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Background: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear., Methods and Results: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients)., Conclusions: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

Aims: Anticoagulation can prevent stroke and prolong lives in patients with atrial fibrillation (AF). However, anticoagulated patients with AF remain at risk of death. The aim of this study was to investigate the causes of death and factors associated with all-cause and cardiovascular death in the XANTUS population., Methods and Results: Causes of death occurring within a year after rivaroxaban initiation in patients in the XANTUS programme studies were adjudicated by a central adjudication committee and classified following international guidance. Baseline characteristics associated with all-cause or cardiovascular death were identified. Of 11 040 patients, 187 (1.7%) died. Almost half of these deaths were due to cardiovascular causes other than bleeding (n = 82, 43.9%), particularly heart failure (n = 38, 20.3%) and sudden or unwitnessed death (n = 24, 12.8%). Fatal stroke (n = 8, 4.3%), which was classified as a type of cardiovascular death, and fatal bleeding (n = 17, 9.1%) were less common causes of death. Independent factors associated with all-cause or cardiovascular death included age, AF type, body mass index, left ventricular ejection fraction, hospitalization at baseline, rivaroxaban dose, and anaemia., Conclusion: The overall risk of death due to stroke or bleeding was low in XANTUS. Anticoagulated patients with AF remain at risk of death due to heart failure and sudden death. Potential interventions to reduce cardiovascular deaths in anticoagulated patients with AF require further investigation, e.g. early rhythm control therapy and AF ablation., Trial Registration Numbers: NCT01606995, NCT01750788, NCT01800006., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA)., Methods and Results: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF., Conclusions: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF., Competing Interests: Conflict of interest The 9th AFNET/EHRA consensus conference was partially supported by the European Union MAESTRIA project (grant agreement 965286) to AFNET. The following participants and authors are employees of companies active in cardiovascular health as indicated in their affiliations: M.D.M., E.D., C.E., G.H., L.H.H., T.H., R.H.v.L., M.W., and H.W. P.K. was partially supported by the European Union AFFECT-AF (grant agreement 847770) and MAESTRIA (grant agreement 965286), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers DZHK FKZ 81X2800182, 81Z0710116, and 81Z0710110), German Research Foundation (Ki 509167694), and Leducq Foundation. He receives research support for basic, translational, and clinical research projects from several drug and device companies active in AF and has received honoraria from several such companies in the past, but not in the last 3 years. He is listed as an inventor on two issued patents held by the University of Hamburg (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). J.G.A. was partially supported by the Canadian Arrhythmia Network and the Michael Smith Foundation for Health Research, Baylis Medical. He receives consulting fees/honoraria from Bayer, BMS/Pfizer Alliance, Servier, and Medtronic Inc. E.A. receives consulting fees/honoraria from Biosense Webster and Bayer. G.B. receives consulting fees/honoraria from Bayer, BMS, Boston Scientific, Daiichi Sankyo, Sanofi, and Janssen. A.J.C. receives consulting fees/honoraria from Bayer, Pfizer/BMS, Daiichi Sankyo, Menarini, Sanofi, Boston Scientific, Biosense Webster, Abbott, Acesion Pharma, Huya Bio, and Milestone. V.C. receives consulting fees/honoraria from Bayer, Boehringer Ingelheim, and Ever Pharma (paid to the institution of employment). W.D. receives consulting fees/honoraria from Reata and research grants from MicroPort, Boston Scientific, and Abbott. S.Z.D. receives consulting fees from BMS/Pfizer, Cortrium, and Acesion Pharma and speaker fees from MS/Pfizer and Bayer. He is listed as a medical advisor for Vital Beats. Dobromir D. receives consulting fees/honoraria from Elsevier, Springer Healthcare Ltd, and Daiichi Sankyo and research grants as follows: four NIH grants (partially) from Baylor College of Medicine, Houston; one NIH grant from UC Davis, one NIH grant from the University of Minnesota, and one EU-Project H2020. David D. receives consulting fees/honoraria from Abbott, Astra Zeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, CVRx, Medtronic, MicroPort, and Zoll and research grants from Roche, CVRx, and Zoll. L.E. has received lecture fees from various companies in AF in the past but none related to the present work. L.F. receives consulting fees/honoraria from Roche (paid to the institution of employment). She is currently employed at the UKE and previously at the University of Birmingham. She was partially supported by the European Union AFFECT-EU (grant agreement 847770), MAESTRIA (grant agreement 965286), CATCH ME (grant agreement 633196), and the British Heart Foundation (AA/18/2/3218). D.F.