What is the use of amiodarone in adult patients with a history of cardiovascular disease and irregular heartbeats, such as atrial fibrillation and ventricular tachycardia?

Why Amiodarone Is Used

Amiodarone is primarily used for life-threatening ventricular arrhythmias (ventricular fibrillation and hemodynamically unstable ventricular tachycardia) refractory to other therapies, and secondarily for rate or rhythm control in atrial fibrillation when other agents are contraindicated or ineffective, particularly in patients with heart failure or structural heart disease. 1

FDA-Approved Indications

Amiodarone is FDA-approved specifically for:

• Initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation 1
• Hemodynamically unstable ventricular tachycardia in patients refractory to other therapy 1
• Treatment of patients with VT/VF for whom oral amiodarone is indicated but who cannot take oral medication 1

The intravenous formulation is intended for acute treatment until ventricular arrhythmias are stabilized, typically for 48-96 hours, though it may be safely administered for longer periods if necessary 1.

Life-Threatening Ventricular Arrhythmias

Primary Prevention and Secondary Prevention

For secondary prevention of sudden cardiac death:

• The North American Society for Pacing and Electrophysiology recommends amiodarone as the antiarrhythmic agent of choice in patients who have survived sustained ventricular tachyarrhythmias, particularly those with left ventricular dysfunction 2
• In patients with recurrent symptomatic ventricular tachycardia, 69% remained free of VT/VF recurrence during follow-up of 6-52 months on amiodarone therapy 3

For primary prevention:

• Meta-analysis showed amiodarone reduced annual mortality from 12.3% to 10.9% in patients with congestive heart failure or recent myocardial infarction (ARR 2.4%, NNT 42) 2
• The benefit was more pronounced in heart failure patients, reducing annual mortality from 24.3% to 19.9% (ARR 4.4%, NNT 23) 2
• However, implantable cardioverter-defibrillators (ICDs) are more effective than amiodarone in reducing mortality in high-risk patients with previous myocardial infarction 2

Role as Adjunct to ICD Therapy

Amiodarone serves as an important adjuvant drug:

• Reduces the frequency of ICD shocks in patients with implantable cardioverter-defibrillators 2
• Used to suppress recurrent ICD discharges when triggered by ventricular arrhythmias or atrial fibrillation 2
• Most likely to be safe and effective when antiarrhythmic therapy is necessary to prevent symptomatic ventricular arrhythmias 2

Atrial Fibrillation and Atrial Flutter

Rate Control Strategy

In acute atrial fibrillation with rapid ventricular response:

• Digoxin and amiodarone may be used for rate control in patients with congestive heart failure 2
• The potential risk of conversion to sinus rhythm with amiodarone should be considered before treating with this agent 2

In atrial flutter:

• Intravenous amiodarone can be useful for acute control of ventricular rate (in the absence of pre-excitation) in patients with systolic heart failure, when beta blockers are contraindicated or ineffective 2
• The therapeutic effect is likely mediated via blockade of beta receptors or calcium channels 2
• Amiodarone may be preferred in patients with reduced ventricular function or history of heart failure 2

Rhythm Control Strategy

For maintaining sinus rhythm:

• Amiodarone is the most powerful pharmacological agent for long-term sinus rhythm maintenance in patients with atrial fibrillation 4
• In one randomized controlled trial, sinus rhythm was maintained successfully for 16 months in 65% of patients treated with amiodarone, compared with 37% treated with sotalol or propafenone (ARR 28%, NNT 3.6) 2
• Amiodarone can be useful to maintain sinus rhythm in patients with symptomatic, recurrent atrial flutter, with drug choice depending on underlying heart disease and comorbidities 2

Critical caveat: Recent studies show that aggressive attempts to maintain sinus rhythm using amiodarone or other drugs do not improve outcomes in relatively asymptomatic patients 2. Therefore, long-term amiodarone therapy does not appear justified in patients taking anticoagulants if rate-control strategies provide satisfactory symptomatic improvement 2.

Focal Atrial Tachycardia

Intravenous amiodarone may be reasonable in the acute setting to:

• Restore sinus rhythm in hemodynamically stable patients with focal AT 2
• Slow the ventricular rate in hemodynamically stable patients with focal AT 2

This is a Class IIb recommendation with limited evidence (C-LD) 2.

Unique Pharmacological Properties

Amiodarone's effectiveness stems from its multi-class antiarrhythmic properties:

• Although classified as Class III, it affects all phases of the cardiac action potential 4, 5
• Shows antiarrhythmic properties of all four antiarrhythmic drug classes 4
• Potent coronary and peripheral vasodilator 4
• Can be safely used in patients with left ventricular dysfunction after myocardial infarction, congestive heart failure, or hypertrophic cardiomyopathy 4

Proarrhythmic profile:

• Regularly accompanied by QT and QTc-interval prolongation but rarely causes ventricular proarrhythmia 4
• This distinguishes it from other antiarrhythmics that have increased mortality in post-MI trials 2

Critical Limitations and When NOT to Use

Amiodarone should NOT be routinely used for:

• Patients with frequent premature ventricular depolarizations or asymptomatic nonsustained VT without heart failure 2
• Pre-excited atrial fibrillation, where AV nodal blocking agents like amiodarone may cause paradoxical increase in ventricular response 2

Long-term use concerns:

• Adverse drug reactions occur in 51% of patients on high-dose therapy 3
• Forced dose reduction in 41% and discontinuation in 10% of patients 3
• Most common adverse effects include tremor/ataxia (35%), nausea/anorexia (8%), visual disturbances (6%), thyroid dysfunction (6%), and pulmonary infiltrates (5%) 3
• Requires routine monitoring for thyroid, liver, and pulmonary toxicity 2, 5

Drug interactions:

• Extremely long half-life (averaging 58 days) means interactions persist for months after discontinuation 6
• Increases digoxin levels by 70% after one day, requiring 50% dose reduction 1
• Increases warfarin effect by 100% after 3-4 days, requiring one-third to one-half dose reduction 1
• Simvastatin should be limited to 20mg daily when co-administered with amiodarone 7

Practical Clinical Algorithm

For ventricular arrhythmias:

1. First-line: ICD for primary prevention in high-risk patients 2
2. Amiodarone as secondary prevention after survived VT/VF 2
3. Amiodarone as adjunct to ICD to reduce shock frequency 2

For atrial fibrillation:

1. First-line rate control: Beta blockers or calcium channel blockers in most patients 2
2. Amiodarone for rate control: Only in heart failure patients when other agents contraindicated 2
3. Amiodarone for rhythm control: Second-line in patients with structural heart disease or highly symptomatic patients without heart disease 2
4. Avoid in asymptomatic patients adequately anticoagulated where rate control suffices 2

Loading and maintenance:

• IV: 150mg bolus over 10 minutes, then 1mg/min for 6 hours, then 0.5mg/min for 18 hours 2
• Oral: 600-800mg daily in divided doses until 10g total given, then 200-400mg daily maintenance 2
• Use minimal doses for satisfactory arrhythmia outcome to reduce toxicity 4