The daily practice of direct oral anticoagulant use in patients with atrial fibrillation; an observational cohort study

Abstract

Background Direct oral anticoagulants (DOACs) are administered in fixed doses without monitoring. There is still little published data on the impact of the absence of monitoring on adherence to medication and stability of DOAC plasma levels over time. Objectives To explore adherence and stability of DOAC plasma levels over time in patients with atrial fibrillation (NVAF) recently started on DOAC therapy. Patients and methods A prospective observational cohort study with structured follow up including assessment of adherence to medication, plasma levels at baseline, 3,6 and 12 months and adverse events. Results We included 164 patients; 89% were previous users of a vitamin K antagonist (VKA). One-year adherence was reasonably good: Morisky adherence measurement scores of 6–8 in 92%. The majority of DOAC plasma levels were within reported on-therapy ranges; dabigatran (median 104.4 ng/ml, IQR 110.2), rivaroxaban (median 185.2 ng/ml, IQR 216.1) and on average levels were not different for full and adjusted doses. There was significant variation between patients, but no significant differences over time within individuals. A substantial proportion of patients starting in the upper-or lower 20 th percentiles remained there during the entire follow up. Seventeen bleedings (16 minor, 1 major) were reported, no ischemic events and bleeding or thrombotic events were not associated with DOAC plasma levels. Conclusions Adherence was reasonably good in the majority of patients. Our data confirm the stability of DOAC plasma levels over time. Knowledge of such data may, in the individual patient, contribute to optimal drug and dose selection.

Self‐reported therapy adherence and predictors for nonadherence in patients who switched from vitamin K antagonists to direct oral anticoagulants

“…Second, our study specifically focused on patients who switched from a VKA to a DOAC, whereas in other observational studies only oral anticoagulant (OAC)‐naïve patients or a combination of OAC‐naïve and OAC‐experienced patients were included. We also found a high anticoagulant adherence rate among VKA‐experienced patients in the SFK database, which was also described in other studies . This might be caused by a higher awareness of the importance of therapy adherence in patients with a history of anticoagulant monitoring.…”

Association of conflicting information from healthcare providers and poor shared decision making with suboptimal adherence in direct oral anticoagulant treatment: A cross-sectional study in patients with atrial fibrillation

“…Monitoring the anticoagulant activity of DOACs is not standard of care and is not likely to become so due to several shortcomings and barriers associated with the various assays [3][4][5]. Dose adjustments are made for DOAC users with reduced creatinine clearance (CrCl), increased age, low weight or other risk factors for bleeding [6]. However, one should be aware that the combination of the shorter half-life of the DOACs with the reduced need and possibility for monitoring implies that their effectiveness is very dependent on strict adherence [7].…”

Plasma Rivaroxaban Level to Identify Patients at Risk of Drug Overexposure: Is a Single Measurement of Drug Level Reliable?

“…[8][9][10][11][12] Our findings are, however, consistent with those of Gulpen and colleagues who explored the intrapatient variability in postdose rivaroxaban level over 1 year using a similar approach to ours. 13 Like us, they showed that a high proportion ($60%) of patients with an initial level that fell in the upper quintile subsequently had levels that were no longer high, but there were also some who had persistently high levels. Gulpen and colleagues concluded that their finding of a significant proportion of patients with persistently high or low drug levels offers the opportunity to adjust doses or switch to a different DOAC to enhance safety and efficacy of DOAC treatment.…”

“…Gulpen and colleagues concluded that their finding of a significant proportion of patients with persistently high or low drug levels offers the opportunity to adjust doses or switch to a different DOAC to enhance safety and efficacy of DOAC treatment. 13 However, identification of patients potentially suitable for dose adjustment would require serial measurement of blood levels and before being accepted the efficacy and safety of such an approach would have to be demonstrated in a randomized trial.…”