Direct oral anticoagulants in very elderly and high bleeding risk patients with atrial fibrillation often excluded from oral anticoagulation therapy: a nationwide population-based cohort study

Background and Aims In the Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial, very low-dose edoxaban (15 mg once daily) showed better efficacy and positive net clinical benefit compared to placebo in very elderly, high bleeding risk patients with atrial fibrillation (AF). However, there is limited data to generalize these results into daily practice. We aimed to investigate the optimal OAC strategy for the best net clinical benefit in ELDERCARE-AF-like patients. Methods We used the Korean nationwide claims database to identify AF patients aged ≥ 80 years from 2014 to 2017 who had one or more ELDERCARE-AF trial inclusion criteria. The risks of ischemic stroke, major bleeding, all-cause death, and net clinical outcome were evaluated. Primarily, we compared patients without OAC therapy (non-OAC group) to patients with direct oral anticoagulants (DOAC group), using a propensity score weighting method. Results A total of 23,858 patients were included (no OAC: 16,575; warfarin: 2,390; DOAC: 4,893). Among DOAC group, 69% used low-dose and 9% used very low-dose. Compared to the non-OAC group, the DOAC group showed lower risks of ischemic stroke (hazard ratio, 95% confidence interval: 0.81, 0.68-0.96) and all-cause death (0.91, 0.86-0.96), and a higher risk of major bleeding (1.44, 1.21-1.70). The DOAC group was associated with a lower risk of net clinical outcome compared to non-OAC group (0.93, 0.88-0.98). Conclusion In very elderly, high-bleeding risk patients with AF, DOACs which were prescribed in usual clinical practice showed better effectiveness and positive net clinical benefit compared to no OAC treatment.