What medications are used to treat paroxysmal atrial fibrillation?

Medications for Paroxysmal Atrial Fibrillation

For patients with lone paroxysmal atrial fibrillation without structural heart disease, flecainide (200-300 mg/day), propafenone (450-900 mg/day), or sotalol (240-320 mg/day) are first-line antiarrhythmic agents, with beta-blockers as an alternative initial option. 1

Drug Selection Based on Clinical Context

Patients Without Structural Heart Disease (Lone AF)

First-line options:

• Flecainide 200-300 mg/day or propafenone 450-900 mg/day are particularly effective 1
• Sotalol 240-320 mg/day is equally effective 1
• Beta-blockers may be tried first, especially in exercise-induced AF 1

Second-line options:

• Amiodarone 100-400 mg/day (after loading) is recommended as alternative therapy but should be chosen later due to potential toxicity 1
• Dofetilide 500-1000 mcg/day (dose-adjusted for renal function) 1

Not favored unless other options fail:

• Quinidine, procainamide, and disopyramide 1

Patients With Structural Heart Disease, Heart Failure, or LVEF <40%

Only safe options:

• Amiodarone 100-400 mg/day is the preferred agent due to low proarrhythmic risk in this population 1, 2
• Dofetilide 500-1000 mcg/day (requires in-hospital initiation with dose adjustment for renal function and QT monitoring) 1

Patients With Coronary Artery Disease

• Sotalol is preferred over amiodarone due to lower toxicity, with equal effectiveness 1
• Amiodarone remains appropriate if sotalol is not tolerated 1

Trigger-Specific Considerations

Vagally-induced AF:

• Disopyramide 400-750 mg/day is relatively attractive due to anticholinergic activity 1
• Avoid propafenone (weak beta-blocking activity may aggravate vagal AF) 1

Adrenergically-mediated AF:

• Beta-blockers are first-line treatment 1
• Followed by sotalol then amiodarone 1

Comparative Efficacy Data

Amiodarone demonstrates superior efficacy:

• Maintains sinus rhythm in 69% vs 39% with propafenone or sotalol at 16 months 1
• In AFFIRM substudy: 62% maintained sinus rhythm at 1 year vs 23% with class I agents 1
• However, 18% discontinued due to side effects (vs 11% with sotalol/propafenone) 1

Flecainide efficacy:

• Median time to first recurrence: 14.5 days vs 3 days on placebo 3
• Prevented AF in 31% vs 9% on placebo over study period 3
• When combined with metoprolol: reduces recurrences to 66.7% vs 46.8% with flecainide alone in persistent AF 4

Dofetilide efficacy:

• Maintained sinus rhythm in 58% at 1 year vs 25% placebo (SAFIRE-D) 1
• In patients with LV dysfunction: 79% vs 42% placebo (DIAMOND) 1

"Pill-in-the-Pocket" Strategy

For selected patients with infrequent, symptomatic episodes and no structural heart disease:

• Self-administer single oral dose of flecainide or propafenone at symptom onset 5, 2
• Requires initial in-hospital conversion trial to verify safety 5, 2
• Must exclude: sinus node/AV dysfunction, bundle branch block, prolonged QT, Brugada syndrome, structural heart disease 5, 2
• Critical requirement: Beta-blocker or non-dihydropyridine calcium antagonist must be given ≥30 minutes before class IC agent (or as ongoing therapy) to prevent rapid AV conduction if conversion to atrial flutter occurs 5, 2, 6

This approach is NOT appropriate for frequent episodes (e.g., weekly); these patients require continuous prophylactic therapy 2

Combination Therapy

When single-drug therapy fails:

• Useful combinations include beta-blocker, sotalol, or amiodarone PLUS a type IC agent (flecainide or propafenone) 1
• Flecainide-metoprolol combination significantly improves outcomes in persistent AF 4, 7

Critical Monitoring Requirements

Type IC drugs (flecainide, propafenone):

• QRS widening must not exceed 150% of baseline 1
• Exercise testing helpful to detect use-dependent conduction slowing 1
• FDA Warning: Flecainide carries mortality risk in post-MI patients (CAST trial: 5.1% vs 2.3% placebo) 6
• Risk of 1:1 AV conduction in atrial flutter; requires concomitant AV nodal blocking agent 6

Type IA/III drugs (except amiodarone):

• Corrected QT interval must remain <520 ms 1
• Dofetilide: Must initiate in-hospital with dose titration to renal function; 0.8% risk of torsades de pointes (mostly in first 3 days) 1
• Sotalol: Dose adjustment required for renal function; risk of torsades de pointes, bradycardia, heart failure exacerbation 1, 8

All antiarrhythmics:

• Monitor potassium ≥4.0 mEq/L and magnesium levels 1, 2
• Check renal function periodically (renal insufficiency increases drug accumulation and proarrhythmia risk) 1
• Reassess LV function if clinical heart failure develops 1

Anticoagulation - Mandatory Consideration

All patients with CHA₂DS₂-VASc score ≥2 require oral anticoagulation regardless of rhythm control success 5, 2

• Direct oral anticoagulants (DOACs) preferred over warfarin (60-80% lower intracranial hemorrhage) 5
• Continue indefinitely even if episodes cease 2

Common Pitfalls to Avoid

• Never use class IC agents in patients with structural heart disease, heart failure, or post-MI (increased mortality risk) 6
• Never use flecainide or propafenone without concomitant AV nodal blockade (risk of 1:1 flutter conduction) 5, 2, 6
• Do not use amiodarone as first-line in patients without structural heart disease (toxicity risk: pulmonary, thyroid, hepatic, ocular) 1, 2
• Avoid antiarrhythmics in advanced conduction disorders without pacing 5, 2
• Do not stop anticoagulation after cardioversion or prolonged sinus rhythm (stroke risk persists) 2
• Alert patients about drugs that prolong QT interval (see torsades.org) 1
• Monitor for proarrhythmia when patients develop new CAD or heart failure (initially safe drugs may become dangerous) 1