麻豆传媒

CHICAGO -- A brief interruption in apixaban (Eliquis) appears as safe as continuing it for patients about to undergo atrial fibrillation ablation, with no difference in outcomes for either versus historical warfarin use, the AEIOU (Apixaban Evaluation Of Interrupted Or Uninterrupted Anticoagulation For Ablation Of Atrial Fibrillation) trial showed.

Clinically-significant bleeding events in the first 30 days with a Bleeding Academic Research Consortium (BARC) score of 2 or greater occurred in 11.3% of uninterrupted apixaban patients, 9.7% who got apixaban with the morning dose held before ablation, and 9.8% of a retrospective warfarin treated patients at the same centers, none of which differed significantly.

Major bleeding events (BARC≥3) occurred in 1.3%, 2.1%, and 1.4% of these groups, respectively, again without statistically significant difference among the arms, Matthew Reynolds, MD, of Lahey Hospital and Medical Center in Burlington, Mass., reported here at the Heart Rhythm Society meeting.

Ischemic events were uncommon across treatment arms, with a 0.7% rate of transient ischemic attack (TIA) in each based on one to two events in each arm. No ischemic strokes, systemic embolism, or deaths occurred in any group.

"Really the message here is that major bleeding was low, was less than 2%, no matter how you did it," Reynolds said at a press briefing for the late-breaking clinical trial session. "That's reassuring. There are still people who for various reasons have a preference for either not holding any doses or maybe just holding one. And we found both of those apixaban strategies appeared to be safe and effective, and certainly compared well with the previous standard of uninterrupted warfarin."

The session's co-chair, Andrew Krahn, MD, of the University of British Columbia in Vancouver, agreed that either strategy is reasonable, although the science doesn't strictly say they are equivalent.

"The good news is it's becoming harder and harder to show a difference between different strategies of approaching this because they all work well at reducing risk of stroke," he said at the press conference. "There's always an art in medicine. 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."

Even so, with this data and that from the RE-CIRCUIT trial showing less bleeding with uninterrupted dabigatran (Pradaxa) than warfarin, "I do think we are going to be moving more and more towards uninterrupted NOAC [non-vitamin K oral anticoagulants] in this group of patients to prevent the difficulties with variable INRs and given the safety that has been shown."

The NOACs all seem to behaving in a similar fashion, Reynolds said. He chalked up the difference between trials -- similarity between arms in AIEOU (which he called hands-down the best trial acronym of the day) versus the superiority of dabigatran in RE-CIRCUIT -- to the high rate of major bleeding in the warfarin arm in RE-CIRCUIT, at 6.9%. "If you look at the literature on this, I think that's an outlier ... They were different studies and they used different scoring systems for major versus minor bleeding, but those systems actually are fairly similar."

"This study supports the concept that in non-valvular atrial fibrillation, apixaban and likely the other NOACs could be used in the same way [uninterrupted]," commented Gordon Tomaselli, MD, of Johns Hopkins. "There are likely to be more studies with the other NOACs that will challenge the notion that dabigatran is the only agent superior to warfarin for uninterrupted anticoagulation at the time of atrial fibrillation ablation."

There was concern over lack of a reversal agent specifically for the factor Xa inhibitors to control bleeding events, but the trial showed a very infrequent need for one, Reynolds said. "Even in the one patient in our study in whom the worst thing happened, which was 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 ... To me, the whole word here is reassurance."

The prospective, multicenter AIEOU trial included 300 patients on apixaban, randomized to get it uninterrupted through the ablation procedure or held for the morning dose on the day of procedure, as well as a matched retrospective cohort of 295 patients who received warfarin uninterrupted at the same centers.

A fully randomized trial comparing apixaban and vitamin K antagonists -- the from Europe – has completed enrollment and results can be expected within the year, Reynolds noted.

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