Washington – Uninterrupted dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation proved far superior to uninterrupted warfarin – the current standard – in the randomized multicenter RE-CIRCUIT trial, , reported at the annual meeting of the American College of Cardiology.
The primary study endpoint – the incidence of major bleeding events from the time of the first femoral puncture at the procedure’s start through the subsequent 8 weeks – occurred in 1.6% of the dabigatran (Pradaxa) group and 6.9% of the warfarin group, for an absolute 5.9% reduction in risk and a 77% relative risk reduction favoring the novel anticoagulant.
“This trial will definitely affect my own practice, and I think it will quickly affect the practices of electrophysiologists around the world,” declared Dr. Calkins, professor of cardiology and medicine and director of the clinical electrophysiology laboratory and the arrhythmia service at Johns Hopkins University, Baltimore.
RE-CIRCUIT (Randomized Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy) was a multicenter, prospective, international trial conducted in 635 atrial fibrillation (AF) patients who underwent catheter ablation at 104 sites. The trial was of necessity open label because of the need for frequent adjustments of warfarin dosing; however, outcome assessment was carried out by a blinded panel of six cardiologists and three neurologists.
Standard practice among AF ablationists is to continue oral anticoagulation periprocedurally because prior studies have convincingly shown that periprocedural interruption of warfarin in an effort to reduce bleeding results in a sharply increased risk of periprocedural stroke. So participants in RE-CIRCUIT were randomized to 4-8 weeks of uninterrupted anticoagulation with either dabigatran at 150 mg b.i.d. or warfarin with a target international normalized ratio (INR) of 2.0-3.0 prior to the ablation procedure, during it, and for 8 weeks afterward, at which time an individualized decision was made as to whether to stop or continue the drug.
Major bleeding events were defined by the International Society on Thrombosis and Hemostatis criteria. Most of these bleeds occurred within the first day or two after the procedure. Pericardial tamponades and groin hematomas were significantly less common with dabigatran.
The incidence of minor bleeding events was similar, at around 18% in the two treatment arms. No strokes or systemic embolisms occurred in the study. One patient on warfarin experienced a transient ischemic attack.
Dr. Calkins elaborated on why RE-CIRCUIT will change clinical practice: “A stroke is a terrible thing during an AF procedure and cardiac tamponade is the most common cause of death from the procedure. And now we have high-quality data showing that if you perform this procedure on uninterrupted dabigatran, the risk of stroke and other systemic embolic events is extremely low, and the rate of major bleeding was 77% less.
“Plus, the logistics of warfarin are a pain,” he continued. “If the patient presents on the day of ablation with an INR that’s too high, the procedure is canceled, and if they present with an INR that’s too low and the procedure is carried out, it’s done so with an increased stroke risk.”
Dr. Calkins said he suspects the sharp reduction in major bleeding events during and after AF catheter ablation is a class effect shared by the other NOACs. Studies with those agents are ongoing. But for now, the unique availability of an immediate reversal agent in the form of idarucizumab (Praxbind) for dabigatran in the event of uncontrolled major bleeding is a source of reassurance for operators and patients alike. The antidote was never required in RE-CIRCUIT, though, the cardiologist noted.
Discussant, called the trial “informative and helpful.”
“Something we’ve all been struggling with was that some concern was earlier raised that dabigatran might be associated with more thromboembolic events in this scenario. This study clearly refutes that concern,” observed Dr. Stevenson, director of the clinical cardiac electrophysiology program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Stevenson wondered whether the outcome differences between the two study groups could be explained by differences in operator techniques and tools. That’s highly unlikely, Dr. Calkins replied. Randomization was done patient by patient, not center by center.
Then why the big difference in major bleeding complications? Dr. Stevenson asked.
“It may be that, if you poke a hole when a patient is on a more forgiving anticoagulant like dabigatran, the bleeding doesn’t persist and turn into a tamponade, whereas if you poke a hole on warfarin it turns into a bigger problem,” Dr. Calkins responded. “When you think about it, warfarin really impacts the whole coagulation cascade through factors VII, IX, and X, so multiple coagulation factors are rendered impotent, whereas dabigatran is a direct thrombin inhibitor, so you’re selectively knocking out just one component of the coagulation cascade. It provides more leeway in preventing a small hole from turning into a big effusion,” he said.
The RE-CIRCUIT trial was funded by Boehringer Ingelheim. Dr. Calkins reported receiving lecture fees from that company and from Medtronic, and serving as a consultant to Medtronic, Abbott Medical, and AtriCure.
Simultaneously with Dr. Calkins’ presentation at ACC 17, the RE-CIRCUIT study was published online (N Engl J Med. 2017 Mar 19.