Plasma levels of direct oral anticoagulants in non-valvular atrial fibrillation patients at the time of acute cardioembolic or bleeding events

Abstract

Abstract Background Direct oral anticoagulants (DOACs) are approved for preventing cardioembolic events in patients with non-valvular atrial fibrillation (NVAF) (1). Unlike Heparin and vitamin K antagonists, DOACs are commonly used without the need for clotting time monitoring, which results in limited data on the correlation between plasma levels and adverse events (2). Objective This study aimed to evaluate, in a real-world cohort of NVAF patients, the relationship between the occurrence of acute cardioembolic or major bleeding events and the plasma levels of DOACs measured at the time of the events. Methods and Results This study included 400 NVAF patients on DOAC therapy from the INSIghT registry who underwent plasma drug level testing at the time of an adverse event (116 cases) or during an elective hospitalization or outpatient visit (284 controls). Out of 116 cases, 74 experienced a cardioembolic event while 42 had a major bleeding. Patients with cardioembolic events presented low (i.e., in the first and second quartiles) DOAC plasma levels (50 vs. 24, p<0.01), while patients with major bleeding events had high (i.e., in the third and fourth quartiles) DOAC plasma levels (25 vs. 14, p<0.01). Conclusions This study highlights the possible association between plasma levels of DOACs and the risk of adverse events, but further research is needed to fully understand the potential benefits DOAC monitoring and individualized dosing.Fig. 1Fig. 2