What are the medications for atrial fibrillation (AF)?

Medications for Atrial Fibrillation

For AF management, medications fall into three main categories: rate control agents (beta-blockers, non-dihydropyridine calcium channel blockers, digoxin), rhythm control agents (amiodarone, flecainide, propafenone, sotalol, dofetilide, ibutilide), and anticoagulants (warfarin, DOACs including apixaban and rivaroxaban). 1

Rate Control Medications

Beta-blockers and non-dihydropyridine calcium channel blockers are first-line agents for rate control, targeting heart rate <100 bpm. 1

Beta-Blockers

• Metoprolol tartrate: 2.5-5 mg IV bolus over 2 minutes (up to 3 doses); oral maintenance 25-100 mg twice daily 1
• Metoprolol XL (succinate): 50-400 mg once daily orally 1
• Atenolol: 25-100 mg once daily orally 1
• Esmolol: 500 mcg/kg IV bolus over 1 minute, then 50-300 mcg/kg/min IV infusion 1
• Propranolol: 1 mg IV over 1 minute (up to 3 doses at 2-minute intervals); oral 10-40 mg three to four times daily 1
• Carvedilol: 3.125-25 mg twice daily orally 1
• Bisoprolol: 2.5-10 mg once daily orally 1

Beta-blockers achieved rate control endpoints in 70% of patients in the AFFIRM study, superior to calcium channel blockers at 54%. 1 They provide better control of exercise-induced tachycardia than digoxin and are particularly useful in high adrenergic states. 1 Initiate cautiously in patients with heart failure and reduced ejection fraction. 1

Non-Dihydropyridine Calcium Channel Blockers

• Verapamil: 0.075-0.15 mg/kg IV bolus over 2 minutes (may give additional 10 mg after 30 minutes); oral 180-480 mg once daily (extended release) 1
• Diltiazem: 0.25 mg/kg IV bolus over 2 minutes, then 5-15 mg/hour infusion; oral 120-360 mg once daily (extended release) 1

These agents are the only rate control drugs associated with improvement in quality of life and exercise tolerance. 1 Avoid or use cautiously in patients with heart failure due to systolic dysfunction because of negative inotropic effects. 1

Digoxin

• Digoxin: 0.25 mg IV with repeat dosing to maximum 1.5 mg over 24 hours; oral maintenance 0.125-0.25 mg once daily 1
• Loading dose: 0.5 mg orally daily for 2 days, then 0.125-0.375 mg daily 1

Amiodarone for Rate Control

• Amiodarone (Class IIb recommendation): 300 mg IV over 1 hour, then 10-50 mg/hour over 24 hours; oral loading 800 mg daily for 1 week, then maintenance 200 mg daily 1
• Useful when other rate control measures are unsuccessful or contraindicated 1

Rhythm Control Medications

For Pharmacological Cardioversion (Acute Conversion)

Flecainide, dofetilide, propafenone, and IV ibutilide are Class I recommendations for pharmacological conversion of AF when contraindications are absent. 1

• Ibutilide: Generally effective in 30-90 minutes but carries higher risk of QT prolongation and torsades de pointes 1
• IV amiodarone: Requires several hours for efficacy 1
• Avoid IV procainamide for patients initially treated with amiodarone or ibutilide to prevent excessive QT prolongation 1

For Maintenance of Sinus Rhythm

Drug selection depends on presence or absence of structural heart disease. 1

Patients WITHOUT Structural Heart Disease (No or Minimal)

First-line agents: Flecainide, propafenone, and sotalol - generally well tolerated and devoid of extracardiac organ toxicity 1

• Flecainide and propafenone: Should be combined with AV nodal blocking agents (calcium channel blocker or beta-blocker) to prevent rapid ventricular response if AF converts to atrial flutter 1
• Contraindications for flecainide: Severe left ventricular hypertrophy, heart failure with reduced ejection fraction, or coronary artery disease 2