-R. receives research grants from Abbott. He is listed as an inventor on two issued patents: EP3636147A1 (method for the identification of cardiac fibrillation drivers and/or the footprint of rotational activations) and PCT/EP2022/071364 (system and method of assessment of electromechanical remodelling). A.G. receives consulting fees/honoraria from Daiichi Sankyo, Bayer, BMS/Pfizer, Medtronic, Abbott, and Boston Scientific and was partially supported by the European Union MAESTRIA (grant agreement 965286). K.G.H. receives consulting fees/honoraria from Abbott, Alexion, Amarin, Astra Zeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, BMS/Pfizer, Daiichi Sankyo, Edwards Lifesciences, Medtronic, Novaris, Portola, Premier Research, Sanofi, SUN Pharma, and W. L. Gore and Associates. J.S.H. receives speaking fees from BMS/Pfizer, Bayer, Servier, and Boston Scientific and consulting fees from Bayer and Boston Scientific. He receives research grants from BMS/Pfizer, Servier, Novartis, Boston Scientific, and Medtronic. H.H. receives lecture and consulting fees from Bayer, Biotronik, BMS/Pfizer, Daiichi Sankyo, Milestone Pharmaceuticals, Centrix India, C.T.I. Germany, ESC, Medscape, and Springer Healthcare Ltd. He receives research grants (paid to the institution of employment, University of Antwerp and/or University of Hasselt) from Abbott, Bayer, Biosense Webster, Boston Scientific, Daiichi Sankyo, Fibricheck/Qompium, Medtronic, and BMS/Pfizer. Z.H. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, and Roche Diagnostics. He was partially supported by The Swedish Society for Medical Research (S17-0133), Hjärt-Lungfonden (The Swedish Heart-Lung Foundation, 20200722), and the institution he is currently employed at (Uppsala University Hospital). L.H.-M. receives research grants from the Spanish Ministry of Science and Innovation (PID2020-116927RB-C21) and Fondo Europeo de Desarrollo Regional (FEDER). D.K. receives consulting fees/honoraria from Bayer, Amomed, and Protherics Medicines Development. He receives research grants from the National Institute for Health Research (NIHR CDF-2015-08-074 RAE-AF; NIHR130280 DaRe2THINK; NIHR13274 D2T-NeuroVascular; and NIHR203326 Biomedical Research Centre), the British Heart Foundation (PG/17/55/33087, AA/182/3218, and FS/CDRF/21/21032), the EU/EFPIA Innovative Medicines Initiative (BigData@Heart 116074), EU Horizon and UKRI (HYPERMARKER 101095480) UK National Health Service—Data for R&D-Subnational Secure Data Environment programme, UK Department for Business, Energy Industrial Strategy Regulators Pioneer Fund, the Cook & Wolstenholme Charitable Trust, and the European Society of Cardiology supported by educational grants from Boehringer Ingelheim, BMS/Pfizer, Alliance, Bayer, Daiichi Sankyo, Boston Scientific, the NIHR/University of Oxford Biomedical Research Centre, and the British Hear Foundation, the University of Birmingham Accelerator Award (STEEER-AF). J.L.M. receives consulting fees/honoraria from Biotronik, Medtronic, MicroPort, and Milestone Pharmaceuticals. A.M. receives consulting fees/honoraria from Medtronic, Biosense Webster, and Boston Scientific and lecture fees from Medtronic, Boston Scientific, Biosense Webster, BMS, and Bayer. L.M. receives consulting fees/honoraria from Abbott, Medtronic, Boston Scientific, and Johnson & Johnson. G.A.N. receives lecture fees from AliveCor, consultant fees from Biosense Webster, and research grants from Abbott and Biosense Webster. H.P. receives consulting fees/honoraria from Abbott, Boston Scientific, Biosense Webster, Medtronic, Daiichi Sankyo, Bayer, and Pfizer. P.S. receives consulting fees/honoraria from Medtronic, Boston Scientific, Abbott, CathRx, and PaceMate (paid to the institution of employment). He is currently employed at the University of Adelaide, which receives research grants from Medtronic, Boston Scientific, and Becton-Dickenson. R.B.S. receives consulting fees/honoraria from BMS/Pfizer. She was partially supported by the European Union Horizon 2020 research and innovation programme (grant agreement 648131 and 847770), German Center for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK, grant numbers 81Z1710103 and 81Z0710114), German Ministry of Research and Education (BMBF 01ZX1408A), ERACoSysMed3 (031L0239), Wolfgang Seefried project funding German Heart Foundation. U.S. receives consulting fees/honoraria from University Svizzerra Italiana, Stanford, and Johnson & Johnson and research grants from the European Union, Dutch Heart Foundation, Roche, and EP Solution. He is a shareholder of YourRhythmics B.V. T.T. receives consulting fees/honoraria from Boston Scientific and Medtronic. I.C.v.G. receives consulting fees/honoraria from Bayer (paid to the institution of employment). She is currently employed at the University of Groningen. K.V. receives consulting fees/honoraria from Abbott, Philips, Medtronic, Biosense Webster, and Boston Scientific and research grants from Medtronic and Biosense Webster. R.W. receives consulting fees/honoraria from Boehringer Ingelheim, BMS/Pfizer, Daiichi Sankyo, Boston Scientific, Biotronik, Abiomed, and Zoll and a research grant from Boston Scientific, BMS/Pfizer, and Abiomed. S.W. receives consulting fees/honoraria from Boehringer Ingelheim, Boston Scientific, Abbott, and Bayer Vital and a research grant from Boston Scientific. All remaining authors (G.B., J.C.N., T.D.P., N.D., M.F., E.G., S.H., S.K., D.L., K.M.