Ultra-low-dose direct oral anticoagulants in vulnerable patients with atrial fibrillation or coronary artery disease

Direct oral anticoagulants (DOACs) have largely supplanted warfarin for stroke prevention in atrial fibrillation due to their superior safety and efficacy profiles. Although standard dosing regimens are well-established, lower doses—often referred to as ultra‐low-dose (ULD) DOACs—have been investigated in selected populations to balance thrombotic and bleeding risks. The concept of ULD DOACs was first introduced in the 2013 European Heart Rhythm Association Practical Guide specifically for post‐acute coronary syndrome patients with residual thrombotic risk. Clinical trials, including ATLAS ACS-TIMI 51 and COMPASS, demonstrated that rivaroxaban 2.5 mg twice a day reduced ischemic events when combined with aspirin, although this benefit was accompanied by an increased risk of major bleeding. Similarly, the ELDERCARE-AF trial revealed that edoxaban 15 mg once a day effectively prevented stroke in frail older patients. Conversely, evidence supporting ULDs of dabigatran and apixaban remains limited. Despite their potential benefits, inappropriate dose reductions based on subjective physician judgment rather than rigorous clinical guidelines may result in suboptimal anticoagulation and a heightened risk of thromboembolic events. This review explores the indications, supporting evidence, and potential risks associated with ULD DOACs, underscoring the need for well-designed studies to establish clear guidelines.