Clinically Important Drug–Drug Interactions Between Antiarrhythmic Drugs and Anticoagulants

Until the last decade, vitamin K antagonists (VKAs) were the only agents available for oral anticoagulation. Although effective and accessible, their use was complicated by a narrow therapeutic window, the need for regular monitoring of the international normalized ratio, and an associated susceptibility to interactions with both food and numerous medications. Furthermore, the onset of action was delayed, often requiring bridging with intravenous agents. In more recent years, we have enjoyed the development of nonvitamin-K-dependent, direct oral anticoagulants (DOACs), which either directly inhibit the activity of factor IIa (eg, dabigatran) or factor Xa (eg, rivaroxaban, apixaban, edoxaban). These medications boast a more rapid onset of action, predictable pharmacokinetics, wider therapeutic window, and equal or superior safety profiles. Although these medications appear to have fewer drug-drug interactions than VKAs, their interactions remain of clinical importance, particularly in one of the largest populations requiring anticoagulation: patients with atrial fibrillation. These patients are rarely on single medications, with the majority of them requiring some form of rate or rhythm control due to their arrhythmia. Unfortunately, data on interactions between DOACs and antiarrhythmic medications, despite their common coadministration, remain limited. Here, we summarize the interactions between antiarrhythmics and VKAs and review existing knowledge regarding their interactions with DOACs.