Edoxaban Plasma Levels in Patients with Non-Valvular Atrial Fibrillation: Inter and Intra-Individual Variability, Correlation with Coagulation Screening Test and Renal Function

Background: High inter-individual variability of the anticoagulant plasma levels of the first three direct oral anticoagulants was previously reported. Aims of the present study were to evaluate edoxaban inter and intra-individual variability in patients with non valvular atrial fibrillation and to assess correlation between edoxaban plasma levels and coagulation screening test and renal function. Methods: From January 31st 2017 to June 30th 2018, a total of 101 NVAF patients were enrolled: 48 patients were on edoxaban 60 mg and 53 on edoxaban 30 mg, once daily. Blood samples were taken at C-trough and at C-peak within the first month (15-25 days) of treatment and then at C-trough each three months. Prothrombin time (PT), activated partial thromboplastin time (aPTT), specific anti-FXa chromogenic test were performed. Creatinine clearance (CrCl) was calculated using the Cockcroft-Gault formula. Results: Mean inter-individual variability expressed as overall coefficient of variation (CV%) values was lower at C-peak (CV%=49) than at C-trough (CV%=68). Mean CV% intra-individual variability was 26.5. No significant correlation was found between edoxaban plasma levels and CrCl (C-trough r/r(2)=-0.007/0.000; C-peak r/r(2)=0.129/0.017). Correlations (r/r(2)), at C-trough and C-peak, between edoxaban levels and PT and aPTT, were 0.386/0.149-0.922/0.851 and 0.283/0.080-0.567/0.321, respectively. Significant discrepancies between PT or aPTT and edoxaban levels were found. Conclusions: This study confirms also for edoxaban a high inter-individual variability in NVAF patients. PT and aPTT are not useful to measure this drug. As for the other two anti-FXa drugs, the absence of a significant correlation between CrCl and edoxaban plasma levels was observed.