-R., M.O., A.S.P., U.R., M.R., D.S., C.S., G.S., D.S., S.T., R.H.v.L., and S.Z.) have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular., Competing Interests: Conflict of interest: C.B.: none declared. R.B.: personal fees from Bayer, Bristol-Myers Squibb, LEO-Pharma, Pfizer, VIATRIS, and research support by the Bavarian State Ministry of Health; CPC University of Colorado; FADOI, Italy. S.Be.: proctor and speaker fees from Boston Scientific, Edwards, Abbott, fees go to the department. S.Bi.: none declared. L.V.A.B.: consultant for Medtronic, Boston Scientific, Adagio, and ACUTUS, fees go to the department. G.B.: speaker fees from Bayer, Boehringer Ingelheim, Boston Scientific, Daiichi-Sankyo, Janssen, and Sanofi. S.Bo.: Consultant for Medtronic, Boston Scientific, Microport, and Zoll. A.J.C.: personal fees from Abbott, Boston Scientific, Medtronic, Pfizer/BMS, Daiichi Sankyo, Bayer and Sanofi. T.D.P.: no personal disclosures to report. Consultancy activity for Boston Scientific, invoiced through institutional research fund. W.D.: consulting and speaker fees from Ai Mediq, Bayer, Boehringer Ingelheim, Medtronic, Boston Scientific, Vifor Pharma; travel support from Pharmacosmos; research support from EU (Horizon2020), German Ministry of Education and Research, German Center for Cardiovascular Research, Vifor Pharma. S.G.: consulting and speaker fees from Boston Scientific. M.G.: Advisory Board Member for Boston Scientific; proctor for Boston Scientific, Abbott; fees for lectures and travel grants: from Boston Scientific, Abbott, Occlutech, Pfizer. K.G.H.: speaker’s honoraria, consulting fees, lecture honoraria and/or study grants from Abbott, Amarin; Alexion, AstraZeneca, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi-Sankyo, Edwards Lifesciences, Medtronic, Novartis, Pfizer, Portola, Premier Research, Sanofi, SUN Pharma, and W.L. Gore and Associates. J.E.N.-K.: consultant to Boston Scientific, Medtronic, Edwards Lifesciences, Picardia, Venus Medtech, speaker for Abbott. U.L.: research grant to institution from Abbott, Bayer, speaker or consulting honorary from Abbott, Boston Scientific, Bayer; Pfizer, Daiichi-Sankyo. G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multi-morbidity in AF, funded from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 899871. J.E.N.-K.: research grants from Abbott, Boston Scientific, Novo Nordic Foundation. J.E.N.-K.: research grants from Abbott, Boston Scientific, Novo Nordic Foundation. E.M.: research grants from Abbott, Biotronik, Boston Scientific, Medtronic, MicroPort, and Zoll. Consultant and speaker fees from Abbott, Abbott, Medtronic, and Zoll. J.E.N.-K.: research grants from Abbott, Boston Scientific, Novo Nordic Foundation. P.O.: speaking honoraria from Bayer, Abbott, Boston Scientific. T.P.: none declared. B.S.: consultant and speaker for Bostin Scientific, Abbott, Medtronic, Biosense Webster. M.S.: none declared. R.B.S. 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.) (81Z1710103 and 81Z0710114); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239); Wolfgang Seefried project funding German Heart Foundation; lecture fees and advisory board fees from BMS/Pfizer and Novartis outside this work. C.T.: advisory board member of Boston Scientific; proctor for Boston Scientific and Abbott; fees for lectures and travel grants from Boston Scientific and Abbott. A portion of the fees goes to the institute. A.T.: consultant and proctor for Abbott, consultant for Boston Scientific and Pie Medical., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear., Methods: We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212)., Results: From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I 2 statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I 2 =0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I 2 =0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I 2 =0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence)., Conclusions: The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding., Competing Interests: Disclosures All authors are either NOAH-AFNET 6 or ARTESiA investigators.

Background and Aims: Patients with long atrial high-rate episodes (AHREs) ≥24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients., Methods: This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation., Results: Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE ≥24 h were present at baseline in 259/2389 patients (11%, 78 ± 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE ≥24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE ≥24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001)., Conclusions: This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Oral anticoagulants (OAC) are underutilized in older patients with atrial fibrillation, despite proven clinical benefits. Our objective was to investigate baseline characteristics, treatment patterns, and impact of anticoagulation upon clinical outcomes with respect to age., Methods: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed up for 24 months. Adjusted hazard ratios (HR) were obtained via Cox proportional-hazards models with applied weights, to quantify the association of age with clinical outcomes. Comparative effectiveness of OAC vs No OAC and non-vitamin K oral anticoagulants (NOAC) vs vitamin K antagonists (VKA) were assessed using a propensity score with an overlap weighting scheme., Results: Of 52,018 patients, 32.6% were 65-74 years of age, 29.3% were 75-84 years, and 7.9% were ≥85 years. OAC treatment was associated with a numerical reduction in all-cause mortality among those aged 65-74 years (HR; 95% confidence interval) (0.86; 0.69-1.06) and aged 75-84 years (0.89; 0.75-1.05) and a significant reduction in patients ≥85 years (0.77; 0.63-0.95) vs no OAC. Similarly, OACs were associated with a decrease in stroke: 65-74 (0.51; 0.35-0.76) and ≥85 years (0.58; 0.34-0.99) and a numerical decrease in 75-84 years (0.84; 0.59-1.18). No increase in major bleeding was observed in patients aged ≥85 treated with OACs. Compared with VKA, NOACs were associated with a significant reduction in all-cause mortality in patients aged <65 and 65-74, with numerical reductions in those aged 75-84 and ≥85 years., Conclusions: Older patients using OACs saw lower all-cause mortality and stroke risk; NOACs had less mortality and major bleeding compared with VKAs., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subclinical atrial fibrillation