AEIOU Advances Uninterrupted NOAC Strategy in AF Ablation

Patrice Wendling

May 15, 2017

CHICAGO, IL — New research shows apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), either uninterrupted or interrupted by a single dose, was associated with rates of major and minor bleeding similar to uninterrupted warfarin in patients who underwent ablation for atrial fibrillation[1].

In addition, no strokes and systemic embolism occurred among the three strategies.

Dr Matthew Reynolds

"Really, the message here is that major bleeding was low, was less than 2% no matter how you did it. And I think that's reassuring," study author Dr Matthew Reynolds (Lahey Hospital and Medical center, Burlington, MA) told the press after presenting the Apixaban Evaluation of Interrupted or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation (AEIOU) trial here at the Heart Rhythm Society (HRS) Scientific Sessions 2017.

"There are still people who for their own reasons have a preference for either not holding any doses or maybe just holding one. And we found that both of those apixaban strategies appeared to be safe and effective and certainly compared very well with the previous standard of uninterrupted warfarin," he said.

Earlier this year, the RE-CIRCUIT investigators reported the novel oral anticoagulant (NOAC) dabigatran (Praxada, Boehringer Ingelheim) was superior to warfarin on major bleeding (1.6% vs 6.9%) in AF ablation patients.

That study was described as "practice-changing," but questions remained whether a strategy of uninterrupted anticoagulation would pan out with apixaban, a factor Xa inhibitor that lacks a specific reversal agent to control bleeding.

In the present late-breaking clinical trial, there was little need for such an agent, Reynolds remarked.

"Even in the one patient in our study who had the worst imaginable thing happen, which is they had to have open-heart surgery in the middle of an EP procedure, that patient took a dose of apixaban that morning and still survived," he said. "To me, the whole word here is reassurance."

The primary safety end point of clinically significant bleeding (BARC score >2) occurred in 11.3% of uninterrupted-apixaban patients, 9.7% of those with the morning apixaban dose withheld, and 9.8% of warfarin-treated patients.

Rates of major bleeding (BARC >3) were also not statistically significantly different between groups at 1.3%, 2.1%, and 1.4%, respectively.

One patient in each of the apixaban groups and two in the warfarin group experienced a transient ischemic attack. No deaths occurred.

Dr Andrew Krahn (University of British Columbia, Vancouver) told heartwire from Medscape, "It's becoming harder and harder to show a difference between different strategies of approaching this, because they all work well at reducing the risk of stroke. What patients are terrified of is the risk of stroke that happens in conjunction with the procedure; and we're chipping away at the notion of making zero the norm."

From a robust science perspective, he said the preliminary data don't prove the two apixaban strategies are "equivalent or one is better than other" but that on balance, both are reasonable.

"There's always an art in medicine," Krahn said. "And some of that art is around, for example, the nuance in a person's bleeding or thrombosis risk. I would expect this supports the idea that if in your judgment this is a high-bleeding-risk patient, you will skip a dose or if it is a high­-thrombosis-risk person who has had two TIAs and a previous stroke, we will continue apixaban."

Reynolds suggested that the 6.9% major bleeding rate in the warfarin arm of RE-CIRCUIT was likely "an outlier" based on the literature and said it is not consistent with the 1.4% major bleeding rate observed with uninterrupted warfarin in AEIOU.

That said, in light of data from AEIOU and RE-CIRCUIT, "I do think we are going to be moving more and more toward uninterrupted NOAC anticoagulation in this group of patients to prevent the difficulties with variable INRs and given the safety that is demonstrated in people in your trial and others who have experience using it," commented Dr Thomas Deering (Piedmont Heart Institute, Atlanta, GA), who was not involved in the study.

AEIOU prospectively enrolled 300 patients from 18 US centers and randomly assigned them to apixaban uninterrupted or to the morning apixaban dose withheld the day of catheter ablation. Patients were then matched 1:1 based on age, sex, and AF pattern to a retrospective warfarin cohort of 295 patients treated with uninterrupted warfarin (target INR 2-3; no bridging anticoagulation).

At baseline, patient characteristics were similar between the three groups, save for a significantly higher ejection fraction in the combined apixaban groups than in the warfarin group (mean 56.7% vs 54.7%) and lower body mass index (mean 30.5 vs 32.4 kg/m2).

There were procedural differences between groups. Prior AF ablation, use of transesophageal echo within 48 hours of ablation, and a double-transseptal puncture were significantly more common in the warfarin group, while use of force-sensing radiofrequency, pulmonary vein isolation, and robotic catheter navigation were significantly more common in the apixaban groups.

The study was sponsored by the Baim Institute for Clinical Research with financial support from Bristol-Myers Squibb/Pfizer. Reynolds reports compensation for services to Biosense Webster, Sanofi, Medtronic, and St Jude Medical (now Abbott). Disclosures for the coauthors are listed in the abstract. Krahn reports no relevant financial relationships. Deering disclosed serving as a speaker for Boston Scientific; recently divesting an equity interest in CorMatrix and Zywie; research funding to his institution from CorMatrix, Spectranetics, Sorin Group, Boston Scientific, Medtronic, and St Jude Medical; and other compensation from Medtronic and Boston Scientific.

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