Does peak plasma concentration-guided off-label under-dosing of rivaroxaban or apixaban prevent bleeding without increasing thromboembolic events in patients with non-valvular atrial fibrillation?
Anticoagulation monitoring using peak plasma concentration can identify patients with non-valvular atrial fibrillation who may safely benefit from off-label under-dosing of rivaroxaban or apixaban to prevent bleeding.
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.
Suwa et al. (2019) studied this question.
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