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Background: To assess long-term effectiveness and safety of edoxaban in Europe., Methods and Results: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA 2 DS 2 -VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%)., Conclusions: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics., Competing Interests: Declaration of competing interest P.K. receives research support for basic, translational, and clinical research projects from European Union Big- Data@Heart (grant agreement EU IMI 116074) CATCH ME (grant agreement ID: 633196) AFFECT-EU (grant agreement ID: 847770); Leducq foundation, Medical Research Council (UK); German Centre for Cardiovascular Research supported by the German Ministry of Education and Research; from several drug and device companies active in atrial fibrillation and has received honoraria from several such companies in the past, but not in the last three years. P.K. is listed as inventor on two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). P.K. is employed as Director of the Department of Cardiology, University Heart and Vascular Centre UKE Hamburg and Professor of Cardiovascular Medicine (part-time), University of Birmingham, UK. He is Speaker of the board of AFNET, Germany, and Board member of the ESC. A.B. is founder and clinical trial design advisor of Amore Health Ltd., reports support from Daiichi Sankyo for attending meetings and advisory boards; receives honorarium from Daiichi Sankyo, Pfizer, BMS, Bayer, Novartis, Roche, Napp, Boehringer Ingelheim for lecturing and scientific advice outside the submitted work. C.d.A. has received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Atricure, Biosense Webster, Boston Scientific, Acutus Medical and research grants on behalf of the centre from Biotronik, Medtronic Abbott, Microport, Boston Scientific, Biosense Webster, Acutus Medical. J.R.d.G. reports personal fees from Daiichi Sankyo during the conduct of the study; grants from Abbott, Atricure, Bayer, Boston Scientific, Daiichi Sankyo, Johnson & Johnson and Medtronic; personal fees from Atricure, Bayer, Berlin Chemie, Daiichi Sankyo, Johnson & Johnson, Menarini, Medtronic, Novartis, and Servier; and other from RhythmCARE outside the submitted work. J.C.D. has received honoraria for lectures from Bayer, Boehringer Ingelheim, and Bristol Myers Squibb. J.C.D. has also received research grants from Boston Scientific, Sorin Group, Biotronik, and Abbott. P.K. has received speaker's and committee membership from Daiichi Sankyo, and received consulting fee (<€5000) from Alexion and Novo Nordisk. He is the Lead Investigator of the HRB Stroke Clinical Trials Network Ireland, which has received grant funding from the Irish government, Irish Heart Foundation, Daiichi Sankyo, Bayer, Boehringer Ingelheim, Pfizer, Bristol Myers Squibb, Amgen, and A Menarini. E.L.-d.-S. reports personal fees from Daiichi Sankyo; grants and personal fees from Servier, ZOLL Medical, and Becton Dickinson; grants from AstraZeneca, MedImmune LLC and Novartis, during the conduct of the study. P.M. is an ETNA-AF investigator and has received lecture and research fees from Daiichi Sankyo, Bayer, Boehringer Ingelheim, and Pfizer/BMS. E.-M.F., M.L., P.L., and R.S. are employees of Daiichi Sankyo Europe GmbH, Munich, Germany. J.S. has received consultant and/or speaker fees from Abbott, Alexion, Astra-Zeneca, Bayer, Berlin-Chemie, Biosense Webster, Biotronik, Boehringer-Ingelheim, Boston Scientific, BMS, Daiichi Sankyo, Medscape, Medtronic, Menarini, Merck/MSD, Organon, Pfizer, Saja, Servier, and WebMD. He reports ownership of Swiss EP and CorXL. J.W. reports personal fees and non-financial support from Biotronik, Boehringer Ingelheim, and Daiichi Sankyo; personal fees from Akzea, Bayer Vital, MSD, Berlin-Chemie and Siemens Healthineers, outside the submitted work. T.W.W. has received fees, honoraria and research funding from AstraZeneca, Boehringer Ingelheim, Bayer, Bristol Myers Squibb/Pfizer, Daiichi Sankyo, Medtronic, Menarini Pharma, Novartis, and Sanofi Aventis. R.D.C. reports grants, personal fees and non-financial support from Daiichi Sankyo, during the conduct of the study; and reports consulting fees, honoraria and other financial or non-financial interests: Amgen, Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi Sankyo, Janssen, Milestone, Novartis, Sanofi, Menarini, Guidotti, and Roche, outside the submitted work. Consultancy fees from Daiichi Sankyo Europe for the Chairing of the ETNA-AF Europe registry., (Copyright © 2023. Published by Elsevier B.V.)

Despite marked progress in the management of atrial fibrillation (AF), detecting AF remains difficult and AF-related complications cause unacceptable morbidity and mortality even on optimal current therapy. This document summarizes the key outcomes of the 8th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eighty-three international experts met in Hamburg for 2 days in October 2021. Results of the interdisciplinary, hybrid discussions in breakout groups and the plenary based on recently published and unpublished observations are summarized in this consensus paper to support improved care for patients with AF by guiding prevention, individualized management, and research strategies. The main outcomes are (i) new evidence supports a simple, scalable, and pragmatic population-based AF screening pathway; (ii) rhythm management is evolving from therapy aimed at improving symptoms to an integrated domain in the prevention of AF-related outcomes, especially in patients with recently diagnosed AF; (iii) improved characterization of atrial cardiomyopathy may help to identify patients in need for therapy; (iv) standardized assessment of cognitive function in patients with AF could lead to improvement in patient outcomes; and (v) artificial intelligence (AI) can support all of the above aims, but requires advanced interdisciplinary knowledge and collaboration as well as a better medico-legal framework. Implementation of new evidence-based approaches to AF screening and rhythm management can improve outcomes in patients with AF. Additional benefits are possible with further efforts to identify and target atrial cardiomyopathy and cognitive impairment, which can be facilitated by AI., Competing Interests: Conflict of interest: RBS has received lecture fees and advisory board fees from BMS/Pfizer outside this work and has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union's Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (8121710103); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239).EAM is employee of Daiichi Sankyo Europe GmbH producing and marketing an oral anticoagulant (edoxaban). EA has received consulting / speaker fees for Biosense Webster. GB has received speaker's fees of small amount from Boston, Bayer, Daiichi, Boehringer. SB is consultant for Medtronic, Boston Scientific, Microport, and Zoll. JC has received consulting fees / honoraria fees from Acesion, Allergan, Alta Thera, Arca, lncarda, Menarini, Milestone, Sanofi, Bayer, Daiichi Sankyo, Pfizer, Abbott, Biosense Webster, Biotronik, Boston Scientific, Lilly, Medtronic, Johnson and Johnson. BC has received in kind contribution for research Support from iRhythm. WC has received advisory board fees for Roche Diagnostics AG. MDM is employee of Medtronic. SZB has received fees as member of Advisory Board in Bristol Myers Squibb-Pfizer. DD has received fees from Abbott, Astra Zenica, Bayer, Bosten Scientific, Bristol Myers Squibb-Pfizer, Medtonic, Zoll. LE has received lecture Honoria from Medtronic, Biotronik, Boston Scientific, Boehringer Ingelheim, Daiichy Sankyo, Bayer, MMS, Pfizer, Sanofi and received research grants from DFG and DGK. CE is employee of Preventicus GmbH. LF has received institutional research grants and non-financial support from European Union, DFG, British Heart Foundation, Medical Research Council (UK), NIHR, and several biomedical companies. The Institute of Cardiovascular Research, University of Birmingham, has received an Accelerator Award by the British Heart Foundation M/18/2/34218. LF is listed as inventor of two patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). BF receiving fees from Bristol-Myers Squibb and Pfizer Alliance, Bayer, Daiichi Sankyo, Omron. (largely speaker fees and travel support for speaking at session or official satellites of large international/continental society meetings) and investigator-initiated research grants to the institution from Bristol-Myers and Squibb and Pfizer Alliance and Ownership / Employee of Nil. LG and AZ are employees of Roche Diagnostics International Ltd. AG has received funding from Daiichi Sankyo, Astra Zenica, Bayer, Bristol Myers Squibb-Pfizer, Viola, Medtonic, Berlin Charitè. JHS has received Advisory board fees in Medtronic and Speaker fee from Medtronic. KGH has received fees from Abbott, Alexion, AMARIN, AstraZeneca, Bayer, Biotronik, Boehringer Ingelheim, Bristol-Myers-Squibb, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Pfizer, Premier Research, SUN Pharma and W. L. Gare & Associates and Research Grants from Bayer Vital, Sanofi-Aventis. JSH received fees from Boston Scientific, Servier, Bayer, Myokardia, Bristol-Myers-Squibb, Pfizer, and research grants from Medtronic, Boston Scientific, Bristol-Myers-Squibb, Abbott. HH has received lecture and consultancy fees from Abbott, Biotronik, Bristol-Myers-Squibb- Pfizer, Medscape, Daiichi Sankyo, Springer Healthcare Ltd and receive un conditional research grants through the Univerity of Antwerp and/or University of Hasselt from Abbott, Bayer, Biotronik, Biosense-Webster, Fibrickeck/Qompium, Medtronic, Bristol-Myers-Squibb- Pfizer, Boston Scientific, Daiichi Sankyo and Boehringer Ingelheim. RH has received speacker fees from BI, Bayer and Bristol-Myers-Squibb- Pfizer and AZ. TH is CEO of Preventicus GmbH. DK has received funding from Bayer, AtriCure, Protherics Medicines Development and Myokardia and Research grant from rants from the National Institute for Health Research (NIHR CDF-2015-08-074 RATE-AF; NIHR HTA-130280 DaRe2THINK; NIHR EME- 132974 D2T-NV), the British Heart Foundation (PG/17/55/33087 and AA/18/2/34218), EU/EFPIA IMI (BigData@Heart 116074),the European Society of Cardiology supported by educationalgrants from Boehringer Ingelheim/BMS-Pfizer Alliance/Bayer/Daiichi Sankyo/Boston Scientific, the NIHR/the University of Ox- ford Biomedical Research Centre, and British Heart Foundation/ the University of Birmingham Accelerator Award (STEEER-AF NCT04396418), Amomed Pharma, and IRCCS San Raffaele/Menarini (beta-blockers in Heart Failure Collaborative Group NCT0083244). MK is employee of Bristol-Myers and Squibb. CL has received fees from medtonic, Boston Scientific, Biotronik and Bristol-Myers and Squibb- Pfizer and research grants from Rennes Univerity, Metronik, Biotonik and Boston Scientific. DL has received research grant for EHRA-PATHS, NovoNordisk Young Investigator Award. MLL has received lecture fees from Bristol-Myers and Squibb and research grant from H2020 AFFECT-EU (grant No. 847770). SM has received research grant from Daiichi Sankyo (EPDAURUS IIT) and Bristol-Myers and Squibb (APPROACH ACS AF IIT). JLM has received Abbott, Boston Scientific, Biotronik, Boehringer Ingelheim, Sanofi, Microport and received research grants from Medtronic, Abbott, Microport, Biosense. RM is employee of Medtronic. LM is Stockholder for Galgomedical and Corify and receiving consuting fees from Abbott, Biosense-Webster, Bosten Scientific, Medtronik and receiving research grants from Abbott, Biosense-Webster, Bosten Scientific, Medtronik. LN has received consulting fees from Bristol-Myers and Squibb- Pfizer. GP is employee of Bayer AG. HP has received consulting fees from Abbott, Biosense-Webster, Bosten Scientific, Medtronik and receiving research grants from Abbott, Bayer, Biosense-Webster, Bosten Scientific, Medtronik, Bristol-Myers and Squibb- Pfizer. MR has received consulting fees for Medtonic, Arca BiopharmaInc, Roche and received research grants from Dutch Heart Foundation: RACE V, RED-CVD, CVON-AI, DECISION studies; grant from SJM/Abbott to institution: VIP-HF study; Grant for Medtronic to institution: Cryoballoon AF registry/biobank study. The other authors declare that there is no conflict of interest.LR has received research grants from Canadian Insititute of Health research and Byer Inc. U.S. received consultancy fees or honoraria from Università della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited, (United Kingdom), Bayer Healthcare (Germany). U.S. is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht and Research grant from the Dutch Heart Foundation (CVON RACE V, CVON2014–09) European Union's Horizon 2020 Research and Innovation Program granted to MS under the Marie Sklodowska-Curie grant agreement #813716 (TRAIN-HEART Innovative Training Network), and various other programs of the European Union granted to US (ITN Network Personalize AF: Personalized Therapies for Atrial Fibrillation: a translational network – grant #860974; CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly – grant #633196; MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation – grant #965286; REPAIR: Restoring cardiac mechanical function by polymeric artificial muscular tissue – grant #952166). DS has received consultation fees from Biosense Webster, Abbott, Boston Scientific, Consultant with stock option: SentiAR, Arga Medtech. RS is employee of Daiichi Sankyo Europe GmbH. DS has received consultation fees from Boston Scientific, Abbott and Research grant from Biosense Webster. ES has received lecture fees from Bayer, Bristol-Myers and Squibb- Pfizer, Boehringer Ingelheim, Johnson & Johnson, Merck Sharp & Dohme and Sanofi. DT has received lecture fees from Bayer Vital, Bristol-Myers and Squibb- Pfizer, Daiichi Sankyo, Medtonic, Zoll CMS, Sanofi, St. Jude Medical and research grant from Daiichi Sankyo. MTH is employee/owner of American Foundation of women's Health /StopAfib.org and employee/owner of True Hills Inc.. BV is employee of Bayer AG. RW has received consultation fees from Boston Scientific, Biotronic, Pfizer, Daiichi Sankyo, Bayer, Adagio Medical and Research grant from Bristol-Myers and Squibb- Pfizer, Boston Scientific. CW has received consulation fees from Biotronik, Boston Scientific, Novartis and research grant from BMBF, AFNET, DZHK, Biotronik. MW is employee and shareholder of Sanofi. SW has received Consulting fees from Boston Scientific, Abbott, Bayer, Bristol-Myers and Squibb- Pfizer, Boehringer Ingelheim and research grant from Boston Scientific. HW is employee and stockholder of Pfizer Germany. MDZ has received advisory and speaker fee from Bristol-Myers and Squibb- Pfizer. PK reports grants and non-financial support from BMBF (German Ministry of Education and Research), grants from Sanofi and Abbott, grants and non-financial support from EHRA (European Heart Rhythm Association), and grants from German Heart Foundation and DZHK (German Center for Cardiovascular Research), during the conduct of the study, and grants from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and non-financial support from German Centre for Heart Research, outside the submitted work; in addition, P.K. has a patent Atrial Fibrillation Therapy WO 2015140571 issued to University of Birmingham and a patent Markers for Atrial Fibrillation WO 2016012783 issued to University of Birmingham., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: This subgroup analysis of the ENTRUST-AF PCI trial (ClinicalTrials.gov Identifier: NCT02866175; Date of registration: August 2016) evaluated type of AF, and CHA 2 DS 2 -VASc score parameters as predictors for clinical outcome., Methods: Patients were randomly assigned after percutaneous coronary intervention (PCI) to either edoxaban (60 mg/30 mg once daily [OD]; n = 751) plus a P2Y 12 inhibitor for 12 months or a vitamin K antagonist [VKA] (n = 755) plus a P2Y 12 inhibitor and aspirin (100 mg OD, for 1-12 months). The primary outcome was a composite of major/clinically relevant non-major bleeding (CRNM) within 12 months. The composite efficacy endpoint consisted of cardiovascular death, stroke, systemic embolic events, myocardial infarction (MI), and definite stent thrombosis., Results: Major/CRNM bleeding event rates were 20.7%/year and 25.6%/year with edoxaban and warfarin, respectively (HR [95% CI]: 0.83 [0.654-1.047]). The event rates of composite outcome were 7.26%/year and 6.86%/year, respectively (HR [95% CI]): 1.06 [0.711-1.587]), and of overall net clinical benefit were 12.48%/year and 12.80%/year, respectively (HR [(95% CI]: 0.99 [(0.730; 1.343]). Increasing CHA 2 DS 2 -VASc score was associated with increased rates of all outcomes. CHA 2 DS 2 -VASc score ≥ 5 was a marker for stent thrombosis. Paroxysmal AF was associated with a higher occurrence of MI (4.87% versus 2.01%, p = 0.0024)., Conclusion: After PCI in AF patients, increasing CHA 2 DS 2 -VASc score was associated with increased bleeding rates and CHA 2 DS 2 -VASc score (≥ 5) predicted the occurrence of stent thrombosis. Paroxysmal AF was associated with MI. These findings may have important clinical implications in AF patients.

Aims: The risk of developing atrial fibrillation (AF) and its complications continues to increase, despite good progress in preventing AF-related strokes., Methods and Results: This article summarizes the outcomes of the 7th Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA) held in Lisbon in March 2019. Sixty-five international AF specialists met to present new data and find consensus on pressing issues in AF prevention, management and future research to improve care for patients with AF and prevent AF-related complications. This article is the main outcome of an interactive, iterative discussion between breakout specialist groups and the meeting plenary. AF patients have dynamic risk profiles requiring repeated assessment and risk-based therapy stratification to optimize quality of care. Interrogation of deeply phenotyped datasets with outcomes will lead to a better understanding of the cardiac and systemic effects of AF, interacting with comorbidities and predisposing factors, enabling stratified therapy. New proposals include an algorithm for the acute management of patients with AF and heart failure, a call for a refined, data-driven assessment of stroke risk, suggestions for anticoagulation use in special populations, and a call for rhythm control therapy selection based on risk of AF recurrence., Conclusion: The remaining morbidity and mortality in patients with AF needs better characterization. Likely drivers of the remaining AF-related problems are AF burden, potentially treatable by rhythm control therapy, and concomitant conditions, potentially treatable by treating these conditions. Identifying the drivers of AF-related complications holds promise for stratified therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Aims: This post hoc analysis of ELIMINATE-AF evaluated requirements of unfractionated heparin (UFH) and procedure-related bleeding in atrial fibrillation (AF) patients undergoing ablation with uninterrupted edoxaban or vitamin K antagonist (VKA) therapy., Methods and Results: Patients were randomized 2:1 to once-daily edoxaban 60 mg (or dose-reduced 30 mg) or dose-adjusted VKA (target international normalized ratio: 2.0-3.0). Uninterrupted anticoagulation was mandated for 21-28 days' pre-ablation and 90 days' post-ablation. During ablation, UFH administration targeted an activated clotting time (ACT) of 300-400 s. Periprocedural bleeding was differentiated between procedure-related (bleeding at puncture side, cardiac tamponade) and unrelated events. Of 614 randomized patients, 553 received study drug and underwent catheter ablation (edoxaban n = 375; VKA n = 178). The median (Q1-Q3) time from last dose to ablation procedure was 14.8 (13.3-16.5) vs. 16.5 (14.8-19.5) h (edoxaban vs. VKA group, respectively). Mean ACT (SD) ≥300 s was observed in 52% edoxaban- vs. 76% VKA-treated patients, despite a higher mean (SD) UFH dose in the edoxaban vs. VKA group [14 261 (6397) IU vs. 11 473 (4300) IU; exploratory P-value < 0.0001]. In the edoxaban group, 13 patients (3.5%) had procedure-related bleeds of whom 9 had received an UFH dose above the median (13 000 IU). In the VKA arm, 7 patients (3.9%) had procedure-related bleeds of whom 3 had received an UFH dose above the median (10 225 IU)., Conclusion: The rate of procedure-related major/clinically relevant non-major bleeding did not differ between the treatment arms despite higher doses of UFH used with edoxaban vs. VKA to achieve a target ACT during AF ablation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To compare the safety and efficacy of edoxaban combined with P2Y12 inhibition following percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF) presenting with an acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)., Methods and Results: In this pre-specified sub-analysis of the ENTRUST-AF PCI trial, participants were randomly assigned 1:1 to edoxaban- or vitamin K antagonist (VKA)-based strategy and randomization was stratified by ACS (edoxaban n = 388, VKA n = 389) vs. CCS (edoxaban n = 363, VKA = 366). Participants received edoxaban 60 mg once-daily plus a P2Y12 inhibitor for 12 months, or VKA combined with a P2Y12 inhibitor and aspirin 100 mg (for 1-12 months). The primary bleeding endpoint at 12 months occurred in 59 (15.2%) vs. 79 (20.3%) ACS patients [hazard ratio (HR): 0.73, 95% confidence interval (CI): 0.59-1.02, P = 0.063], and in 69 (19.0%) vs. 73 (19.9%) CCS patients (HR: 0.94, 95%CI: 0.68-1.31, P = 0.708) with edoxaban- and VKA-based therapy, respectively [P for interaction (P-int) = 0.2741]. The main secondary endpoint (composite of CV death, myocardial infarction, stroke, systemic embolic events, or definite stent thrombosis) in ACS patients was 33 (8.5%) vs. 28 (7.2%) (HR: 1.16, 95%CI: 0.70-1.92), compared with 16 (4.4%) vs. 18 (4.9%) (HR: 0.91, 95%CI: 0.47-1.78) CCS patients with edoxaban and VKA-based therapy, respectively (P-int = 0.5573)., Conclusions: In patients with AF who underwent PCI, the edoxaban-based regimen, as compared with VKA-based regimen, provides consistent safety and similar efficacy for ischaemic events in patients with AF regardless of their clinical presentation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We aimed to assess the safety of edoxaban in combination with P2Y12 inhibition in patients with atrial fibrillation who had percutaneous coronary intervention (PCI)., Methods: ENTRUST-AF PCI was a randomised, multicentre, open-label, non-inferiority phase 3b trial with masked outcome evaluation, done at 186 sites in 18 countries. Patients had atrial fibrillation requiring oral anticoagulation, were aged at least 18 years, and had a successful PCI for stable coronary artery disease or acute coronary syndrome. Participants were randomly assigned (1:1) from 4 h to 5 days after PCI using concealed, stratified, and blocked web-based central randomisation to either edoxaban (60 mg once daily) plus a P2Y12 inhibitor for 12 months or a vitamin K antagonist (VKA) in combination with a P2Y12 inhibitor and aspirin (100 mg once daily, for 1-12 months). The edoxaban dose was reduced to 30 mg per day if one or more factors (creatinine clearance 15-50 mL/min, bodyweight ≤60 kg, or concomitant use of specified potent P-glycoprotein inhibitors) were present. The primary endpoint was a composite of major or clinically relevant non-major (CRNM) bleeding within 12 months. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of their assigned study drug. This trial is registered with ClinicalTrials.gov, NCT02866175, is closed to new participants, and follow-up is completed., Findings: From Feb 24, 2017, through May 7, 2018, 1506 patients were enrolled and randomly assigned to the edoxaban regimen (n=751) or VKA regimen (n=755). Median time from PCI to randomisation was 45·1 h (IQR 22·2-76·2). Major or CRNM bleeding events occurred in 128 (17%) of 751 patients (annualised event rate 20·7%) with the edoxaban regimen and 152 (20%) of 755 patients (annualised event rate 25·6%) patients with the VKA regimen; hazard ratio 0·83 (95% CI 0·65-1·05; p=0·0010 for non-inferiority, margin hazard ratio 1·20; p=0·1154 for superiority)., Interpretation: In patients with atrial fibrillation who had PCI, the edoxaban-based regimen was non-inferior for bleeding compared with the VKA-based regimen, without significant differences in ischaemic events., Funding: Daiichi Sankyo., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aims: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested., Methods and Results: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62)., Conclusion: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients with atrial fibrillation (AF) are at an approximately 0.5% to 3% increased risk of thromboembolism during and immediately after catheter ablation. Treatment guidelines recommend periprocedural oral anticoagulation plus unfractionated heparin during ablation. Rivaroxaban and dabigatran are the only non-vitamin K oral anticoagulants for which there are randomized controlled trials assessing uninterrupted anticoagulation in patients undergoing catheter ablation of AF. Edoxaban, a direct factor Xa inhibitor, is noninferior vs warfarin for the prevention of stroke or systemic embolism with less major bleeding in patients with nonvalvular AF. The ELIMINATE-AF (Evaluation of Edoxaban Compared With VKA in Subjects Undergoing Catheter Ablation of Nonvalvular Atrial Fibrillation) trial is a multinational, multicenter, prospective, randomized, open-label, parallel-group, blinded-endpoint evaluation (PROBE) study to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for a dose reduction) vs vitamin K antagonists (VKA) in patients with nonvalvular AF undergoing catheter ablation (http://www.ClinicalTrials.gov: NCT02942576). A total of 560 patients are planned for randomization to edoxaban or VKA (2:1 ratio) to obtain 450 patients fully compliant with the protocol. Patients will complete 21 to 28 days of anticoagulation prior to the ablation and a 90-day post-ablation period. The primary efficacy endpoint is the composite of all-cause death, stroke, and major bleeding. The primary safety endpoint is major bleeding. A magnetic resonance imaging substudy will assess the incidence of silent cerebral lesions post-ablation. ELIMINATE-AF will define the efficacy and safety of edoxaban for uninterrupted oral anticoagulation during catheter ablation of AF., (© 2018 Wiley Periodicals, Inc.)

Background: The optimal antithrombotic treatment after percutaneous coronary intervention (PCI) with stenting in patients with atrial fibrillation (AF) is unknown. In the ENGAGE AF-TIMI 48 trial, edoxaban was noninferior to a vitamin K antagonist (VKA) with respect to the prevention of stroke or systemic embolism and was associated with significantly lower rates of bleeding and cardiovascular death in patients with nonvalvular AF. The effects of edoxaban in combination with single- or dual-antiplatelet therapy in the setting of PCI are unexplored., Design: The ENTRUST-AF PCI trial is a multinational, multicenter, randomized, open-label phase 3b trial with blinded end point evaluation involving 1,500 patients on oral anticoagulation for AF. Patients are randomized between 4 hours and 5 days after successful PCI to either an edoxaban-based strategy (experimental arm; 60 mg [or 30 mg according to dose reduction criteria] once daily plus a P2Y 12 antagonist [default clopidogrel, 75 mg once daily] for 12 months) or a VKA-based strategy (control arm; VKA plus a P2Y 12 antagonist [as above] plus acetylsalicylic acid [100 mg once daily] for 30 days to 12 months). The primary safety end point is the incidence of International Society on Thrombosis and Haemostasis-defined major or clinically relevant nonmajor bleeding. The main efficacy end point is the composite of cardiovascular death, stroke, systemic embolic events, spontaneous myocardial infarction, and definite stent thrombosis., Summary: The ENTRUST-AF PCI trial tests the hypothesis that an edoxaban-based antithrombotic strategy reduces the risk of bleeding complications after PCI compared with VKA plus conventional dual-antiplatelet therapy in patients with AF in need of oral anticoagulation. The relative risk of ischemic events between groups will be compared., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)