Thrombotic events associated with low baseline direct oral anticoagulant levels in atrial fibrillations. the MAS study

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 treatment efficacy is an open issue. We carried out the observational, prospective, multicenter study [MAS Study (NCT03803579)]. Blood was collected 15-30 days after starting DOAC treatment in AF patients who were followed for one year. Plasma samples were centralized for DOAC level 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 (representing the distance of each value from the overall mean) by subtracting the DOAC-specific mean value from the original values and dividing by the standard deviation. 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 (4.82% patient/years) in patients whose standardized values were in the lowest class (below zero,  -1.00). 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.