Amiodarone for Recurrent Paroxysmal Atrial Fibrillation
Primary Recommendation
For adult patients with recurrent paroxysmal atrial fibrillation and structural heart disease (heart failure, coronary artery disease, left ventricular hypertrophy, or prior MI), amiodarone is the preferred first-line antiarrhythmic agent due to its superior efficacy and low proarrhythmic risk; however, for patients without structural heart disease, amiodarone should only be used as second-line therapy after failure of Class IC agents (flecainide, propafenone) or sotalol, due to significant extracardiac toxicity and increased non-cardiac mortality. 1, 2, 3
Patient Selection Algorithm
Step 1: Assess for Structural Heart Disease
Patients WITH structural heart disease (heart failure, CAD, LVH, prior MI): Amiodarone is first-line 1, 2, 3
Patients WITHOUT structural heart disease: Avoid amiodarone as first-line 1, 3
Step 2: Verify No Contraindications
Exclude amiodarone if patient has: 1
- Sinus or AV conduction disease without pacemaker
- Inflammatory lung disease
- Hepatic dysfunction
- Active thyroid disease (hypothyroidism or hyperthyroidism)
- Peripheral neuropathy
- Optic neuritis
Dosing Strategy
Loading Phase
Standard loading regimen: 1, 2
- 400-600 mg daily in divided doses for 2-4 weeks, then transition to maintenance
- Alternative: 600 mg/day for 1 month OR 1000 mg/day for 1 week 2
- Another option: 800 mg daily × 1 week → 600 mg daily × 1 week → 400 mg daily × 4-6 weeks 2
Maintenance Phase
Target the lowest effective dose to minimize toxicity: 1, 2, 3
- Standard maintenance: 200 mg daily 1, 2
- Low-dose option: 100-200 mg daily is often equally effective with fewer side effects 1, 2
- For elderly or high-risk patients: 100 mg daily 2
- Some patients may require up to 400 mg daily, but keep at lowest effective dose 1, 2
Evidence for low-dose efficacy:
- Low-dose amiodarone (50-100 mg daily) maintained sinus rhythm in 90% at 6 months, 83.3% at 12 months, and 72.7% at 24 months in elderly patients 5
- Overall long-term efficacy of 79% with maintenance doses of 200-400 mg/day 6
Efficacy Data
Rhythm Control
- Amiodarone vs. sotalol: 60% vs. 38% maintained sinus rhythm 1, 2
- Amiodarone vs. Class I agents: 62% vs. 23% maintained sinus rhythm at 1 year 1, 2
- Median time to AF recurrence: 487 days with amiodarone vs. 74 days with sotalol vs. 6 days with placebo 1
- In patients with ischemic heart disease specifically, amiodarone (569 days) and sotalol (428 days) showed similar time to recurrence 1
Cardioversion Enhancement
- Increases success rate of electrical cardioversion 1, 2
- 83% remained in sinus rhythm at 6 months post-cardioversion vs. 43% with quinidine 1, 2
- Spontaneous conversion occurred in 27% with amiodarone vs. 24% with sotalol vs. 0.8% with placebo after 28-day loading 1
Mandatory Monitoring Requirements
Baseline Assessment 1, 2, 3
- Liver function tests
- Thyroid function tests (TSH, free T4)
- Pulmonary function tests and chest X-ray
- Ophthalmologic examination
- ECG (assess QT interval, heart rate, conduction)
Ongoing Monitoring 1, 2, 3
- Liver and thyroid function tests: Every 6 months minimum 2, 3
- ECG monitoring for QT prolongation and bradycardia 2
- Ophthalmologic examination for corneal deposits 2
- Pulmonary symptoms assessment at each visit 3
Critical Toxicity Concerns
Extracardiac Toxicities 1, 3, 7
Pulmonary toxicity:
- Occurs in 1-2% annually with doses ≤300 mg/day 3
- Can progress to adult respiratory distress syndrome (potentially fatal) 1, 3
- May develop years after treatment initiation 7
Thyroid dysfunction:
Hepatotoxicity:
- Monitor liver enzymes regularly 1, 2, 3
- Can cause hepatocellular necrosis with IV loading at excessive rates 8
Other toxicities:
- Peripheral neuropathy (significant concern with long-term use) 1, 3
- Corneal microdeposits (usually asymptomatic) 1, 2, 3
- Optic neuritis 1
- Photosensitivity 9
- Gastrointestinal upset 1, 9
Cardiac Toxicities 1
- Bradycardia
- QT prolongation (though torsades de pointes is rare) 1
- AV block
Mortality Risk
- In patients WITHOUT structural heart disease: Increased all-cause mortality (HR 2.41) and non-cardiac mortality (HR 3.55) 4
- Non-cardiovascular death more frequent with amiodarone than rate control strategy in AFFIRM trial 7
- Severe or fatal outcomes may occur years after initiation and are often not attributed to amiodarone by prescribers 7
Drug Interactions
Amiodarone is a potent inhibitor of multiple pathways: 1
- CYP2C9 (moderate), CYP2D6 (moderate), CYP3A4 (weak)
- P-glycoprotein inhibitor
- OCT2 inhibitor
Critical dose adjustments required: 1
- Warfarin: Reduce dose by 50%
- Digoxin: Reduce dose by 30-50%
- Avoid with dofetilide (contraindicated)
- Multiple other significant interactions with anticoagulants, statins, and other cardiovascular drugs 1
Common Pitfalls to Avoid
Using amiodarone first-line in patients without structural heart disease - This increases mortality risk without clear benefit 4, 3
Failing to use lowest effective maintenance dose - Higher doses increase toxicity without proportional efficacy benefit 1, 2, 3
Inadequate long-term monitoring - Toxicities can develop years after initiation and are often underestimated 7
Not considering catheter ablation - In young patients without structural heart disease, ablation should be considered before amiodarone 3
Prescriber specialization matters - Amiodarone use as first-line decreased from 31% (primary care) to 22% (general cardiology) to 9% (electrophysiology), suggesting overuse by less specialized providers 4
Forgetting drug interactions - Particularly with warfarin and digoxin, which require dose reductions 1
Alternative Consideration
Catheter ablation should be considered before amiodarone in: 3
- Young patients with paroxysmal AF
- Patients without structural heart disease
- Patients seeking to avoid long-term medication toxicity
- This reduces symptoms, recurrence, and AF progression 3