Running after Activated Clotting Time Values in Patients Receiving Direct Oral Anticoagulants: A Potentially Dangerous Race. Results from a Prospective Study in Atrial Fibrillation Catheter Ablation Procedures

Abstract

Background: Activated Clotting Time (ACT) guided heparinization is the gold standard for titrating unfractionated heparin (UFH) administration during atrial fibrillation (AF) ablation procedures. The current ACT target (300 s) is based on studies in patients receiving a vitamin K antagonist (VKA). Several studies have shown that in patients receiving Direct Oral Anticoagulants (DOACs), the correlation between ACT values and UFH delivered dose is weak. Objective: To assess the relationship between ACT and real heparin anticoagulant effect measured by anti-Xa activity in patients receiving different anticoagulant treatments. Methods: Patients referred for AF catheter ablation in our centre were prospectively included depending on their anticoagulant type. Results: 113 patients were included, receiving rivaroxaban (n = 30), apixaban (n = 30), dabigatran (n = 30), and VKA (n = 23). To meet target ACT, a higher UFH dose was required in DOAC than VKA patients (14,077.8 IU vs. 9565.2 IU, p < 0.001), leading to a longer time to achieve target ACT (46.5 min vs. 27.3 min, p = 0.001). The correlation of ACT and anti-Xa activity was tighter in the VKA group (Spearman correlation ρ = 0.53), compared to the DOAC group (ρ = 0.19). Despite lower ACT values in the DOAC group, this group demonstrated a higher mean anti-Xa activity compared to the VKA group (1.56 ± 0.39 vs. 1.14 ± 0.36; p = 0.002). Conclusion: Use of a conventional ACT threshold at 300 s during AF ablation procedures leads to a significant increase in UFH administration in patients treated with DOACs. This increase corresponds more likely to an overdosing than a real increase in UFH requirement.

Study of Modifications Induced by Continued Direct Oral Anticoagulant Therapy during Atrial Fibrillation Ablation Procedures on Standard Hemostasis Parameters

“…Others studies also concluded that a higher dose of UFH is required to achieve an ACT > 300 s in patients treated with DOAC, with a greater dose in patients treated with rivaroxaban and apixaban as compared to dabigatran [ 8 , 10 , 21 , 27 , 32 , 33 , 34 ]. In our study, the increase in ACT during the procedure correlated with the increase in anti-Xa activity of UFH, which is in line with the study from Benali et al, where ACT and anti-Xa activity not only correlated well in patients treated with VKAs, but also with DOACs, although this association was weaker [ 33 ]. Thus, ACT appears to be able to appropriately detect heparin boluses, but with a different response among DOACs.…”

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

“…Some authors suggested that the higher doses of UFH administered to patients on DOACs, compared with patients on VKAs, could be detrimental by adding to the residual effect of uninterrupted DOACs, putting patients at increased bleeding risk ( 21 , 28 ). However, meta-analyses of randomized trials and observational studies comparing uninterrupted VKA and DOAC treatment approaches are reassuring, identifying no increase in bleeding risk with DOACs compared with VKAs ( 80 , 81 ); dabigatran was even safer than VKAs in the RE-CIRCUIT randomized trial [absolute risk difference −5.3% (95% confidence interval: −8.4 to −2.2%), p < 0.001] ( 10 ).…”

“…This threshold is applied similarly for CAAF on DOAC therapy despite a lower level of evidence. However, higher UFH doses are required to achieve the ACT goal of 300 s when DOACs are on board, compared to VKAs ( 8 , 15 , 18 , 21 – 27 ), which corresponds to a potential overdosage according to some authors ( 21 , 28 ). Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during the procedure and that considering the residual effect of DOACs would not be as important as expected.…”

Emergency Cardiac Surgery in Patients on Direct Oral Anticoagulants

“…One more thing to consider while managing anticoagulation during cardiopulmonary bypass is the fact that DOACs may interfere with activated clotting time (ACT) giving falsely low values that do not reflect actual anticoagulation ( 11 ).…”