 1

Titration Strategy

• Titrate the beta-blocker dose every 4–7 days based on heart rate response and symptom control. 3
• Assess heart rate during physical activity as well as at rest, because many patients have inadequate rate control during exertion despite acceptable resting rates. 1
• If symptomatic bradycardia (<50 bpm) or high-grade AV block occurs, reduce the dose immediately. 3

Target Heart Rate

• Aim for a lenient resting heart rate goal of <110 bpm as the initial target for most patients with preserved left ventricular function. 1, 3, 2
• Pursue stricter control (<80 bpm) only if symptoms persist despite achieving the lenient target. 1, 3
• The RACE II trial demonstrated that lenient rate control was non-inferior to strict control for clinical outcomes in patients with preserved ejection fraction. 3

Combination Therapy When Monotherapy Fails

• Add digoxin 0.0625–0.25 mg daily to the beta-blocker if adequate rate control is not achieved within 4–7 days of optimal beta-blocker dosing. 1, 3
• Combination therapy with digoxin plus beta-blocker provides superior heart-rate control both at rest and during exercise compared with either drug alone. 1, 3
• Monitor closely for bradycardia when combining agents, as the risk of excessive AV nodal blockade increases. 1, 3

Contraindications to Beta-Blockers

Absolute Contraindications

• Active bronchospasm or severe asthma (though beta-1 selective agents like bisoprolol or metoprolol may be cautiously used in mild COPD). 1
• Decompensated heart failure with pulmonary congestion or cardiogenic shock. 1, 2
• High-grade AV block (second- or third-degree) without a pacemaker. 1
• Severe bradycardia (<50 bpm) or symptomatic hypotension. 1

Relative Contraindications Requiring Caution

• Overt congestion or hypotension in patients with heart failure with reduced ejection fraction (HFrEF), though beta-blockers remain indicated once stabilized. 1, 2
• Peripheral vascular disease (may worsen claudication). 1

Alternative Agents When Beta-Blockers Are Unsuitable

For Patients with Preserved Ejection Fraction (>40%)

• Non-dihydropyridine calcium channel blockers are the preferred alternative:
  • Diltiazem 120–360 mg daily (60 mg three times daily or once-daily modified release). 1, 2
  • Verapamil 120–360 mg daily (40–120 mg three times daily or once-daily modified release). 1
• For acute IV control: Diltiazem 0.25 mg/kg IV over 2 minutes, followed by 5–15 mg/h infusion (onset 2–7 minutes). 1, 2

For Patients with Reduced Ejection Fraction (≤40%) or Heart Failure

• Digoxin is the only safe alternative when beta-blockers are contraindicated, as calcium channel blockers have negative inotropic effects and may worsen hemodynamics. 1, 2
• Digoxin dosing: 0.0625–0.25 mg daily orally (loading dose 0.5 mg daily for 2 days if needed). 1
• Digoxin alone is ineffective for rate control during exercise or sympathetic surges and should be combined with a beta-blocker whenever possible. 3, 2, 4

For Chronic Obstructive Pulmonary Disease or Active Bronchospasm

• Non-dihydropyridine calcium channel blockers (diltiazem or verapamil) are preferred over beta-blockers to avoid bronchospasm. 1, 2
• Beta-1 selective agents (bisoprolol, metoprolol) in small doses may be cautiously considered if calcium channel blockers are insufficient, but avoid non-selective beta-blockers (carvedilol, propranolol). 1

Last-Resort Options

• Amiodarone may be considered when rate control cannot be achieved with combination therapy (beta-blocker or calcium channel blocker plus digoxin), but it is reserved as a second- or third-line agent due to significant extracardiac toxicity (pulmonary fibrosis, hepatic injury, thyroid dysfunction). 1, 5, 2
• AV node ablation with pacemaker implantation should be considered when maximal pharmacologic rate control fails or is not tolerated. 1, 3

Common Pitfalls to Avoid

• Do not use digoxin as monotherapy in paroxysmal atrial fibrillation, as it is ineffective during exercise or high sympathetic tone. 3, 2, 4
• Avoid calcium channel blockers (diltiazem, verapamil) in patients with LVEF ≤40% or decompensated heart failure, as they may precipitate hemodynamic collapse. 1, 2
• Do not combine beta-blockers with diltiazem or verapamil except under specialist supervision, as the risk of severe bradycardia and heart block is substantial. 1, 3
• In Wolff-Parkinson-White syndrome with pre-excited atrial fibrillation, avoid all AV-nodal blocking agents (beta-blockers, calcium channel blockers, digoxin, adenosine, amiodarone), as they may accelerate ventricular rate and precipitate ventricular fibrillation. 1, 3, 2
• Assess heart rate during exertion, not just at rest, because resting rate control does not guarantee adequate control during activity. 1
• When combining amiodarone with digoxin, reduce the digoxin dose by approximately 50% and monitor serum digoxin levels closely to avoid toxicity. 5