What medications are used to treat Atrial Fibrillation (AFib)?

Medications for Atrial Fibrillation

Atrial fibrillation management requires three medication categories: anticoagulation to prevent stroke, rate control agents to manage ventricular response, and rhythm control drugs to restore and maintain sinus rhythm—with anticoagulation being mandatory for most patients regardless of rhythm strategy. 1

Anticoagulation Therapy (Stroke Prevention)

All patients with AF require stroke risk assessment using CHA₂DS₂-VASc score, with anticoagulation recommended for scores ≥2 and considered for scores ≥1. 1, 2

Direct Oral Anticoagulants (DOACs) - Preferred

• Apixaban, rivaroxaban, edoxaban, or dabigatran are preferred over warfarin due to 60-80% stroke risk reduction compared to placebo and lower bleeding risks than warfarin 2, 3
• DOACs reduce stroke risk by the same magnitude as warfarin but with improved safety profile 3

Warfarin (Vitamin K Antagonist)

• Target INR 2.0-3.0 for most patients 1
• Target INR 2.5-3.5 or higher for prosthetic heart valves, prior thromboembolism, or persistent atrial thrombus 1
• Requires INR monitoring weekly during initiation, then monthly when stable 1

Critical Anticoagulation Principles

• Anticoagulation must continue based on stroke risk even after successful rhythm control or cardioversion—this is a common and dangerous pitfall 2
• Aspirin is NOT recommended for stroke prevention in AF due to inferior efficacy compared to anticoagulation 3
• For cardioversion: anticoagulate ≥3 weeks before and ≥4 weeks after if AF duration ≥48 hours or unknown 1

Rate Control Medications

Beta-blockers and non-dihydropyridine calcium channel blockers are first-line agents for rate control in patients with preserved left ventricular function (LVEF >40%). 1, 4, 2

Beta-Blockers (First-Line for Most Patients)

Beta-blockers are the most effective drug class for rate control, achieving heart rate endpoints in 70% of patients compared to 54% with calcium channel blockers. 4

Intravenous Formulations:

• Metoprolol tartrate: 2.5-5 mg IV bolus over 2 minutes; up to 3 doses 1
• Esmolol: 500 mcg/kg IV bolus over 1 minute, then 50-300 mcg/kg/min infusion 1
• Propranolol: 1 mg IV over 1 minute, up to 3 doses at 2-minute intervals 1

Oral Formulations:

• Metoprolol tartrate: 25-100 mg twice daily 1
• Metoprolol XL (succinate): 50-400 mg once daily 1
• Atenolol: 25-100 mg once daily 1
• Carvedilol: 3.125-25 mg twice daily 1
• Bisoprolol: 2.5-10 mg once daily 1

Beta-blockers provide superior exercise heart rate control compared to digoxin and are first-line for thyrotoxicosis-induced AF. 4, 2

Non-Dihydropyridine Calcium Channel Blockers

Diltiazem:

• IV: 0.25 mg/kg IV bolus over 2 minutes, then 5-15 mg/hour infusion 1
• Oral: 120-360 mg once daily (extended release) 1
• Preferred for patients with COPD and AF 4

Verapamil:

• IV: 0.075-0.15 mg/kg IV bolus over 2 minutes; may give additional 10 mg after 30 minutes if no response, then 0.005 mg/kg/min infusion 1
• Oral: 180-480 mg once daily (extended release) 1

Digoxin (Limited Role)

Digoxin should NOT be used as sole agent for rate control in active patients—it is only effective at rest. 1, 5

• IV: 0.25 mg IV with repeat dosing to maximum 1.5 mg over 24 hours 1
• Oral: 0.125-0.25 mg once daily 1
• Appropriate for sedentary patients, heart failure, or LV dysfunction 1
• Combination therapy with beta-blocker or calcium channel blocker is reasonable to control rate at rest and during exercise 1

Amiodarone (Rate Control - Special Circumstances)