is short-lasting and asymptomatic and can usually be detected only by long-term continuous monitoring with pacemakers or defibrillators. Subclinical atrial fibrillation is associated with an increased risk of stroke by a factor of 2.5; however, treatment with oral anticoagulation is of uncertain benefit., Methods: We conducted a trial involving patients with subclinical atrial fibrillation lasting 6 minutes to 24 hours. Patients were randomly assigned in a double-blind, double-dummy design to receive apixaban at a dose of 5 mg twice daily (2.5 mg twice daily when indicated) or aspirin at a dose of 81 mg daily. The trial medication was discontinued and anticoagulation started if subclinical atrial fibrillation lasting more than 24 hours or clinical atrial fibrillation developed. The primary efficacy outcome, stroke or systemic embolism, was assessed in the intention-to-treat population (all the patients who had undergone randomization); the primary safety outcome, major bleeding, was assessed in the on-treatment population (all the patients who had undergone randomization and received at least one dose of the assigned trial drug, with follow-up censored 5 days after permanent discontinuation of trial medication for any reason)., Results: We included 4012 patients with a mean (±SD) age of 76.8±7.6 years and a mean CHA 2 DS 2 -VASc score of 3.9±1.1 (scores range from 0 to 9, with higher scores indicating a higher risk of stroke); 36.1% of the patients were women. After a mean follow-up of 3.5±1.8 years, stroke or systemic embolism occurred in 55 patients in the apixaban group (0.78% per patient-year) and in 86 patients in the aspirin group (1.24% per patient-year) (hazard ratio, 0.63; 95% confidence interval [CI], 0.45 to 0.88; P = 0.007). In the on-treatment population, the rate of major bleeding was 1.71% per patient-year in the apixaban group and 0.94% per patient-year in the aspirin group (hazard ratio, 1.80; 95% CI, 1.26 to 2.57; P = 0.001). Fatal bleeding occurred in 5 patients in the apixaban group and 8 patients in the aspirin group., Conclusions: Among patients with subclinical atrial fibrillation, apixaban resulted in a lower risk of stroke or systemic embolism than aspirin but a higher risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; ARTESIA ClinicalTrials.gov number, NCT01938248.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Many patients with atrial fibrillation suffer from comorbid vascular disease. The comparative efficacy and safety of different types of oral anticoagulation (OAC) in this patient group have not been widely studied., Methods: Adults with newly diagnosed atrial fibrillation were recruited into the prospective observational registry, GARFIELD-AF, and followed for 24 months. Associations of vascular disease with clinical outcomes were analyzed using adjusted hazard ratios (HR) obtained via Cox proportional-hazard modeling. Outcomes of OAC vs no OAC, and of non-vitamin K antagonist OAC (NOAC) vs vitamin K antagonist (VKA) treatment, were compared by overlap propensity-weighted Cox proportional-hazard models., Results: Of 51,574 atrial fibrillation patients, 25.9% had vascular disease. Among eligible atrial fibrillation patients, those with vascular disease received OAC less frequently than those without (63% vs 73%). Over 2-year follow-up, patients with vascular disease showed a higher risk of all-cause mortality (HR 1.30; 95% confidence interval [CI], 1.16-1.47) and cardiovascular mortality (HR 1.59; 95% CI, 1.28-1.97). OAC was associated with a significant decrease in all-cause mortality and non-hemorrhagic stroke, and increased risk of major bleeding in non-vascular disease. In vascular disease, similar but non-significant trends existed for stroke and major bleeding. A significantly lower risk of all-cause mortality (HR 0.74; 95% CI, 0.61-0.90) and major bleeding (HR 0.45; 95% CI, 0.29-0.70) was observed in vascular disease patients treated with NOACs, compared with VKAs., Conclusions: Atrial fibrillation patients with a history of vascular disease have worse long-term outcomes than those without. The association of NOACs vs VKA with clinical outcomes was more evident in atrial fibrillation patients with vascular disease., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Reports of outcomes after atrial fibrillation (AF) diagnosis are conflicting. The aim of this study was to investigate mortality and hospitalization rates following AF diagnosis over time, by cause and by patient features., Methods: Individuals aged ≥16 years with a first diagnosis of AF were identified from the UK Clinical Practice Research Datalink-GOLD dataset from 1 January 2001, to 31 December 2017. The primary outcomes were all-cause and cause-specific mortality and hospitalization at 1 year following diagnosis. Poisson regression was used to calculate rate ratios (RRs) for mortality and incidence RRs (IRRs) for hospitalization and 95% confidence intervals (CIs) comparing 2001/02 and 2016/17, adjusted for age, sex, region, socio-economic status, and 18 major comorbidities., Results: Of 72 412 participants, mean (standard deviation) age was 75.6 (12.4) years, and 44 762 (61.8%) had ≥3 comorbidities. All-cause mortality declined (RR 2016/17 vs. 2001/02 0.72; 95% CI 0.65-0.80), with large declines for cardiovascular (RR 0.46; 95% CI 0.37-0.58) and cerebrovascular mortality (RR 0.41; 95% CI 0.29-0.60) but not for non-cardio/cerebrovascular causes of death (RR 0.91; 95% CI 0.80-1.04). In 2016/17, deaths caused from dementia (67, 8.0%), outstripped deaths from acute myocardial infarction, heart failure, and acute stroke combined (56, 6.7%, P < .001). Overall hospitalization rates increased (IRR 2016/17 