Rivaroxaban or Apixaban for Non-Valvular Atrial Fibrillation　― Efficacy and Safety of Off-Label Under-Dosing According to Plasma Concentration ―

Abstract

Background: Practice-based investigations on direct oral anticoagulant (DOAC) treatment for non-valvular atrial fibrillation (NVAF) have shown that off-label under-dosing is increasingly becoming an issue. Here, we investigate the significance of drug monitoring to prevent undesirable under-dosing with DOAC.

Methods and Results: In 255 outpatients with NVAF undergoing treatment with rivaroxaban or apixaban we estimated the cut-offs for bleeding events using drug plasma concentration (PC) data 3 h after drug treatment, that is, at the peak level. Furthermore, we evaluated the appropriateness of labeled and off-label dosing implemented for 348 patients using the obtainable PC threshold. A total of 73 off-label under-dose users of rivaroxaban (37% of all users and 63% of lower dose users) had acceptable peak PC (155–400 ng/mL). Additionally, 46 off-label under-dose users of apixaban (31% of all users and 55% of lower dose users) received appropriate doses according to peak PC threshold (90−386.4 ng/mL). These off-label under-dose users reported no bleeding or thromboembolic events during follow-up.

Conclusions: Anticoagulation monitoring enables personalized and appropriate off-label under-dosing in NVAF patients on rivaroxaban or apixaban through the measurement of peak PC during DOAC use.