Rate Control Agents for Atrial Fibrillation
Beta-blockers (metoprolol, atenolol) or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) are the recommended first-line agents for rate control in atrial fibrillation, with the choice primarily determined by left ventricular ejection fraction (LVEF). 1
Selection Algorithm Based on Cardiac Function
For Patients with LVEF ≥40% (Preserved Function)
First-line options include:
- Beta-blockers: Metoprolol 2.5-5 mg IV bolus over 2 minutes (up to 3 doses) acutely, or 25-100 mg orally twice daily for maintenance 1, 2
- Diltiazem: 0.25 mg/kg IV over 2 minutes acutely, then 5-15 mg/hour infusion; or 120-360 mg daily orally (divided doses or slow-release) for maintenance 1, 3
- Verapamil: 0.075-0.15 mg/kg IV over 2 minutes acutely, or 120-360 mg daily orally for maintenance 1
The evidence shows diltiazem achieves rate control faster than metoprolol, though both are safe and effective. 4 Beta-blockers and calcium channel blockers are superior to placebo and digoxin for controlling ventricular rate both at rest and during exercise. 1
For Patients with LVEF <40% or Heart Failure
Use the smallest dose of beta-blocker to achieve rate control as first-line therapy. 1 Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) must be avoided due to negative inotropic effects. 1
Second-line option:
- Digoxin: 0.25 mg IV every 2 hours up to 1.5 mg for loading, then 0.125-0.375 mg daily for maintenance 1, 5
For hemodynamically unstable patients or severely reduced LVEF:
- Amiodarone: 150 mg IV over 10 minutes, then 0.5-1 mg/min infusion; or 800 mg daily orally for 1 week, then taper to 200 mg daily 1, 3
Target Heart Rate
Initial target: <110 bpm at rest 1
For optimal control, aim for 60-80 bpm at rest and 90-115 bpm during moderate exercise. 3, 2 This "lenient" rate control strategy (<110 bpm) is appropriate for most patients as the initial goal. 1
Critical Contraindications and Precautions
Avoid diltiazem/verapamil in:
- Heart failure with reduced ejection fraction (LVEF ≤40%) 3
- AV block greater than first degree without pacemaker 3
- Wolff-Parkinson-White syndrome with AF 3
- Hypotension 3
Avoid beta-blockers in:
- Severe bradycardia 1
- Second or third-degree AV block without pacemaker 2
- Decompensated heart failure 2
- Active asthma 1
Digoxin: Limited Role
Digoxin should only be used as a second-line agent because it is effective only for rate control at rest, not during exercise. 1 It is most appropriate for:
- Physically inactive elderly patients (≥80 years) 6
- Add-on therapy when beta-blockers or calcium channel blockers alone are insufficient 1
- Patients with heart failure as adjunctive therapy 1
Despite observational studies associating digoxin with excess mortality, this likely reflects selection bias rather than drug harm, as digoxin is prescribed to sicker patients. 1
Combination Therapy
If monotherapy fails to achieve target heart rate, add digoxin to the initial beta-blocker or calcium channel blocker. 1 Combinations of digoxin plus diltiazem, atenolol, or betaxolol are effective at rest and with exercise. 1
Amiodarone is suggested as adjunctive therapy only when combination therapy with standard agents fails to achieve rate control. 1
Prognostic Considerations
Beta-blockers remain first-line across all AF patients despite meta-analysis data showing they do not reduce all-cause mortality in AF patients with heart failure with reduced ejection fraction (HR 0.97; 95% CI 0.83-1.14), unlike their clear benefit in sinus rhythm. 1 They are still recommended based on symptomatic improvement, lack of harm, and good tolerability. 1