Intravenous amiodarone is recommended when diltiazem is at maximum dose with inadequate rate control or when other measures are unsuccessful. 1, 6

• IV: 300 mg over 1 hour, then 10-50 mg/hour over 24 hours (or 900 mg IV over 24 hours via central line) 1, 6
• Oral: 100-200 mg once daily 1

Rate Control Strategy Based on Cardiac Function

For LVEF ≤40% (reduced ejection fraction): use beta-blockers and/or digoxin ONLY—avoid calcium channel blockers due to negative inotropic effects. 1, 4, 2

For LVEF >40% (preserved function): beta-blockers or calcium channel blockers are both appropriate first-line choices. 1, 4, 2

Rate Control Targets

• Lenient control: resting heart rate <110 bpm is the initial target 6, 2
• Stricter control (<80 bpm) reserved for patients with persistent AF-related symptoms despite lenient control 6, 2

Rhythm Control Medications (Cardioversion and Maintenance)

Acute Pharmacological Cardioversion

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

For Structurally Normal Hearts:

• Flecainide or propafenone are first-line for cardioversion 2, 7
• These agents have the lowest proarrhythmic risk and organ toxicity when used together in normal hearts 8

For Structural Heart Disease or Reduced LVEF:

• Amiodarone is the preferred agent 2, 5

Chronic Rhythm Maintenance

Selection of antiarrhythmic drugs for maintaining sinus rhythm is guided primarily by cardiac structure and function, NOT by efficacy (as most drugs have similar efficacy). 8

No Structural Heart Disease (Normal Heart):

First-choice agents: dronedarone, flecainide, propafenone, or sotalol 5

• Class IC agents (flecainide, propafenone) have lowest proarrhythmic risk in structurally normal hearts 8
• Propafenone is indicated to prolong time to recurrence of paroxysmal AF associated with disabling symptoms 7

Structural Heart Disease with LVEF >35%:

Dronedarone, sotalol, or amiodarone 5

Heart Failure with LVEF <35%:

Amiodarone is the ONLY drug usually recommended 5

• Amiodarone has low proarrhythmic risk but can produce bradyarrhythmias and organ toxicity 8

Critical Safety Considerations

Class I antiarrhythmic drugs (flecainide, propafenone) should be AVOIDED in ischemic heart disease or conditions with impaired cell contact (fibrosis, infiltration) due to greatly increased risk of sustained ventricular arrhythmias. 8

Class III/IA agents carry enhanced risk of torsades de pointes in hypertrophied hearts. 8

Sotalol adverse effects are dose-related and include bradycardia, QT prolongation, and proarrhythmia—with torsades de pointes being a serious concern. 9

Special Clinical Scenarios

AF with Pre-excitation (Accessory Pathway)

Avoid beta-blockers, calcium channel blockers, and digoxin—use procainamide or ibutilide instead. 1, 6

• Immediate cardioversion required if hemodynamically unstable 1

AF with Acute Coronary Syndrome

Beta-blockers are recommended for patients without heart failure, hemodynamic instability, or bronchospasm. 4

Hemodynamically Unstable AF

Immediate electrical cardioversion is required—do not delay for pharmacological therapy. 1, 2

"Pill-in-the-Pocket" Approach

Intermittent antiarrhythmic therapy may be considered for symptomatic patients with infrequent, longer-lasting AF episodes as alternative to daily therapy. 5

Common Pitfalls to Avoid

• Never withdraw anticoagulation based on rhythm control success—stroke risk persists due to silent AF recurrences 2
• Never use digoxin as monotherapy in active patients—it only controls resting heart rate 1, 5
• Never use calcium channel blockers in reduced LVEF—risk of hemodynamic compromise 4, 2
• Never use Class I drugs in ischemic or fibrotic hearts—high ventricular arrhythmia risk 8
• Monitor continuously when using multiple rate-controlling agents—risk of excessive bradycardia and hypotension 6
• Target lenient rate control initially (<110 bpm)—stricter control only if symptoms persist 6, 2