ABC | Volume 114, Nº3, March 2020

Short Editorial Uninterrupted Direct Oral Anticoagulants in Atrial Fibrillation Catheter Ablation: Ready for Prime Time Rhanderson Cardoso 1 and André D’Avila 2 Divisão de Cardiologia - Johns Hopkins Hospital, 1 Baltimore, Maryland - USA Serviço de Arritmia Cardíaca - Hospital SOS Cardio, 2 Florianópolis, SC - Brazil Short Editorial related to the article: Safety of Catheter Ablation of Atrial Fibrillation Under Uninterrupted Rivaroxaban Use Mailing Address: André D’Avila • Serviço de Arritmia Cardíaca / Hospital SOS Cardio - Rodovia, SC-401, 121. Postal Code 88030-000, Itacorubi, Florianópolis, SC - Brazil E-mail: andredavila@mac.com Keywords Atrial Fibrillation; Anticoagulants; Catheter Ablation; Rivaroxaban/therapeutic use. Catheter ablation is a well-established, safe, and effective strategy to achieve rhythm control in patients with symptomatic atrial fibrillation (AF) who are either intolerant or refractory to pharmacologic rhythm control or who wish to avoid long-term use of anti-arrhythmic drugs. Historically, when vitamin-K antagonists (VKAs) were the only option for oral anticoagulation, catheter ablation was performed after interruption of the VKA for several days and a transition (bridge) to subcutaneous or parenteral anticoagulation, typically with low-molecular- weight heparin. This strategy, however, was cumbersome and fraught with bleeding complications. Furthermore, the COMPARE randomized trial and observational studies showed that the thromboembolic risk was 10 to 15-fold higher with VKAs and heparin bridging as compared to uninterrupted VKAs. 1 After these results, uninterrupted VKAs with a therapeutic international normalized ratio (INR) became the standard of care for periprocedural anticoagulation, and patients would routinely undergo catheter ablation with INR ranging between 2 and 3.5. This option, however, also has two important setbacks. First, ablation becomes contingent on a therapeutic INR on the day of the procedure. A supra-therapeutic INR may entail a decision to postpone the procedure or administer blood products for correction, whereas a sub-therapeutic INR would typically imply deferring ablation to another day or require IV heparin until an ideal INR is reached. Second, the use of uninterrupted VKAs conflicts with the ever growing use of direct oral anticoagulants (DOACs). Electrophysiologists planning catheter ablation for patients on DOACs are faced with the following decision: (1) transition to VKAs for uninterrupted periprocedural anticoagulation or (2) continue periprocedural DOAC. This important question was addressed by Silva et al. 2 in this issue of the Brazilian Archives of Cardiology. They compared 130 consecutive patients with AF who underwent catheter ablation in a single center while receiving uninterrupted rivaroxaban to 110 patients in a historic control group who had previously undergone catheter ablation on uninterrupted VKA with a pre-procedure INR between 2 and 3.5. Major bleeding occurred in 1 (0.7%) and 2 (1.8%) individuals in the rivaroxaban and VKA groups, respectively. The event in the rivaroxaban group was a retroperitoneal hematoma requiring surgical drainage. In the VKA group, there was a femoral hematoma treated conservatively and a pericardial effusion requiring pericardiocentesis. One patient had an ischemic stroke in the rivaroxaban group (0.7%), while there were no thromboembolic events with VKAs. Other studies, including randomized trials with all four DOACs (rivaroxaban, apixaban, edoxaban, and dabigatran), have reached similar conclusions. In a meta-analysis including 12 studies and nearly 5,000 patients treated with uninterrupted VKAs or DOACs, the incidence of periprocedural stroke or transient ischemic attack was low, and it was not significantly different between the two groups (DOAC 0.08%, VKA 0.16%). 3 In a sub-cohort of patients who underwent routine post-procedure brain imaging, the incidence of clinically silent embolic events was also not significantly different between both groups (DOAC 8%; VKA 9.6%; OR 0.86; 95% CI 0.42 – 1.76). There was a lower incidence of major bleeding in those who received DOACs (0.9%) than in patients anticoagulated with VKAs (2%) (OR 0.50; 95% CI 0.30 – 0.84; p < 0.01). There was no difference between groups in the occurrence of pericardial tamponade (0.7%vs. 0.8%withDOACs and VKAs, respectively). 3 Altogether, we have learned several lessons from the study by Silva et al. 2 and similar studies in the literature. First, the incidence of periprocedural stroke with uninterrupted DOAC use is exceedingly low, well under 1%, and similar to that of uninterrupted VKAs. This represents a major improvement compared to the historic strategy of interrupting oral anticoagulation with a heparin bridge, where the incidence of thromboembolic events ranged from 1% to 5%. 1 The importance of this finding cannot be overstated. A low incidence of thromboembolic events is paramount when treating AF by catheter ablation, a procedure that is indicated almost exclusively for symptom control and not for life-saving purposes. It is noteworthy that the clinical significance of asymptomatic cerebral embolism in patients who undergo catheter ablation is unclear at this point. Further studies should examine long-term clinical outcomes and cognitive function in those who have clinically silent cerebral embolic events. Second, the incidence of major hemorrhagic complications with uninterrupted DOACs is also low, and it is comparable to, if not better than, that of uninterrupted VKAs. In the present study, a power calculation, with two-sided alpha of 0.05 and a 2.5% event rate in control group, would yield an estimated power of only 3% to detect a 1% difference in major bleeding events between groups with the sample size DOI: https://doi.org/10.36660/abc.2020011 443