Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial

Abstract

Aims Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. Methods and results The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02–1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). Conclusion Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.

Activated Clotting Time Monitoring during Atrial Fibrillation Catheter Ablation: Does the Anticoagulant Matter?

“…And more UFH was required when the time from the last dabigatran dose to septal puncture increased, since ACT strongly correlates with dabigatran concentration. In contrast, in the VENTURE-AF, the AXAFA-AFNET 5 and more recently, the ELIMINATE-AF trials, a significantly higher dose of UFH was required to achieve ACT > 300 s among rivaroxaban, apixaban and edoxaban-treated patients respectively compared to VKA-treated patients [6,8,9]. Together these results combined with our data, demonstrate that the effect of UFH on ACT prolongation is dramatically altered by the anticoagulant on board.…”

“…For patients receiving non-VKA oral anticoagulant (DOAC), anticoagulation management has been extrapolated from VKA experience, without additional specific evidence. Recent open-labelled randomized controlled trials (RCTs) performed in patients with uninterrupted DOAC treatment reported a similar incidence of thromboembolism and bleeding events as for VKA [6][7][8][9]. However, until now, few studies have specifically addressed intra-procedural anticoagulation management.…”

“…However, until now, few studies have specifically addressed intra-procedural anticoagulation management. They have all uniformly reported that an unexplained greater amount of UFH was required to achieve a similar ACT target in patients with uninterrupted DOAC, compared to patients receiving VKA [6,[8][9][10][11][12]. The management of these procedures cannot safely be resolved without addressing this simple question: can we transpose intra-procedural anticoagulation strategy from VKA to DOACs?…”

Life-threatening pericardial bleed complicating atrial fibrillation ablation associated with edoxaban therapy successfully managed with prothrombin complex concentrate

“…Oncedaily administered direct oral anticoagulants (DOACs) such as edoxaban can be safely continued uninterrupted at the time of AF ablation. 2 However, management of bleeding complications in the context of DOAC therapy remains a challenge, especially as anti-factor Xa DOACs do not currently have licensed specific reversal agents. Dabigatran, a direct thrombin inhibitor, can be reversed using the agent idarucizumab, but reversal agents for other DOACs are still in development.…”

How minimally interrupted direct oral anticoagulants affect intraprocedural anticoagulation during atrial fibrillation ablation? Insights from a Japanese single‐center retrospective study

“…Calkins et al demonstrated the superiority of uninterrupted dabigatran to warfarin regarding major bleeding events in the RE‐CIRCUIT trial . Continuous apixaban and edoxaban therapies were also comparable to uninterrupted warfarin in the AXAFA‐AFNET 5 and ELIMINATE‐AF trials . Although these studies proved the noninferiority or the superiority of uninterrupted direct OACs compared with uninterrupted VKA therapy in terms of feasibility and safety, concerns remain regarding serious bleeding complications because antidotes for factor Xa inhibitors are not still readily available in many countries including Japan.…”