Results from the RE-CIRCUIT study have shown that uninterrupted dabigatran (Pradaxa, Boehringer Ingelheim), was associated with fewer bleeding complications than uninterrupted warfarin before, during and after atrial fibrillation (AF) treatment with ablation.
The findings offer evidence that dabigatran is a safe and effective alternative to warfarin in the context of AF ablation. The trial showed a 5.3% reduction in its primary endpoint, major bleeding events during ablation or in the first two months after the procedure, with major bleeds occurring in 1.6% of study participants who received dabigatran and 6.9% of patients on warfarin.
RE-CIRCUIT (Randomized evaluation of dabigatran etexilate compared to warfarin in pulmonary vein ablation: Assessment of an uninterrupted periprocedural anticoagulation strategy) was presented by Hugh Calkins (Johns Hopkins Hospital, Baltimore, USA) at the 2017 scientific session of the American College of Cardiology (ACC; 17–19 March, Washington, DC, USA) and simultaneously published in The New England Journal of Medicine (NEJM).
“I think it is great news for the field,” said Calkins. “There have been very few randomised studies focused on doing ablation procedures in fully anticoagulated patients, and the use of non-vitamin K antagonist oral anticoagulants (NOACs) has been increasing dramatically. I expect these findings will encourage clinicians to quickly shift to doing this procedure with uninterrupted use of NOACs.”
Previous studies have shown the performance of AF ablation on uninterrupted anticoagulation with a vitamin K antagonist (VKA)—such as warfarin—helps to minimise the risk of thromboembolic and bleeding events, which are major complications of this procedure, commented Calkins. Data on the use of NOACs around the time of catheter ablation are limited. “Most electrophysiologists have interrupted the dose of NOACs before catheter ablation, out of concern that bleeding complications could lead to worse outcomes in the presence of an irreversible anticoagulant. High-risk patients receiving NOACs often had their treatment changed over to VKAs periprocedurally, so that ablation could be performed with continuous anticoagulation, and then were switched back to a NOAC, one or two months after ablation” write the authors in NEJM. However, the practice of switching anticoagulants “is cumbersome” and sometimes “impractical” for patients and physicians, they note.
RE-CIRCUIT is the largest trial to compare the uninterrupted use of NOACs to uninterrupted use of warfarin in the context of ablation. This randomised, open-label, multicentre, controlled study—funded by Boehringer Ingelheim—enrolled 704 patients scheduled for ablation of paroxysmal or persistent AF at 104 sites in 11 countries and randomly assigned patients to receive either dabigatran (150mg twice daily) or warfarin (target international normalised ratio, 2.0 to 3.0). Patients started anticoagulant therapy four to eight weeks before ablation and used it continuously for up to eight weeks after the procedure. The primary endpoint was the incidence of major bleeding events during and up to eight weeks after ablation and secondary endpoints included thromboembolic and other bleeding events.
In total, the researchers analysed data from 635 patients of the ablation set: 317 patients (mean age 59.1±10.4 years, 72.6% male) received dabigatran and 318 patients (mean age 59.3±10.3, 77% male) received warfarin. Dabigatran showed significant improvement over warfarin for the study’s primary endpoint, major bleeding events, and was associated with fewer periprocedural pericardial tamponades and groin haematomas than warfarin. “The mechanism of reducing major bleeding events with dabigatran may be related to the more specific mechanism of action (direct thrombin inhibition rather than a decrease in the production of several coagulation factors) and shorter half-life of dabigatran as compared with warfarin, as well as the presence of normal levels of factor VII and a stable anticoagulation effect,” write the researchers in NEJM.
With regards to secondary safety and efficacy endpoints, there were no events of stroke, systemic embolism, or transient ischaemic attack (TIA) in the dabigatran group and only one event of (TIA) in the warfarin group from the time of ablation until eight weeks after ablation. The incidence of minor bleeding events was similar in the two groups (18.6% of patients in the dabigatran group and 17% in the warfarin group). The composite incidence of major bleeding events and thromboembolic events, including stroke, systemic embolism or TIA, was lower in the dabigatran group than in the warfarin group (1.6% vs. 7.2% patients).
No deaths were reported.
Additionally, the authors noted the availability of idarucizumab (approved reversal agent for dabigatran) as a “potential advantage of the periprocedural use of dabigatran”. At ACC, Calkins said: “the availability of the specific reversal agent idarucizumab, while not needed in any patient in this trial, further motivates the adoption of uninterrupted dabigatran as the preferred anticoagulation strategy in patients undergoing AF ablation.”
Calkins has received lecture honoraria from Boehringer Ingelheim.