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 CHA2DS2-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.
https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1002/cpt.70129
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