Second-line agents: Amiodarone, disopyramide, procainamide, quinidine - greater potential for adverse reactions 1

Patients WITH Heart Failure

Amiodarone or dofetilide are first-line choices based on safety data 1

Patients WITH Coronary Artery Disease

Sotalol is first-line (combines beta-blocking activity with antiarrhythmic efficacy) unless patient has heart failure 1

• Amiodarone and dofetilide are secondary agents 1

Patients WITH Hypertension Without LVH

Flecainide and propafenone are first-line (do not prolong QT interval, offering safety advantage) 1

• Secondary choices: Amiodarone, dofetilide, sotalol 1

Patients WITH Left Ventricular Hypertrophy (≥1.4 cm wall thickness)

Amiodarone is first-line therapy due to relative safety compared to other agents in hypertrophied myocardium prone to proarrhythmic toxicity 1

Antiarrhythmic Drug Initiation Considerations

Most antiarrhythmic drugs (except beta-blockers and amiodarone) should be initiated in hospital. 1

• Monitor ECG parameters: PR interval (flecainide, propafenone, sotalol, amiodarone), QRS duration (flecainide, propafenone), QT interval (sotalol, amiodarone, disopyramide) 1
• Start at low dose with upward titration, reassessing ECG with each dose change 1
• Dofetilide: Current standards do not permit out-of-hospital initiation 1

Pretreatment Before Cardioversion

Starting antiarrhythmic therapy before electrical cardioversion enhances immediate success and suppresses early recurrences. 1

Effective agents that enhance DC cardioversion and prevent immediate recurrence: Amiodarone, flecainide, ibutilide, propafenone, quinidine, sotalol (Class I, Level of Evidence B) 1

Anticoagulation

All patients with AF and elevated stroke risk (CHA₂DS₂-VASc ≥2) require oral anticoagulation regardless of rate or rhythm control strategy. 3

Direct Oral Anticoagulants (DOACs) - Preferred Over Warfarin

Apixaban:

• Standard dose: 5 mg orally twice daily 4
• Reduced dose: 2.5 mg twice daily if patient has ≥2 of: age ≥80 years, body weight ≤60 kg, serum creatinine ≥1.5 mg/dL 4
• Superior to warfarin in reducing stroke and systemic embolism (HR 0.79,95% CI 0.66-0.95, p=0.01) 4

Rivaroxaban:

• 20 mg once daily (15 mg once daily if CrCl 30-50 mL/min) 5
• For patients with CrCl 15-30 mL/min, observe closely for bleeding; avoid if CrCl <15 mL/min 5

Warfarin: Target INR 2.0-3.0 1

• Requires ≥3 weeks of therapeutic anticoagulation before cardioversion and ≥4 weeks after 1

Post-Cardiac Surgery AF Management

Short-term prophylactic beta-blockers or amiodarone (Class 2a recommendation) for high-risk patients undergoing CABG, aortic valve, or ascending aortic aneurysm operations. 1

For established post-operative AF:

• Rate control with beta-blocker or calcium channel blocker when safe from surgical bleeding 1
• Direct current cardioversion with antiarrhythmic therapy if hemodynamically unstable 1
• 30-60 day postoperative rhythm assessment with cardioversion if AF persists 1

Critical Pitfalls to Avoid

• Never use IV verapamil or diltiazem in AF with pre-excitation (accelerates conduction over accessory pathway) 1
• Avoid class IC drugs (flecainide, propafenone) in structural heart disease - increased mortality risk 1, 6
• Monitor for torsades de pointes with sotalol, especially at treatment initiation 6
• Amiodarone requires monitoring for pulmonary toxicity, thyroid dysfunction, corneal deposits, optic neuropathy, and warfarin interactions 1
• NSAIDs increase bleeding risk in anticoagulated patients 3
• Diltiazem and verapamil inhibit CYP3A4, potentially affecting other drug metabolism 3