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In Memoriam: Participants Who Received Dabigatran Fect,” Write the Researchers in NEJM

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In Memoriam: Participants Who Received Dabigatran Fect,” Write the Researchers in NEJM April Issue App 17 36 Uninterrupted dabigatran Martin Burke: Artificial intelligence outperforms warfarin in atrial Page 9 fibrillation ablation Thomas F Deering: Results from RE-CIRCUIT, the largest trial to compare the uninterrupted use of a non-vitamin K antagonist oral anticoagulant (NOAC) with uninterrupted use of warfarin in Profile the context of atrial fibrillation (AF) ablation, have shown that uninterrupted dabigatran Page 12 (Pradaxa, Boehringer Ingelheim) was associated with fewer bleeding complications than uninterrupted warfarin before, during and after AF treatment with ablation. he findings offer evidence that major bleeding events with dabigatran Roberto Keegan: dabigatran is a safe and effec- may be related to the more specific The new LAHRS Ttive alternative to warfarin in mechanism of action (direct thrombin the context of AF ablation. The trial inhibition rather than a decrease in the Page 17 showed a 5.3% reduction in its pri- production of several coagulation fac- mary endpoint, major bleeding events tors) and shorter half-life of dabigatran during ablation or in the first two as compared with warfarin, as well as months after the procedure, with ma- the presence of normal levels of factor jor bleeds occurring in 1.6% of study VII and a stable anticoagulation ef- In memoriam: participants who received dabigatran fect,” write the researchers in NEJM. and 6.9% of patients on warfarin. With regards to secondary safety Mark E Josephson RE-CIRCUIT (Randomized evalu- and efficacy endpoints, there were ation of dabigatran etexilate compared no events of stroke, systemic embo- Mark E Josephson, a pioneer of clinical to warfarin in pulmonary vein abla- lism, or transient ischaemic attack cardiac electrophysiology (EP), passed tion: Assessment of an uninterrupted (TIA) in the dabigatran group and away at the age of 73 on 11 January 2017 periprocedural anticoagulation strat- Hugh Calkins only one event of TIA in the warfa- after a courageous battle with cancer. With egy) was presented by Hugh Calkins rin group from the time of ablation his passing, the EP community lost a great (Johns Hopkins Hospital, Baltimore, NEJM. However, the practice of until eight weeks after ablation. physician whose achievements will be USA) at the 2017 Scientific Session of switching anticoagulants “is cumber- The incidence of minor bleeding remembered for years to come. Andrew L the American College of Cardiology some” and sometimes “impractical” events was similar in the two groups Wit (Emeritus Professor of Pharmacology, (ACC; 17–19 March, Washington, for patients and physicians, they note. (18.6% of patients in the dabigatran Columbia University College of Physicians DC, USA) and simultaneously pub- RE-CIRCUIT is the largest trial group and 17% in the warfarin and Surgeons, New York, USA), a close lished in The New England Journal of to compare the uninterrupted use group). The composite incidence of professional colleague and friend of Medicine (NEJM). of NOACs to uninterrupted use of major bleeding events and throm- Josephson for over 40 years, writes this “I think it is great news for the warfarin in the context of AF abla- boembolic events, including stroke, tribute for Cardiac Rhythm News. field,” said Calkins. “There have been tion. This randomised, open-label, systemic embolism or TIA, was very few randomised studies focused multicentre, controlled study— lower in the dabigatran group than in ark E Joseph- on doing ablation procedures in fully funded by Boehringer Ingelheim— the warfarin group (1.6% vs. 7.2% son’s death is anticoagulated patients, and the use enrolled 704 patients scheduled for patients). No deaths were reported. Man extraordi- of NOACs has been increasing dra- ablation of paroxysmal or persistent Additionally, the authors noted nary loss to his family, matically. I expect these findings will AF at 104 sites in 11 countries and the availability of idarucizumab (ap- friends, colleagues and to encourage clinicians to quickly shift to randomly assigned patients to receive proved reversal agent for dabigatran) medicine and cardiology. doing this procedure with uninter- either dabigatran (150mg twice daily) as a “potential advantage of the His life was inextricably rupted use of NOACs.” or warfarin (target international periprocedural use of dabigatran”. intertwined with the Previous studies have shown normalised ratio, 2.0 to 3.0). Patients At ACC, Calkins said: “the avail- development of clinical the performance of AF ablation on started anticoagulant therapy four to ability of the specific reversal agent cardiac EP. Josephson was Mark E Josephson uninterrupted anticoagulation with a