WASHINGTON, DC — Patients who underwent ablation for atrial fibrillation had a lower incidence of major bleeding events if they received uninterrupted anticoagulation with the novel oral antagonist (NOAC) dabigatran (Praxada, Boehringer Ingelheim) than with warfarin—in what was called the first large randomized trial to compare these two strategies.
More than 600 patients were randomized and received dabigatran or warfarin starting 4 to 8 weeks before undergoing ablation until 8 weeks later, in the Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy (RE-CIRCUIT) trial.
Major bleeding occurred in five patients (1.6%) in the dabigatran group vs 22 patients (6.9%) in the warfarin group (P<0.001).
Dr Hugh Calkins (Johns Hopkins Medical Institutions, Baltimore, MD) presented what he and others called a "practice-changing" study in a late-breaking clinical-trial session and a later press conference at the American College of Cardiology (ACC) 2017 Scientific Sessions. The study was simultaneously published online in the New England Journal of Medicine.
"I think [this study] will definitely affect my practice, and I think it will affect the practice of electrophysiologists around the world," he said. Another advantage of dabigatran is that if major uncontrollable bleeding occurs, "it's really reassuring" to know that the reversal agent idarucizumab (Praxbind, Boehringer Ingelheim) is "on the shelf," although it was not used in the current study.
The trial "will certainly impact clinical practice," echoed the assigned discussant at the press conference, Dr Jagmeet Singh (Harvard Medical School, Boston), "because now you have a periprocedural strategy that is associated with minimal bleeding complications and you also have a reversal agent at hand."
Three other experts who spoke to heartwire from Medscape agreed and speculated this trial might change their clinical practices.
"Our practice has been to do afib ablation largely on warfarin or one of the Xa inhibitors," rivaroxaban (Xarelto, Bayer/Janssen Pharmaceuticals), apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), or edoxaban (Savaysa/Lixiana, Daiichi Sankyo), session panelist Dr William G Stevenson (Harvard University, Boston, MA) told heartwire . "We had been switching people off dabigatran because of the lack of data and concern [about strokes]. We will likely no longer switch them off dabigatran; we'll discuss it with our group, and we look forward to reading the paper."
"I think it will change practice," session panelist Dr Kenneth A Ellenbogen (VCU School of Medicine, Richmond) agreed. "People will say it's safer to be on a NOAC when you are having afib ablation than on warfarin. Period."
"We get patients referred to us by physicians who have already put their patients on an anticoagulant if they have afib; so generally we just continue with what they have," press conference moderator Dr John Fisher (Albert Einstein College of Medicine; New York City) told heartwire . "If we are seeing a patient fresh and we think that we are going to schedule the patient for ablation, the considerations that we heard today are important."
Can Patients Slated for AF Ablation Continue or Start Dabigatran?
Catheter ablation of AF is typically performed with uninterrupted anticoagulation with warfarin or interrupted anticoagulation with a NOAC, but it is cumbersome to transition patients to warfarin prior to ablation, Calkins said.
The major concern with an uninterrupted NOAC is the risk of a life-threatening bleed. But the VENTURE-AF clinical trial, which randomized 248 patients undergoing catheter ablation for AF to receive uninterrupted rivaroxaban or uninterrupted warfarin suggested that uninterrupted anticoagulation with a NOAC was feasible.
RE-CIRCUIT aimed to investigate the safety and efficacy of uninterrupted dabigatran vs uninterrupted warfarin in such patients.
Between April 2015 and July 2016, the trial randomized 678 patients who were scheduled for catheter ablation for paroxysmal or persistent AF at 104 sites in 11 countries.
A total of 317 patients on dabigatran (150 mg twice daily) and 318 patients on warfarin (with a target INR of 2.0 or 3.0) underwent ablation.
Patients in both groups had similar baseline characteristics. They had a mean age of 59; most (68%) had paroxysmal AF; and they had a mean CHA2DS2-VASc score of 2. Over a quarter of the patients were receiving a NOAC: dabigatran (12%), rivaroxaban (9%), apixaban (7%), or edoxaban (<1%).
During the study, patients in the warfarin group were in the therapeutic INR range 66% of the time.
Patients on uninterrupted dabigatran had significantly fewer major bleeding events than patients on uninterrupted warfarin (relative risk reduction 77.2%).
