You will see antiarrhythmics used in clinical practice. They are typically prescribed by cardiovascular specialists, but we wanted to provide an antiarrhythmic comparison chart because as a healthcare professional, you still need to monitor for risks and drug interactions associated with these medications.

Patients can develop arrhythmias through a variety of cardiac and non-cardiac factors. The most common cause of arrhythmia is due to structural heart diseases such as ischemia or MI. However, valve disorders, hypertension, and heart failure may also lead to arrhythmias. Patients may also develop arrhythmias due to electrolyte imbalances, especially potassium and magnesium, as well as from illicit drug use. It is important to check patients with arrhythmias for electrolyte imbalances or the presence of illicit drugs which are both reversible causes of arrhythmia. 

The most common arrhythmia is atrial fibrillation. However, patients may also have atrial flutter, sinus tachycardia, or supraventricular tachycardia. Ventricular arrhythmias tend to be more serious and include premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation. Ventricular tachycardia can be classified as pulse or pulseless. Pulseless VTach is a medical emergency and should be treated using the ACLS algorithm. We’ve noted in the antiarrhythmic comparison chart below that some medications are used in ACLS. Ventricular fibrillation is life-threatening and always a medical emergency. Although antiarrhythmic agents are used to treat arrhythmias, the majority are also proarrhythmic, and therefore should be used with caution. Many of the antiarrhythmics have serious box warnings associated with them. Risk/benefit analysis should be done before deciding to initiate an antiarrhythmic agent. 

Antiarrhythmic agents are most commonly classified using the Vaughan-Williams (VM) classification system, which is based on the mechanism of action. Some agents fall into multiple classes of mechanisms. Class I are sodium channel blockers and can be further broken down into Ia, Ib, and Ic. Class I agents are negative inotropes and proarrhythmic. Class II agents refer to beta-blockers, which are often first-line agents for rate control. Class III agents are potassium channel blockers. Many of these agents are also proarrhythmic. Amiodarone and dofetilide are the agents of choice for heart failure. Class IV agents are non-dihydropyridine calcium channel blockers, which are used for rate control. Digoxin is another common antiarrhythmic that is not part of the Vaughan-Williams classification system. Digoxin works by inhibiting the Na/K/ATPase. Digoxin is often used as add-on therapy for rate control if beta-blockers or non-DHP CCBs are inadequate or unable to be used. We’ve noted the classes of each agent in the antiarrhythmic comparison chart below.

Agent	Class	Boxed Warnings	Clinical Pearls
disopyramide	Class Ia	Life threatening ventricular arrhythmias only	anticholinergic
quinidine	Class Ia	May increase mortality in Afib or Aflutter; control AV node conduction before initiating.	Risk for hemolysis, drug-induced lupus erythematosus, high incidence of diarrhea/stomach cramps, can cause cinchonism (quinine overdose syndrome)
procainamide	Class Ia	Agranulocytosis. Can cause positive antinuclear antibody test with or without drug induced lupus erythematosus. Life threatening ventricular arrhythmias only
lidocaine	Class Ib	none	Used for refractory ventricular tachycardia or cardiac arrest. Part of the ACLS algorithm. Caution in elderly, hepatic impairment, heart failure.
mexiletine	Class Ib	Can cause acute liver injury, especially in patients with CHF or ischemia. Life threatening ventricular arrhythmias only	Caution in elderly, hepatic impairment, heart failure.
flecainide	Class Ic	Life threatening ventricular arrhythmias only. Can have ventricular proarrhythmic effects when treating Afib or Aflutter. Can cause 1:1 atrioventricular conduction; negative chronotropes reduce risk	Contraindicated in structural heart disease (heart failure, MI, etc)
propafenone	Class Ic	Life threatening ventricular arrhythmias only	Beta blocking effects. Contraindicated in structural heart disease (heart failure, MI, etc)
amiodarone	Class III	Proarrhythmic. Life threatening arrhythmias only. Pulmonary toxicity. Hepatotoxicity.	Drug of choice in heart failure. Rate and rhythm control. Contains iodine. Can cause hypothyroidism, optic neuropathy, photosensitivity, peripheral neuropathy, SJS/TEN, teratogenic. Get baseline CXR, PFT, LFTs. Monitor ECG, BP, HR, LFT, TSH/T4, electrolytes.  Moderate CYP2C9, P-gp inhibitor. Weak CYP3A4 and P-gp inhibitor. Substrate of CYP3A4, 2C8, and P-gp. Reduce doses of digoxin, warfarin, and simvastatin when starting amiodarone.
dronedarone	Class III	Contraindicated due to increased mortality in NYHA IV HF or recent HF decompensation. Contraindicated in Afib patients who cannot/will not be cardioverted. Increased mortality in permanent Afib.	Contraindicated with strong CYP3A4 inhibitors QT prolongation Can cause liver injury and interstitial lung disease (pulmonary fibrosis, pneumonitis)
sotalol	Class III	Dose increase and titration must be done in hospital with continuous ECG monitoring. Life threatening VTach due to QT prolongation can occur. Do not initiate if QTc >450. If QTc>500, reduce or discontinue	Non-selective beta blocker. Adjust dose based on CrCl. If CrCl < 60, reduce interval. If CrCl<40 contraindicated in Afib (can still be used in ventricular arrhythmias with reduced interval)
ibutilide	Class III	Proarrhythmic. Weigh risks/benefits of NSR. Can cause VTach and QT prolongation
dofetilide	Class III	Must be initiated in hospital with continuous ECG monitoring. QT prolongation. Do not use if QTc>440.	Drug of choice in heart failure. Assess CrCl for at least 3 days. Proarrhythmic.
diltiazem	Class IV	none	Rate control only. Negative inotrope; contraindicated in HFrEF. Contraindicated in hypotension (SBP<90), 2nd or 3rd degree heart block. CYP3A4 and P-gp substrate. CYP3A4 inhibitor. Avoid grapefruit.
verapamil	Class IV	none	Rate control only. Negative inotrope; contraindicated in HFrEF. Contraindicated in hypotension (SBP<90), 2nd or 3rd degree heart block. CYP3A4 and P-gp substrate. CYP3A4 inhibitor. Avoid grapefruit.
digoxin	other	none	Rate control. Usually second line after beta blocker or non-DHP CCB. Can cause N/V, bradycardia, blurred vision, impaired green/yellow vision, arrhythmias. Monitor levels. Goal: 0.8-2 ng/mL.

The article was written by Melody Grafton in collaboration with Eric Christianson, PharmD, BCGP, BCPS

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References:

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