Selecting the appropriate AV blocking agent requires the knowledge of other indications and contraindications for these drugs; specifically, knowledge of the left ventricular systolic function is important. AV blocking agents used in atrial fibrillation include beta-blockers, non-dihydropyridine calcium channel blockers and digoxin.

Beta-blockers (atenolol, metoprolol, carvedilol and others) antagonize beta-receptors (see review of beta-adrenergic blockers), which results in decreasing conduction through the AV node, reducing the heart rate in patients with AF. Caution is advised in patients with asthma since antagonizing beta-2 receptors can cause bronchospasm. In severe left ventricular systolic dysfunction (reduced ejection fraction), beta-blockers can acutely decrease cardiac output, leading to severe hypotension, acute heart failure and even cardiogenic shock. Despite this, beta-blockers are considered safe when used cautiously in this setting.

Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) decrease AV conduction by antagonizing voltage gated calcium channels decreasing intracellular calcium. Since these drugs reduce left ventricular inotropy (contractility) via the same mechanism, they are in general not advised to be used in the setting of left ventricular systolic dysfunction (reduced ejection fraction).

Digoxin blocks the sodium/potassium ATPase pump. The mechanism by which this decreases AV conduction is not clear; however, it is perhaps due to increased vagal tone. Intracellular calcium within the cardiac myocytes is increased by digoxin, resulting in increased inotropy (contractility), and thus digoxin is frequently used when AF and left ventricular systolic dysfunction coexist. Digoxin is effective to reduce ventricular rates at rest; however, it is not effective during physical activity, and thus it is recommended to use digoxin in combination with a beta-blocker or non-dihydropyridine calcium channel blocker.

Rarely, the above medications are not able to adequately reduce the ventricular rate and AV nodal ablation with permanent pacemaker implantation is needed.