vs. 2001/02 1.17; 95% CI, 1.13-1.22), especially for non-cardio/cerebrovascular causes (IRR 1.42; 95% CI 1.39-1.45). Older, more deprived, and hospital-diagnosed AF patients experienced higher event rates., Conclusions: After AF diagnosis, cardio/cerebrovascular mortality and hospitalization has declined, whilst hospitalization for non-cardio/cerebrovascular disease has increased., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy., Study Design: A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding., Conclusions: This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF., Clinical Trial Registration: NCT04394546., Competing Interests: Disclosures Dr Kar is a consultant to BSC, Abbott Vascular, Medtronic, LAMINAR, V-wave, Intershunt Highlife, co-principal investigator of the CHAMPION AF and REPAIR-MR studies and a steering committee member for the Triluminate and RELIEVE HF trials. Dr Doshi serves as a consultant to BSC, Biosense Webster, Abbott Vascular, Conformal and is co-principal investigator of the CHAMPION AF study. Dr Alkhouli is on the advisory board for BSC and received institutional research grant from BSC. Dr Camm received personal fees from Anthos, Menarini, Bayer, Daiichi Sankyo, Pfizer, Abbott and BSC. Dr Coylewright received research funding from BSC and Edwards Life Sciences and is a consultant for BSC, Edwards Life Sciences, Occlutech and Medtronic. Dr Gibson received research grant support payable to his institution and consulting fees from J&J, BMS, Diachi Sankyo, CeleCor and Merck. Dr Granger receives consulting fees from Abbvie, Abiomed, Alnylam Pharmaceuticals, Anthos, Bayer Corporation, Boehringer Ingelheim, BSC, Bristol Myers Squibb, Cardionomics, CeleCor Therapeutics, Janssen Pharmaceutical, Medscape, LLC, Medtronic, Inc., Merck, Nation Institutes of Health, Novo Nordisk, Novartis Pharmaceutical Company, PLX Pharma, Pfizer, Philips, REATA and NephroSynergy. He has an equity in Tenac.io. and salary funded by Duke grants sponsored by Boehinger Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, FDA, Janssen Pharmaceuticals, Novartis Pharmaceutical Company, Pfizer, and Philips. Dr Gurol received research funding from NIH and the hospital he is affiliated to received research funding from AVID, Pfizer and BSC. Dr Huber is on the Watchman Advisory Board. Dr Mansour is a consultant: for BSC. Dr Nair is an advisory board member and consultant for, and received research grant support from Biosense Webster, BSC, Abbott and Medtronic. Dr Natale is a consultant for Abbott, Baylis, Biosense Webster, BSC, Biotronik and Medtronic. Dr Pocock is a consultant for BSC. Dr Reddy serves as a consultant to, and has received grant support from, BSC. He reports additional disclosures unrelated to this manuscript: Consultant for and has equity in Ablacon, Acutus Medical, Affera, Medtronic, Apama Medical, Anumana, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Farapulse, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; Consultant for AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardiofocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, Pulse Biosciences; Equity in Manual Surgical Sciences, Newpace, Nyra Medical, Surecor, and Vizaramed. Dr Saliba is on the advisory board for BSC. Dr Christen and Allocco are full-time employees with an equity interest in BSC. Dr Ellenbogen received research support/lecture fees/honorarium and is a consultant for BSC. Dr Leon received clinical research grants to Columbia University from Abiomed-J&J, Abbott, BSC, Edwards and Medtronic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: This study aims to describe both management and prognosis of patients with diabetes mellitus (DM) and newly diagnosed atrial fibrillation (AF), overall as well as by antidiabetic treatment, and to assess the influence of oral anticoagulation (OAC) on outcomes by DM status., Methods: The study population comprised 52 010 newly diagnosed patients with AF, 11 542 DM and 40 468 non-DM, enrolled in the GARFIELD-AF registry. Follow-up was truncated at 2 years after enrolment. Comparative effectiveness of OAC versus no OAC was assessed by DM status using a propensity score overlap weighting scheme and weights were applied to Cox models., Results: Patients with DM [39.3% oral antidiabetic drug (OAD), 13.4% insulin ± OAD, 47.2% on no antidiabetic drug] had higher risk profile, OAC use, and rates of clinical outcomes compared with patients without DM. OAC use was associated in patients without DM and patients with DM with lower risk of all-cause mortality [hazard ratio 0.75 (0.69-0.83), 0.74 (0.64-0.86), respectively] and stroke/systemic embolism (SE) [0.69 (0.58-0.83), 0.70 (0.53-0.93), respectively]. The risk of major bleeding with OAC was similarly increased in patients without DM and those with DM [1.40 (1.14-1.71), 1.37 (0.99-1.89), respectively]. Patients with insulin-requiring DM had a higher risk of all-cause mortality and stroke/SE [1.91 (1.63-2.24)], [1.57 (1.06-2.35), respectively] compared with patients without DM, and experienced significant risk reductions of all-cause mortality and stroke/SE with OAC [0.73 (0.53-0.99); 0.50 (0.26-0.97), respectively]., Conclusions: In both patients with DM and patients without DM with AF, OAC was associated with lower risk of all-cause mortality and stroke/SE. Patients with insulin-requiring DM derived significant benefit from OAC., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Stroke prevention in patients with atrial fibrillation (AF) is one pillar of the management of this common arrhythmia. Substantial advances in the epidemiology and associated pathophysiology underlying AF-related stroke and thrombo-embolism are