Pharmacokinetics of Edoxaban 15 mg in Very Elderly Patients with Nonvalvular Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Study.

Background:  We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk.

Methods:  This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies.

Results:  The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 ( = 427) and 93.3 ± 57.8 ng/mL ( = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 ( = 79; 12.4 ± 12.1 and  = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group ( = 83; 25.1 ± 36.6 and  = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study ( = 39; 18.4 ± 11.2 and  = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not.

Conclusion:  PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight.