Antiarrhythmic Treatment in Atrial Fibrillation

Seema Ledan, PharmD


US Pharmacist. 2020;45(2):24-27. 

In This Article


Antiarrhythmic agents work by blocking the sodium, potassium, and calcium channels or the adrenergic receptors. The Vaughan Williams classification system defines where the arrhythmic agents work: Class I agents are sodium-channel blockers, class II are beta-blockers, class III are potassium-channel blockers, and class IV are calcium-channel blockers.[11]

Vaughan Williams Class IA

Quinidine and disopyramide are class IA antiarrhythmic agents that work on the sodium channel. The use of these agents has decreased and is not recommended as first-line. Although quinidine was one of the first antiarrhythmic agents used in AF, it is now reserved as an alternative treatment when newer antiarrhythmics are contraindicated.[1] Quinidine may prolong QT interval and can cause torsades de pointes. Disopyramide can also prolong QT interval and is avoided in structural heart disease. Although disopyramide is useful in a high vagal tone setting, there is little evidence available to help support this use.[1] A systematic review also suggested that quinidine and disopyramide may increase mortality.[12]

Vaughan Williams Class IC

Flecainide and propafenone are class IC agents working on the sodium channel. Due to results from the Cardiac Arrhythmia Suppression Trial (CAST) study, these agents are not recommended in patients with concomitant left ventricular dysfunction and coronary artery disease. Flecainide is very effective in treating AF and premature ventricular contractions that are triggered in patients with structurally normal hearts; use is not recommended in those with structural heart disease. In addition, the chance of proarrhythmic toxicity increases with exertion when heart rate increases.[11] Propafenone is indicated for more severe or life-threatening ventricular arrhythmias and should be used in conjunction with atrioventricular nodal blocking agents because of the possibility of conversion to atrial flutter. The absorption of both agents may be altered with food, especially with milk for flecainide.[11]

Vaughan Williams Class III

Amiodarone, dofetilide, dronedarone, and sotalol are class III agents, potassium channel blockers that lead to prolongation of QT interval and possible ventricular arrhythmias or torsades de pointes. Amiodarone is considered the most potent antiarrhythmic agent.[11]

The adverse event profile with amiodarone can be intolerable, with gastrointestinal effects the most common side effect.[11,13] Other side effects that may occur include pulmonary inflammation, thyroid abnormalities, retinal deposits, and congestive and inflammatory hepatopathy.[11] Amiodarone may also cause a decrease in pro-arrhythmic effects and effectiveness in maintenance of sinus rhythm compared with other antiarrhythmic agents.[14] Dronedarone, an analogue of amiodarone, is less efficacious than amiodarone but has an improved side effect profile. Sotalol and dofetilide are effective in the maintenance of sinus rhythm, but inpatient loading is recommended. Both have also been shown to be effective in preventing arrhythmia in patients with underlying structural heart disease.[11] Of all antiarrhythmic agents, dofetilide and amiodarone have been proven safe in patients with heart failure.[11]