evident. Furthermore, the introduction of the non-vitamin K antagonist oral anticoagulants (also called direct oral anticoagulants) has clearly changed our approach to stroke prevention in AF, such that the default should be to offer oral anticoagulation for stroke prevention, unless the patient is at low risk. A strategy of early rhythm control is also beneficial in reducing strokes in selected patients with recent onset AF, when compared to rate control. Cardiovascular risk factor management, with optimization of comorbidities and attention to lifestyle factors, and the patient's psychological morbidity are also essential. Finally, in selected patients with absolute contraindications to long-term oral anticoagulation, left atrial appendage occlusion or exclusion may be considered. The aim of this state-of-the-art review article is to provide an overview of the current status of AF-related stroke and prevention strategies. A holistic or integrated care approach to AF management is recommended to minimize the risk of stroke in patients with AF, based on the evidence-based Atrial fibrillation Better Care (ABC) pathway, as follows: A: Avoid stroke with Anticoagulation; B: Better patient-centred, symptom-directed decisions on rate or rhythm control; C: Cardiovascular risk factor and comorbidity optimization, including lifestyle changes., Competing Interests: Conflict of interest: G.Y.H.L.: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees are received personally. M.P.: National leader of the AFFIRMO project on multi-morbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871; M.M.: Consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens Novartis, Janssen, Boehringer Ingelheim, Pfizer, and Sentreheart/Atricure and has equity in EPD-Philips (divested) and NewPace Ltd. T.P. and I.S.: None. H.F.T.: Consultant and speaker fee and research grant from for Abbott, BMS/Pfizer; Bayer; Boehringer Ingelheim; Boston Scientific, Daiichi-Sankyo; Medtronic and Sanofi. A.G.: EU Grant Horizon 2020 MAESTRIA Consortium; grant number 965286. Speaker fees from Abbott, Astra Zeneca, Bayer Health Care, Berlin Chemie, Biotronik, Boehringer Ingelheim, BMS/Pfizer, Boston Scientific, Daiichi-Sankyo, Medtronic, Omeicos, and Sanofi-Aventis. A.J.C.: Personal fees from Sanofi, Abbott, Boston Scientific, and Medtronic; Bayer, Daiichi Sankyo, Pfizer/BMS, Anthos, Menarini, Acesion, InCarda, Milestone, Arca, and Johnson and Johnson. C.B.-L.: Speaker’s and consultant’s fees from Bayer, Medtronic, CathPrint, Organon, Sanofi Aventis, Boston Sci, Jonson& Jonson, Abbotts, and Philips. D.G.: PI for institutional research grants from Boston Scientific and Medtronic. G.B.: Speaker’s fees of small amount from Bayer, Boehringer, Boston, Daiichi-Sankyo, Janssen, and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Atrial fibrillation (AF) is associated with life-threatening thromboembolism. Most emboli stem from thrombosis in the left atrial appendage (LAA). The current treatment of choice is oral anticoagulants (OACs), but a small proportion of patients cannot take OACs predominantly because of the so-called unacceptable bleeding risks. However, many who initially accept OACs subsequently stop therapy or reduce the OAC treatment to a potentially non-effective dose leaving them exposed to thromboembolic risk. A relatively simple alternative therapy involves the catheter-based insertion of a LAA closure (LAAC) device to prevent thromboembolism from the LAA. There is a considerable evidence base for this therapy consisting of clinical trials and observational data which suggests comparable therapeutic efficacy with a possible small excess of ischaemic strokes. Although LAAC has been very closely examined by regulators and approved for market release, guidelines from most professional societies give only weak recommendations for use of this device which may be the only known effective therapy available to some at-risk AF patients. Guidance materials from the same societies more enthusiastically endorse LAAC. Clinical practice is running well ahead of the guidelines because equipoise has been lost by physicians faced with patients for whom they have no other effective therapy. Guideline writers are correct in providing recommendations which are less strong for LAAC than for OACs, for those who are able and willing to take OAC treatment, but for those who are not, a stronger recommendation is needed. But, should the guidelines lag behind or leap ahead of the available evidence?, Competing Interests: Conflicts of interest: A.J.C. has received institutional grants and personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer Alliance, Daiichi Sankyo, Menarini, Abbott, and Boston Scientific., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care., Methods and Results: This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer's perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (-€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively., Conclusion: From a German healthcare payer's perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted., Competing Interests: Conflict of interest: H.JGM.C. reports support to institution from Medtronic, Cardialysis, Acesion Pharma, and InCarda Therapeutics and fees from Roche Diagnostics, Daiichi-Sankyo, and Sanofi, all outside the submitted work. P.V. receives consultant fees from Hygeia Hospitals Group, HHG, Servier International, and European Society of Cardiology. AJ.C. reports personal fees from Bayer, Daiichi Sankyo, Menarini, Pfizer, Sanofi, Medtronic, Abbott, and Boston Scientific. K.W. reports support to institution from the German Federal Ministry for Education and Research (BMBF), Atrial Fibrillation