A proposal for dose‐adjustment of dabigatran etexilate in atrial fibrillation guided by thrombin time

Abstract

Dabigatran is an oral anticoagulant that is increasingly used for atrial fibrillation (AF). Presently, many authorities state that routine laboratory coagulation monitoring is not required. However, data have recently been published demonstrating that higher trough plasma dabigatran concentrations are associated with lower thromboembolic and higher haemorrhagic event rates. Using these data, we simulate a range of AF patients with varying risks for these events and derive a target range of trough plasma dabigatran concentrations (30-130 μg l −1). Finally, we propose that a conventional screening coagulation assay, the thrombin time (TT), can be used to discern whether or not patients are within this range of dabigatran concentrations.

Enhanced Elimination of Dabigatran Through Extracorporeal Methods

“…The mean dabigatran trough concentration in the RE-LY study was 91 ng/mL (28.2-155 ng/mL, 10th and 90th percentile) [36]. However, a therapeutic range of 30 to 130 ng/mL at trough has been suggested [46]. Levels above 200 ng/mL at trough are associated with an increase in bleeding [52].…”

“…The utility of coagulation assays for assessing the effects of dabigatran has been discussed in detail previously [25,45,46]. The activated partial thromboplastin time (aPTT) and thrombin time (TT) assays are useful for qualitative effect of dabigatran.…”

Non‐vitamin K Oral Anticoagulants Versus Warfarin for Patients with Atrial Fibrillation: Absolute Benefit and Harm Assessments Yield Novel Insights

“…This characteristic may be particularly relevant to the suspected pharmacokinetic heterogeneity of dabigatran (or more strictly its prodrug dabigatran etexilate; Dabigatran bioavailability is also augmented by increased gastric acidity and chewing the capsule .) which has been mired in controversy owing to suggestions that in selected patients its benefit risk ratio might be improved by some sort of therapeutic monitoring . The resulting quandary appears consistent with its very limited oral bioavailability of about 6‐7% compared to about 50% or more for the other NOACs.…”

“…This was because the relevant individual trials did not distinguish between different types of intracranial bleeds (traumatic vs. stroke), entailed far fewer patients than the AF trials, and did not exclude patients with AF, and treatment durations were generally much shorter (3-12 months) and variably documented. Table 1 shows that astonishingly, among NOAC-treated patients enduring a primary outcome in ARISTOTLE, RE-LY, ENGAGE, and ROCKET AF, respective hemorrhagic stroke rates were down to 19,9,17, and 15% compared to 29, 23, 27, and 21% for patients taking warfarin. While such encouraging results with NAOCs could well be due to inherently lower hemorrhagic stroke risks despite superior clot prevention efficacy, they could also be a reflection of fewer embolic strokes and a consequential reduction in instances of hemorrhagic transformation of the resulting infarcts.…”

Screening coagulation tests are underutilised in patients on dabigatran presenting with thromboembolic or haemorrhagic events

“…These positively correlate with the plasma concentrations of dabigatran, a non‐vitamin K antagonist oral anticoagulant . There is an increasing recognition that coagulation tests may be useful in the management of patients on dabigatran presenting with thromboembolic/haemorrhagic events …”