Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

Abstract

PurposeDabigatran (D) is increasingly used for chronic anticoagulation in place of warfarin (W). These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation.Patients and methodsIn a retrospective study of patients treated with D, W, or neither drug (N) undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM) analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups.ResultsData for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05) to the initial heparin bolus than Group W (approximately 50%). Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the heparin effect in the model did not differ significantly among groups.ConclusionPatients on warfarin with an average INR of 1.5 or higher are more sensitive to heparin than patients not previously anticoagulated or patients who discontinued dabigatran 27 hours earlier (approximately two half-lives) warfarin.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

“…Unfortunately, few data are available regarding this topic. A pharmacokinetic-pharmacodynamic study performed in CAAF patients identified that the response to intravenous UFH was similar between patients on dabigatran and patients without baseline anticoagulation (same ACT increase for a given UFH bolus), but was enhanced in patients on VKAs (increased ACT increase for a given UFH bolus) ( 63 ). However, dabigatran was often skipped for one dose before the procedure, probably resulting in low plasma concentrations, which limits the findings of the study.…”

Periprocedural Management of Novel Oral Anticoagulants During Atrial Fibrillation Ablation: Controversies and Review of the Current Evidence

“…Thus it is unlikely that experience with VKA can be directly applied to the NOACs. Moreover, there is increasing recognition of an interaction between NOACs and UFH [12,13].…”