NETwork (AFNET), German Centre for Cardiovascular Researcher, EU Horizon 2020, and Biotronik and personal fees from Biotronik, Boston Scientific, and Novartis, all outside the submitted work. A.R. received consultant fees from Medtronic, KODEX-EPD, and Biosense Webster and travel grants and lecture fees from Medtronic, Cardiofocus, Biosense Webster, Abbott, Boehringer Ingelheim, Philips KODEX-EPD, Ablamap, Bayer, and Novartis. P.K. receives research support for basic, translational, and clinical research projects from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), and German Centre for Cardiovascular Research and 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 3 years. He is listed as inventor on two patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The safety and feasibility of combining percutaneous catheter ablation (CA) for atrial fibrillation with left atrial appendage occlusion (LAAO) as a single procedure in the USA have not been investigated. We analyzed the US National Readmission Database (NRD) to investigate the incidence of combined LAAO + CA and compare major adverse cardiovascular events (MACEs) with matched LAAO-only and CA-only patients., Methods and Results: In this retrospective study from NRD data, we identified patients undergoing combined LAAO and CA procedures on the same day in the USA from 2016 to 2019. A 1:1 propensity score match was performed to identify patients undergoing LAAO-only and CA-only procedures. The number of LAAO + CA procedures increased from 28 (2016) to 119 (2019). LAAO + CA patients (n = 375, mean age 74 ± 9.2 years, 53.4% were males) had non-significant higher MACE (8.1%) when compared with LAAO-only (n = 407, 5.3%) or CA-only patients (n = 406, 7.4%), which was primarily driven by higher rate of pericardial effusion (4.3%). All-cause 30-day readmission rates among LAAO + CA patients (10.7%) were similar when compared with LAAO-only (12.7%) or CA-only (17.5%) patients. The most frequent primary reason for readmissions among LAAO + CA and LAAO-only cohorts was heart failure (24.6 and 31.5%, respectively), while among the CA-only cohort, it was paroxysmal atrial fibrillation (25.7%)., Conclusion: We report an 63% annual growth (from 28 procedures) in combined LAAO and CA procedures in the USA. There were no significant difference in MACE and all-cause 30-day readmission rates among LAAO + CA patients compared with matched LAAO-only or CA-only patients., Competing Interests: Conflict of interest: J.C.H. has received honoraria from Medtronic, Abbott, Boston Scientific, Biotronik, Bristol-Myers Squibb, Pfizer, Janssen Pharmaceuticals, Zoll Medical, and Biosense-Webster, research grants from Biotronik and Biosense-Webster and has an equity interest in Acutus Medical and Vektor Medical. J.C. personal fees from Acesion, Allergan, Alta Thera, Arca, Incarda, Menarini, Milestone, Sanofi, Bayer, Daiichi Sankyo, Pfizer, Abbott, Biosense Webster, Biotronik, Boston Scientific, Lilly, Medtronic, and Johnson and Johnson. All the other authors have no disclosures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.)

The technological evolution and widespread availability of wearables and handheld ECG devices capable of screening for atrial fibrillation (AF), and their promotion directly to consumers, has focused attention of health care professionals and patient organizations on consumer-led AF screening. In this Frontiers review, members of the AF-SCREEN International Collaboration provide a critical appraisal of this rapidly evolving field to increase awareness of the complexities and uncertainties surrounding consumer-led AF screening. Although there are numerous commercially available devices directly marketed to consumers for AF monitoring and identification of unrecognized AF, health care professional-led randomized controlled studies using multiple ECG recordings or continuous ECG monitoring to detect AF have failed to demonstrate a significant reduction in stroke. Although it remains uncertain if consumer-led AF screening reduces stroke, it could increase early diagnosis of AF and facilitate an integrated approach, including appropriate anticoagulation, rate or rhythm management, and risk factor modification to reduce complications. Companies marketing AF screening devices should report the accuracy and performance of their products in high- and low-risk populations and avoid claims about clinical outcomes unless improvement is demonstrated in randomized clinical trials. Generally, the diagnostic yield of AF screening increases with the number, duration, and temporal dispersion of screening sessions, but the prognostic importance may be less than for AF detected by single-time point screening, which is largely permanent, persistent, or high-burden paroxysmal AF. Consumer-initiated ECG recordings suggesting possible AF always require confirmation by a health care professional experienced in ECG reading, whereas suspicion of AF on the basis of photoplethysmography must be confirmed with an ECG. Consumer-led AF screening is unlikely to be cost-effective for stroke prevention in the predominantly young, early adopters of this technology. Studies in older people at higher stroke risk are required to demonstrate both effectiveness and cost-effectiveness. The direct interaction between companies and consumers creates new regulatory gaps in relation to data privacy and the registration of consumer apps and devices. Although several barriers for optimal use of consumer-led screening exist, results of large, ongoing trials, powered to detect clinical outcomes, are required before health care professionals should support widespread adoption of consumer-led AF screening.