eight weeks before ablation and used idarucizumab, while not needed one of the pioneers of this (photo by Jan de Jonge) vitamin K antagonist (VKA)—such it continuously for up to eight weeks in any patient in this trial, further relatively new medical as warfarin—helps to minimise the after the procedure. The primary motivates the adoption of uninter- discipline which was born invention of the electrocar- risk of thromboembolic and bleeding endpoint was the incidence of major rupted dabigatran as the preferred in the 1960s. A recently diogram (ECG) in 1903, events, which are major complications bleeding events during and up to anticoagulation strategy in patients published book details his using deductive reasoning, of this procedure, commented Calkins. eight weeks after ablation and sec- undergoing AF ablation.” legacy and aptly identifies had established classifi- Data on the use of NOACs around the ondary endpoints included thrombo- Results of VENTURE AF the “Josephson School” cations of arrhythmias time of catheter ablation are limited. embolic and other bleeding events. (Cappato R et al. Eur Heart J of electrophysiologists according to sites of origin, “Most electrophysiologists have In total, the researchers analysed 2015;36(28):1805-11), the first trained by him, who will and hypothesised mecha- interrupted the dose of NOACs before data from 635 patients of the ablation prospective randomised trial of carry out his legacy.1 nisms.2 However, clinical catheter ablation, out of concern that set: 317 patients (mean age 59.1±10.4 uninterrupted rivaroxaban (Xarelto, When Josephson began EP was not born until the bleeding complications could lead to years; 72.6% male) received da- Bayer) and VKAs in patients with his electrophysiology 1960s when invention of worse outcomes in the presence of an bigatran and 318 patients (mean age non-valvular AF undergoing catheter training in the laboratory the electrode catheter ena- irreversible anticoagulant. High-risk 59.3±10.3; 77% male) received war- ablation, randomly assigned 248 of Anthony N Damato bled the heart to be electri- patients receiving NOACs often had farin. Dabigatran showed significant patients to either treatment and at the US Public Health cally stimulated directly their treatment changed over to VKAs improvement over warfarin for the showed the use of uninterrupted oral Service Hospital in Staten and electrical activity to periprocedurally, so that ablation could study’s primary endpoint, major bleed- rivaroxaban was feasible and event Island, USA, in 1971, be recorded from localised be performed with continuous anti- ing events, and was associated with rates were similar to those for unin- clinical EP was in its in- regions without thora- coagulation, and then were switched fewer periprocedural pericardial tam- terrupted VKA therapy. fancy. Brilliant minds over cotomy, in Amsterdam back to a NOAC, one or two months ponades and groin haematomas than Calkins has received lecture hono- five decades following the Continued on page 2 after ablation” write the authors in warfarin. “The mechanism of reducing raria from Boehringer Ingelheim. April Issue 2 Obituary 17 36 centred on the belief that an understanding of mechanisms is the foundation of future In memoriam: Mark E Josephson development of clinical cardiac EP. The Continued from page 1 treatment of patients should not be based and in Paris independently. In Amsterdam, only on published algorithms for the type of Dirk Durrer, Hein J Wellens and Reinier arrhythmia under consideration but should Schuilenburg showed that programmed pre- also involve an understanding of the basic mature stimuli using a specially designed electrophysiology. Those students who stimulator, applied to the atria or ventricles master these basics will be the ones who initiated tachycardia in patients with acces- will make innovative contributions and sory atrioventricular (AV) pathways.3 This devise new therapies in the future. To this was the origin of programmed electrical end he also wrote the “bible” of clinical stimulation (PES) to induce and terminate electrophysiology, Josephson’s Clinical tachycardias that were interpreted to be Andrew L Wit Mark Josephson teaching about Cardiac Electrophysiology, which is now in caused by reentrant excitation. Subsequent- complex arrhythmias, a course he gave its fifth edition.11 It is one man’s approach ly Wellens and his colleagues used PES and technique of endocardial catheter mapping with Hein J Wellens, sponsored by to the practice of clinical EP based on his intracardiac recordings to demonstrate that of VT.8 This approach led to recognition of Medtronic (photo by Rich Wawrzynski) many years of experience. It is extraordi- other supraventricular tachycardias as well the subendocardial origin of the majority of narily comprehensive. Another textbook as ventricular tachycardias could be induced
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