New Insights on Uninterrupted Anticoagulation in Left Atrial Catheter Ablation Procedures

Catheter ablation is a well-established treatment for symptomatic atrial fibrillation (AF). Guidelines have incorporated it for symptomatic AF class 1 or 2, depending on previous antiarrhythmic treatment and AF type.¹ The most important complications associated with AF ablation are major bleeding, periprocedural stroke or transient ischemic attack (TIA), and cardiac tamponade.^1,2 Although there is some variability in periprocedural oral anticoagulant (OAC) management in patients undergoing AF ablation, operators have recently moved towards a strategy of performing ablation under uninterrupted vitamin K antagonist (VKA) or novel OAC (NOAC) treatment, provided that the international normalized ratio is within the therapeutic range. In non-anticoagulated patients, initiating therapeutic anticoagulation 3–4 weeks before ablation may be considered.¹

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In a meta-analysis of 12 studies, 877 cases of uninterrupted anticoagulation using NOACs vs. VKAs for AF catheter ablation were associated with low rates of stroke/TIA (NOACs, 0.08%; VKAs, 0.16%) and similar rates of silent cerebral embolic events (NOACs, 8.0%; VKAs, 9.6%).³ However, major bleeding was significantly reduced with uninterrupted NOACs (0.9%) than with VKAs (2%). In the RE-CIRCUIT randomized clinical trial (RCT) comparing periprocedural NOAC vs. warfarin, the incidence of major bleeding events during and up to 8 weeks after ablation was significantly lower with dabigatran (1.6%) than with warfarin (6.9%).⁴ Other RCTs, such as VENTURE-AF with rivaroxaban, AXAFA-AFNET 5 with apixaban, and ELIMINATE-AF with edoxaban, showed similar event rates under uninterrupted NOACs compared with VKAs.^5–7 Overall, uninterrupted periprocedural NOACs were associated with a low incidence of stroke/TIA and a significant reduction in major bleeding compared with uninterrupted VKAs in patients undergoing AF. Furthermore, heparin bridging increases the risk of bleeding and should be avoided.

The term ‘uninterrupted’ is frequently used in clinical practice to describe regimens where 1 or 2 NOAC doses are omitted before ablation. In contrast, in the RCTs comparing uninterrupted NOACs vs. warfarin, NOAC administration before ablation was truly uninterrupted.⁴ Hence, there is no reason to recommend omitting 1 or 2 NOAC doses before ablation. After the procedure, administration of the first dose in the evening after ablation or on the following day (if this corresponds to the timing of the next dose according to the patient’s previous OAC regimen) appears to be safe.⁸ Additionally, the cardiac electrophysiologist can be confident that the patient be safely continued with an anticoagulant throughout a left atrial ablation procedure. Moreover, if uncontrollable hemorrhage occurs, it can be readily staunched using a highly effective reversal agent. The wide availability of a rapid reversal agent for dabigatran strongly supports its use, especially in those started on an OAC as prophylaxis for an ablation procedure.⁹

In this issue of the Journal, Shinohara et al¹⁰ investigate the effects of catheter ablation energy, comparing radiofrequency to cryoballoon, on myocardial injury, and evaluate the plasma concentrations of edoxaban and coagulative biomarkers measured immediately before ablation and on the day after ablation. Both myocardial injury and coagulative biomarkers increased after ablation, especially in the cryoballoon group, but no difference in the incidence of thrombotic or bleeding events was observed. Edoxaban can be safely used during ablation with radiofrequency or cryoballoon without increasing periprocedural complications.

This study was an exploratory subanalysis of the KYU-RABLE study, which provided evidence of the efficacy and safety of uninterrupted edoxaban administered once daily in the morning, with 1 dose delayed on the procedural day, in patients with AF undergoing ablation.¹¹ Moreover, the KYU-RABLE study showed that the coagulation status remained unchanged despite delaying 1 dose of edoxaban until after ablation.¹¹ Furthermore, another subanalysis of KYU-RABLE identified that the coagulation status remained unchanged regardless of the CHADS₂ (Congestive heart failure, Hypertension, age ≥75 years, Diabetes mellitus, prior Stroke or TIA or thromboembolism [doubled]) score or AF type.¹² In addition, edoxaban was associated with a low risk of periprocedural thromboembolic and bleeding complications in Japanese AF patients.

In the JACRE study, perioperative anticoagulation management using rivaroxaban with the last dose administered 24 h before the procedure and the dose resumed after the procedure or the following day was effective and safe in the Japanese population.¹³ Meanwhile, rivaroxaban was administered to 1,068 patients (95.5%) on the day before (day −1), 469 (41.9%) on the day of ablation (day 0), and 1,094 (97.9%) on the day after (day +1). Furthermore, all 3 common bleeding scores were associated with a periprocedural risk of ablation-related bleeding in AF patients. A modified HAS-BLED score ≥3 best distinguished high-risk patients from low-risk patients.¹⁴ The Figure is a summary of the scientific evidence of uninterrupted NOAC therapy: the results of 4 worldwide RCTs and 2 Japanese cohort studies.

Figure.

Summary of scientific evidence of uninterrupted NOAC therapy. The results of 4 worldwide RCTs and 2 Japanese cohort studies. AF, atrial fibrillation; NOAC, novel oral anticoagulant; RCT, randomized clinical trial; VKA, vitamin K antagonist.

This article demonstrated the effectiveness and safety of uninterrupted NOAC therapy in the Japanese Catheter Ablation Registry, a nationwide, multicenter, prospective, observational registry for improved patient care and clinical outcomes.¹⁵

Disclosures

Y. Kondo received lecture fees from Daiichi-Sankyo, Bayer, Abbott Medical Japan, Biotronik Japan, Boston Scientific, Japan Lifeline, and research funds from Daiichi-Sankyo. Y. Kobayashi received lecture fees from Abbott Medical Japan, Bayer Japan, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, and scholarship funds from Takeda Pharmaceutical, Abbott Medical Japan, Terumo, Otsuka Pharmaceutical, Boehringer Ingelheim, Astellas, Daiichi-Sankyo, Win International, Japan Lifeline, and Nipro.

The authors declare that there are no conflicts of interest with this article. Y. Kobayashi is a member of Circulation Journal’s Editorial Team.

IRB Information

None.

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