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.

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