Patients with AF and stable CAD often face difficult treatment choices balancing ischemic and bleeding risks. The EPIC-CAD randomized trial, published in Heart, evaluated whether off-label underdosing of edoxaban alters outcomes compared to standard dosing.

Of 1040 participants, 694 without dose-reduction criteria were analyzed, and 121 (17.4%) received a low dose of 30 mg daily. At 12 months, the composite outcome of — death, myocardial infarction, stroke, systemic embolism, revascularization, or bleeding occurred at— similar rates in the standard-dose and underdosed groups (10.5% vs 9.2%). Ischemic events (1.4% vs 1.7%) and bleeding (9.0% vs 8.4%) also showed no significant differences.

Importantly, the benefit of edoxaban monotherapy over dual therapy was consistent regardless of dose. However, the trial was underpowered, and wide confidence intervals mean the findings should be interpreted with caution.