Low Levels of Direct Oral Anticoagulants at Steady State in Atrial Fibrillation Patients Who Later Develop Thrombotic Complications; The Prospective Mas (Measure and See) Study

Abstract

BackgroundThough 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.MethodsWe 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.ResultsTrough 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, σ; - 1.00).ConclusionsEarly 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.

How the Hemostasis Laboratory can Help Clinicians to Manage Patients on Oral Anticoagulants

“…In fact, some of the patients who had relatively low DOAC levels showed a greater propensity to develop thrombotic relapses more frequently during follow-up. 12 …”