The five patients in the dabigatran group with a major bleeding event had pericardial tamponade (one patient), pericardial effusion (one), groin bleed (two), and gastrointestinal (GI) bleed (one).
The 23 patients in the warfarin group with a major bleeding event had pericardial tamponade (six), groin bleed (two), groin hematoma (eight), GI bleed (two), intracranial bleed (two), pseudoaneurysm (one), and hematoma (two).
About 18% of patients in each group had minor bleeding events. None of the patients had a stroke and one patient on warfarin had a transient ischemic attack (TIA). No patient died.
Dabigatran Concerns Refuted, Trials of Other NOACs Ongoing
"This is something that we have been struggling with since concern was raised that dabigatran might be associated with more thromboembolic events, and this clearly refutes that concern," Stevenson said.
"The main takeaway is that dabigatran kept without any interruption is safe and can and maybe should be used during AF ablations," according to Fisher.
"I think it'll be interesting to see how this pans out in a head-to-head trial" with other direct oral anticoagulants (DOACs) in the future, Singh mused.
"A stroke is a terrible thing during an AF ablation procedure and a cardiac tamponade is the most common cause of death from the procedure, so now we have high-quality data showing that if you perform this procedure on uninterrupted dabigatran the risk of stroke is extremely low," Calkins said.
"And the logistics of warfarin are a pain" when patients show up with an INR that is too high or too low, he added.
"So for many reasons I think this is a far better strategy, and having an antidote that you can give to completely shut it down in the case of really uncontrolled bleeding—to me and to any patient . . . would be very reassuring and . . . will really support this approach."
Warfarin is "extremely fussy" because patients have to watch their diet and it is "par for the course" that only 66% of patients on warfarin were within the therapeutic range in this study, even though they were closely followed, according to Fisher. "That's another reason to favor the NOACs, because we at least think that you get a steady dose, although actually nobody knows because they are not tested."
"Clearly there were all sorts of prior studies that suggested that dabigatran was associated with a high risk of stroke, a high risk of systemic embolism, and a high risk of bleeding," Ellenbogen told heartwire .
"I think this is what happens when you do a prospective randomized trial; you sweep out the cobwebs out of the closet. I think that it shows that it's safer than warfarin.
"There are multiple other [NOAC] trials that are going to come out over the next year all looking at this," he noted.
"My personal bias is that the NOACs are safer than warfarin and the only reason every patient is not taking a NOAC . . . or 95% of them are not, is because of cost. If NOACs were as cheap as warfarin (which is $4 a month in some drugstores), then everyone would be on them."
There is no need for blood testing; there are fewer interactions, "and now we see that there's some studies that suggest that they're safer than warfarin, in the setting of an afib ablation. That's pretty impressive."
The study was funded by Boehringer Ingelheim. Calkins reports receiving lecture fees/honoraria from Boehringer Ingelheim and Medtronic and consulting for Medtronic, Abbott Medical, and AtriCure. Disclosures for the coauthors are listed on the journal website. Singh reports receiving consultant fees/honoraria from Biotronik, Boston Scientific, Liva Nova, Medtronic, and St Jude Medical; being on the data safety monitoring board for Respicardia; and receiving research grants from Boston Scientific and St Jude Medical. Ellenbogen reports receiving consultant fees/honoraria from the American Heart Association, AtriCure, Biosense Webster, Biotronik, Boston Science, the Heart Rhythm Society, Janssen, Medtronic, Pfizer, Sentra Heart, and St Jude Medical; being on the data safety monitoring board of and having given expert witness testimony for Medtronic; and receiving research grants from AtriCure, Daiichi Sankyo, Medtronic, Boston Science, Biosense Webster, and the National Institutes of Health. Stevenson reports receiving consultant fees/honoraria from St Jude Medical and having a patent for needle ablation. Fisher reports receiving consultant fees/honoraria from Medtronic and has other ties to Biotronik, Boston Scientific/GDT, Medtronic, and St Jude Medical.
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Heartwire from Medscape © 2017
Cite this: Fewer Major Bleeds on Uninterrupted Dabigatran in AF Ablation vs Warfarin: RE-CIRCUIT - Medscape - Mar 28, 2017.