The importance of dosing frequency on the safety of DOACs.

Direct oral anticoagulants (DOACs) represent a significant advance over vitamin K antagonists, such as warfarin in patients with atrial fibrillation (AF), due to their favorable risk-benefit profile, with significant reductions in stroke and serious bleeding, particularly intracranial hemorrhage.1 Although as class, DOACs tend to reduce major bleeding in general compared to warfarin, they are associated with a significant excess of gastrointestinal (GI) bleeding. A rationale for this observation is that unlike warfarin, the DOACs are active anticoagulants in the gastrointestinal lumen which contributes to GI bleeding above and beyond the systemic exposure to anticoagulant activity. Ido et al. present an interesting study in this issue investigating whether dosing regimen, specifically once vs. twice daily, is the major contributor to a differential GI bleeding profile across the DOACs.