Uninterrupted treatment with NOAC as alternative to VKA for ablation of AF

Introduction and methods

Before, during and after ablation for atrial fibrillation (AF), patients are treated with systemic anticoagulant therapy to reduce the risk of thromboembolic events [1,2]. Data on continuous peri-procedural use of edoxaban during ablation in patients with AF are lacking. The ELIMINATE-AF trial therefore investigated the efficacy and safety of uninterrupted edoxaban vs. VKA in patients undergoing catheter ablation for AF.

The exploratory ELIMINATE-AF (March 2017 – Sept 2018) was a multinational, multicenter, randomized, open-label, parallel-group, blinded-endpoint evaluation (PROBE) trial including patients aged ≥18 years with documented non-valvular AF scheduled for their first or repeated catheter ablation for AF. Eligible patients were randomized 2:1 to receive either once-daily edoxaban 60 mg (or 30 mg if they met ≥1 criterion for dose reduction) or VKA. Maximum time between the last pre-ablation edoxaban dose and the ablation procedure was 18 hours. During ablation unfractionated heparin was administered. Administration of study drug was reinitiated >6 hours post-sheath removal after achieving adequate hemostasis and continued for 90 days post-ablation. In a sub-study silent cerebral lesions were assessed by performing MRI.

The modified intent-to-treat (mITT) population (n=602) included all randomized patients who received ≥1 dose of study drug. The mITT analysis was used for the primary and key secondary safety parameters. The per-protocol (PP) population (n=417) consisted of patients who received study drug and underwent catheter ablation. PP analysis and post-ablation period was used for the primary outcome parameter and key secondary efficacy parameters.

Primary study endpoint was time to first occurrence of all-cause death, stroke (ischemic, hemorrhagic or undetermined), or ISTH-defined major bleeding during the period from the end of the ablation procedure to the end of treatment (post-ablation period; 90 days). The primary safety endpoint was the time to the first occurrence of ISTH-defined major bleeding from the date of the first administration of study drug to the end of treatment.

Main results

Primary and safety endpoint

• In the PP population post-ablation, the primary endpoint occurred in 0.3% (1 patient) of those who received edoxaban and in 2.0% (2 patients) of those treated with VKA (HR: 0.16, 95%CI: 0.02-1.73), which were all major bleedings.
• In the PP population peri- and post-ablation, the primary endpoint was seen in 1.3% (4 patients) of subjects treated with edoxaban and in 3.0% (3 patients) of those who received VKA (HR: 0.42, 95%CI: 0.10-1.89), and in 2.7% (10 patients) and in 1.7% (3 patients) of individuals in the mITT population peri- and post-ablation, respectively.
• During the total study period, the primary safety endpoint was observed in 2.5% (10 patients) of participants in the edoxaban group vs. in 1.5% (3 patients) of those in the VKA group.
• During the total study period (mITT), one ischemic and one hemorrhagic stroke occurred, both in the edoxaban group (30 and 60 mg, respectively).

MRI-established cerebral microembolism

• Acute cerebral microembolism ≤10 mm size was seen in 13.8% ([7.52-20.07], 16 patients) of subjects assigned to edoxaban and in 9.6% ([1.60-17.63], 5 patients) of those who received VKA (nominal P=0.62).

Conclusion

References

Find this article online at Eur Heart J