Real‐World Edoxaban Concentrations in Older Patients Receiving Reduced‐Dose Regimens

This study investigated real‐world edoxaban concentrations across different dosing regimens, with a specific focus on patients who met the inclusion criteria of low‐dose edoxaban for the Elder Care Atrial Fibrillation (ELDERCARE‐AF) trial. Patients with atrial fibrillation receiving edoxaban were enrolled to measure trough concentrations. The levels were compared with the expected therapeutic range (12–43 ng/mL) to define low or high concentrations. Data on ischemic stroke and systemic thromboembolism (SSE), and major bleeding, were collected prospectively. In total, 402 patients (77.2 ± 10.6 years; 52.2% men) were included. The SSE incidence was 1.22 (0.56–2.31) per 100 person years and was significantly associated with low edoxaban concentration (aHR, 4.13 [1.08–15.82]). Among patients meeting the ELDERCARE‐AF criteria ( n = 160), the use of the 15‐mg regimen (ELDER‐15 mg, n = 46) vs. the 30‐mg regimen (ELDER‐30 mg, n = 114) (aOR, 7.65 [2.92–20.09]), higher creatinine clearance (CrCL) (aOR, 1.05 [1.01–1.08]) and lower CHA 2 DS 2 ‐VA score (aOR, 0.69 [0.51, 0.95]) were significantly associated with low concentrations. In the ELDER‐15 mg group, patients with CrCL > 50 mL/min had more than 50% probability of exhibiting low drug concentrations. The incidence of SSE was numerically higher in the ELDER‐15 mg group than the ELDER‐30 mg group (2.34 [0.06–13.02] vs. 1.55 [0.32–4.52]), while major bleeding rates were similar (4.67 [0.57–16.89] vs. 5.15 [2.47–9.48]). In conclusion, low edoxaban concentrations have been associated with thromboembolic events. Among ELDERCARE‐AF‐eligible patients, the 15‐mg regimen results in underexposure to edoxaban, particularly when the CrCL exceeded 50 mL/min.