Uninterrupted treatment with NOAC as alternative to VKA for ablation of AF
Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trialLiterature - Hohnloser SH, Camm J, Cappato R et al. - Eur Heart J 2019: doi:10.1093/eurheartj/ehz190
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.
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).
This study demonstrated that uninterrupted treatment with edoxaban represents an alternative to continuous VKA during and after catheter ablation in patients with AF. However, a limitation of the study is that it was exploratory and not powered to formally test superiority or noninferiority of edoxaban vs VKA.