biostudies-literatureUnknown124(9)Yamashita T<h4>Background</h4> 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.<h4>Methods</h4> 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.<h4>Results</h4> 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 (<i>n</i> = 427) and 93.3 ± 57.8 ng/mL (<i>n</i> = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 (<i>n</i> = 79; 12.4 ± 12.1 and <i>n</i> = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group (<i>n</i> = 83; 25.1 ± 36.6 and <i>n</i> = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study (<i>n</i> = 39; 18.4 ± 11.2 and <i>n</i> = 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.<h4>Conclusion</h4> 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.Thrombosis and haemostasis874-882https://www.ebi.ac.uk/biostudies/studies/S-EPMC11349424biostudies-literaturePharmacokinetics of Edoxaban 15 mg in Very Elderly Patients with Nonvalvular Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Study.PMC11349424Hennig SOkumura KYamashita TFukuzawa MHayashi TIgawa YfalsePharmacokinetics of Edoxaban 15 mg in Very Elderly Patients with Nonvalvular Atrial Fibrillation: A Subanalysis of the ELDERCARE-AF Study.<h4>Background</h4> 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.<h4>Methods</h4> 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.<h4>Results</h4> 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 (<i>n</i> = 427) and 93.3 ± 57.8 ng/mL (<i>n</i> = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 (<i>n</i> = 79; 12.4 ± 12.1 and <i>n</i> = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group (<i>n</i> = 83; 25.1 ± 36.6 and <i>n</i> = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study (<i>n</i> = 39; 18.4 ± 11.2 and <i>n</i> = 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.<h4>Conclusion</h4> 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.2024-01-01T00:00:00Z2024 Sep2024-11-20T06:15:07.697Z2024-11-20T06:15:07.697ZS-EPMC113494243864133510.1055/s-0044-1785511