Edoxaban joins league with other NOACs as option during AF ablation
Use of uninterrupted edoxaban during catheter ablation for atrial fibrillation (AF) shows comparable safety and efficacy as uninterrupted vitamin K antagonists (VKAs), according to the ELIMINATE-AF trial presented at EHRA 2019.
“Periprocedural stroke or transient ischaemic attack and serious bleeding events represent the most feared complications of AF ablation,” said Dr Stefan Hohnloser from Johann Wolfgang Goethe University in Frankfurt, Germany
“Uninterrupted anticoagulation with VKA helps to minimize the risk for these complications, as does NOAC therapy with rivaroxaban, dabigatran, or apixaban [in later studies],” he added. The current trial provides further evidence on another NOAC, edoxaban in this setting.
The multicentre, phase IIIb ELIMINATE-AF trial with a PROBE* design randomized 560 patients (median age 60.5 years, 71.5 percent male) with AF who were undergoing catheter ablation 2:1 to receive once-daily edoxaban 60 mg (or 30 mg for whom dose reduction was indicated) or a VKA to a goal of INR** 2.0–3.0, for at least 21 days. [EHRA 2019, session LB trials 3]
The primary composite outcome of stroke, ISTH*** major bleeding, or stroke during the postablation period was 0.3 percent in edoxaban-treated patients compared with 2.0 percent in those receiving VKA (hazard ratio [HR], 0.16, 95 percent confidence interval [CI], 0.02–1.73) in the per-protocol analysis.
For the peri- and postprocedural periods, the rate of the composite endpoint was 1.3 percent in the edoxaban arm vs 3.0 percent in the VKA arm (HR, 0.42; p=0.26) in the per-protocol analysis. The results for the modified intention-to-treat analysis (mITT), which included only patients who actually underwent ablation, similarly showed no significant difference between the two arms (2.7 percent and 1.7 percent, HR, 1.60, 95 percent CI, 0.443–5.784).
With regard to safety, major bleeding by ISTH definition occurred in 2.5 percent of patients treated with edoxaban vs 1.5 percent of those on VKA in the mITT population during the overall period, with no statistically significant difference between groups (HR, 1.68, 95 percent CI, 0.463–6.067).
“There were one ischaemic and one haemorrhagic stroke, and both occurred in patients assigned to edoxaban,” noted Hohnloser. No deaths occurred during the study. The incidence of cardiac tamponade was rare and similar in the edoxaban and in the VKA group (0.7 percent vs 1.0 percent), according to Hohnloser.
“ELIMINATE-AF demonstrates that uninterrupted edoxaban treatment represents an alternative to continuous anticoagulation with VKA in patients undergoing catheter ablation of AF,” he concluded.
However, the study was not powered to formally test superiority or noninferiority of edoxaban over VKA, and should be considered exploratory, said Hohnloser. “Such a trial would have needed 3000 to 4000 patients and was thus deemed not to be affordable,” he added.
Reviewing data in perspective
Striking a balance between thromboembolism and bleeding risk can be challenging as catheter ablation is associated with a transient prothrombotic state during and after the procedure, while periprocedural anticoagulation is associated with increased bleeding risk, explained invited discussant Dr Tatjana Potpara of Belgrade University in Belgrade, Serbia.
Reviewing previous data from studies on other NOACs vs warfarin/VKA, the rates of major bleeding events and composite outcomes were “"reassuringly low” across the four trials, she commented.
She also noted that all the trials were insufficiently powered for any meaningful statistical comparisons to be inferred between NOACs and VKAs, and hence should be treated as “exploratory”.
Nonetheless, she acknowledged that these trials demonstrated the feasibility of using uninterrupted NOACs in the setting of AF ablation “at least in relatively young [and] low-to-moderate-stroke-risk patients”, but advised clinicians to fully understand the specific criteria and conditions they were used in the respective trials.
On whether there should be a change in clinical practice regarding switching from one OAC to another in anticipation for catheter ablation, Potpara cautioned that “there is no solid evidence to guide such practice.”