Background: Though effective and safe, treatment with direct oral anticoagulants (DOAC) in atrial fibrillation (AF) is still associated with thrombotic complications. Whether the measurement of DOAC levels may improve the efficacy of treatment is an open issue. Methods: We carried out the observational, prospective, multicenter study ["Measure and See" Study (MAS) (NCT03803579)]. Blood was collected 15-30 days after starting DOAC treatment in AF patients, who were then followed for one year. Plasma samples were centralized, for DOAC levels measurement. Patients' DOAC levels were converted into drug/dosage standardized values to allow a pooled analysis in a time-dependent, competitive-risk model. The measured values were transformed into standardized values by subtracting from the original values the overall mean value of each DOAC and divided by the standard deviation. Standardized values represent the distance of each value from the overall mean. Results: Trough and peak DOAC levels were assessed in 1657 and 1303 patients, respectively. Twenty-one thrombotic complications were recorded during 1606 years of follow-up (incidence of 1.31% patient/years). 17/21 thrombotic events occurred in patients whose standardized activity levels were below the mean of each DOAC (zero); the incidence was the highest (4.08% patient/years) in patients whose standardized values were in the lowest class (below zero, ≤ -1.00). Conclusions: Early measurement of DOAC levels in AF patients allowed us to identify most of the subjects who, having low baseline DOAC levels, subsequently developed thrombotic complications. Further studies are warranted to assess whether thrombotic complications may be reduced by measuring baseline DOAC levels and modifying treatment when indicated.

The authors have declared no competing interest.

NCT03803579

The study was promoted and funded by the ?Arianna Anticoagulazione? Foundation, which has received an unrestricted grant from the Fondazione ?Cassa di Risparmio in Bologna? to support the study. Becton-Dickinson (Franklin Lakes, NJ, USA) provided test tubes for blood sampling, and Diagnostica Stago (Asnieres-sur-Seine, France) provided reagents to perform DOAC.

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The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Independent review board approval was obtained before all study-related activity from the Ethics Committee (EC) of the coordination center (Cremona) (approval number 14725; 02/05/2018) and from the ECs of all other centers. Written informed consent was obtained from each patient before enrolment. The study promoter provided measures to safeguard the subject's privacy and the protection of personal data according to the EU GDPR 2016/679 and Italian law.

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