Direct-acting oral anticoagulant drug level monitoring in clinical patient management

Abstract

The role of drug-level monitoring among patients using direct-acting oral anticoagulant (DOAC) is unclear. We aimed to investigate its 'real-life' utilization and effect on clinical management. A review of records of patients who underwent DOAC level testing during 2013-2017. Overall, 212 patients (median age 77 years) underwent 292 DOAC measurements [apixaban (n = 147), rivaroxaban (n = 102), dabigatran (n = 43)]. Monitoring volume increased by 460% during study period. DOAC level testing was performed during routine follow-up in 51 (17.5%) cases, whereas the remaining 241 (82.5%) measurements were performed due to selected clinical circumstances, most commonly: bleeding (n = 60), perioperative status (n = 45), breakthrough thrombosis (n = 37) and renal failure (n = 35). Drug levels were within the expected range in 210 (71.9%), above the expected range in 62 (21.2%) and lower than expected range in 20 (6.8%). In multivariate analysis, older age (P = 0.005), lower glomerular filtration rate (P = 0.001) and lower body mass index (P = 0.006) were associated with DOAC levels above the expected range. Clinical decisions were affected by DOAC monitoring following most (140/241, 58.1%) measurements for which we identified an indication for testing; yet only rarely when monitoring was performed during routine follow-up (7.8%, 4/51) (P < 0.0001). While no benefit of routine DOAC monitoring was observed, drug level measurement has an important role in the management of patients in selected circumstances. Age, body weight and creatinine clearance were found to be significant predictors of drug levels. Future studies are warranted to establish associations between drug levels and outcomes, and better delineate the role of DOAC monitoring.

Rivaroxaban Precision Dosing Strategy for Real‐World Atrial Fibrillation Patients

“…This premise is supported by publications suggesting the effect of body weight on drug exposure is minimal and certainly less than the effects seen with CrCl. 17,18 Although there is evidence that either PT or drug concentration feedback-based dosing may have additional advantages, [19][20][21] we have not addressed this potential.…”

“…Rivaroxaban currently does not have a defined therapeutic window, but clinical response depends on exposure. 20,21,27 Other DOACs, such as dabigatran, have more clearly characterized exposure/response relationships, which suggest there may be an optimal plasma drug concentration range. 28,29 The mechanisms behind the exposure/response relationship are likely similar in all DOACs, and higher exposures of rivaroxaban were assumed to increase the risk of bleeding, whereas lower exposures increased the risk of stroke.…”

Progress in the monitoring of direct oral anticoagulant therapy

“…Rottenstreich et al () have shared their experience of DOAC drug level monitoring in clinical patient management. Their aim was to describe the real‐life utilisation of DOAC levels in practice and its effect on clinical management.…”

“…This study however does not report the exact time after dose that the PTs were measured, so it is difficult to know if like is being compared to like (in terms of time after dose) and therefore, it is again difficult to draw any firm conclusions from this. Rottenstreich et al (2018) have shared their experience of DOAC drug level monitoring in clinical patient management. Their aim was to describe the real-life utilisation of DOAC levels in practice and its effect on clinical management.…”

Should we monitor the direct oral anticoagulants?

“…The available DOACs have shown both inter-individual and intra-individual pharmacokinetic variability [1][2][3][4]. Even less predictable drug concentrations have been associated with advanced age, renal insufficiency, and body weight extremes [5][6][7]. All of the approved DOACs are substrates of P-glycoprotein, an important mediator of drug interactions.…”