Background: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial-Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known., Methods: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA 2 DS 2 -VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA 2 DS 2 -VA score)., Results: EAST-AFNET4 randomized 1093 patients with CHA 2 DS 2 -VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA 2 DS 2 -VASc score <4 (67.4±8.0 years, 37% female). ERC reduced the composite primary efficacy outcome of cardiovascular death, stroke, or hospitalization for worsening of heart failure or for acute coronary syndrome in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51-0.81]; P < 0.001) but not in patients with CHA 2 DS 2 -VASc score <4 (ERC, 122/846 patients with events; UC, 133/850 patients with events; HR, 0.93 [0.73-1.19]; P =0.56, P =0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA interaction =0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P =0.175), but occurred more often in patients with CHA 2 DS 2 -VASc scores <4 randomized to ERC (ERC, 119/846 patients with events; UC, 91/850 patients with events; HR, 1.39 [1.05-1.82]; P =0.019, P interaction =0.008). Life-threatening events or death were not different between groups (CHA 2 DS 2 -VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA 2 DS 2 -VASc scores <4, ERC, 75/846 patients with event, UC, 73/850 patients with event). When female sex was ignored for the creation of higher and lower risk groups (CHA 2 DS 2 -VA score), the P interaction was not significant for the primary efficacy outcome ( P =0.25), but remained significant ( P =0.044) for the primary safety outcome., Conclusions: Patients with recently diagnosed atrial fibrillation and CHA 2 DS 2 -VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/; Unique identifier: ISRCTN04708680.

It is well known that diabetes is a prominent risk factor for cardiovascular (CV) events. The level of CV risk depends on the type and duration of diabetes, age and additional co-morbidities. Diabetes is an independent risk factor for atrial fibrillation (AF) and is frequently observed in patients with AF, which further increases their risk of stroke associated with this cardiac arrhythmia. Nearly one third of patients with diabetes globally have CV disease (CVD). Additionally, co-morbid AF and coronary artery disease are more frequently observed in patients with diabetes than the general population, further increasing the already high CV risk of these patients. To protect against thromboembolic events in patients with diabetes and AF or established CVD, guidelines recommend optimal CV risk factor control, including oral anticoagulation treatment. However, patients with diabetes exist in a prothrombotic and inflammatory state. Greater clinical benefit may therefore be seen with the use of stronger antithrombotic agents or innovative drug combinations in high-risk patients with diabetes, such as those who have concomitant AF or established CVD. In this review, we discuss CV risk management strategies in patients with diabetes and concomitant vascular disease, stroke prevention regimens in patients with diabetes and AF and how worsening renal function in these patients may complicate these approaches. Accumulating evidence from clinical trials and real-world evidence show a benefit to the administration of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with diabetes and AF., (© 2022. The Author(s).)

Background: Whether atrial fibrillation (AF) pattern or timing of AF therapy modifies the effectiveness of early rhythm control (ERC) is not known., Objectives: This study sought to compare clinical characteristics and outcomes in patients presenting with different AF patterns on ERC vs usual care., Methods: The effects of ERC were compared in first-diagnosed AF (FDAF), paroxysmal AF (paroxAF), and persistent AF (persAF) in this prespecified analysis of the EAST-AFNET 4 (Early treatment of atrial fibrillation for stroke prevention) trial. Associations between AF pattern and primary outcomes (first primary outcome: cardiovascular death, stroke, and hospitalization for heart failure and acute coronary syndrome; second primary outcome: nights spent in hospital per year) were compared over a mean follow-up of 5.1 years. Changes in health-related quality of life were assessed by the EQ-5D., Results: FDAF patients (n = 1,048, enrolled 7 days after diagnosing AF) were slightly older (71 years of age, 48.0% female) than patients with paroxAF (n = 994, 70 years of age, 50.0% female) and persAF (n = 743, 70 years of age, 38.0% female). ERC reduced the primary outcome in all 3 AF patterns. Hospitalizations for acute coronary syndrome were highest in FDAF (incidence rate ratio [IRR]: 1.50; 95% CI: 0.83-2.69; P for interaction = 0.032) compared with paroxAF (IRR: 0.64; 95% CI: 0.32-1.25) and persAF (IRR: 0.50; 95% CI: 0.25-1.00). FDAF patients spent more nights in hospital (IRR: 1.38; 95% CI: 1.12-1.70; P for interaction = 0.004) than paroxAF (IRR: 0.84; 95% CI: 0.67-1.03), and persAF (IRR: 1.02; 95% CI: 0.80-1.30) patients. ERC improved health-related quality of life (EQ-5D score) in patients with paroxAF and persAF but not in patients with FDAF (P = 0.019)., Conclusions: ERC reduces the first primary composite outcome in all AF patterns. Patients with FDAF are at high risk for hospitalization and acute coronary syndrome, particularly on ERC. (Early treatment of atrial fibrillation for stroke prevention trial; ISRCTN04708680; Early Treatment of Atrial Fibrillation for Stroke Prevention Trial [EAST]; NCT01288352; Early treatment of Atrial fibrillation for Stroke prevention Trial [EAST]; EudraCT2010-021258-20)., Competing Interests: Funding Support and Author Disclosures Dr Goette was partially supported by the EU Horizon 2020 MAESTRIA Consortium (grant number 965286). Dr Kirchhof was partially supported by the EU BigData@Heart (grant agreement EU IMI 116074), AFFECT-AF (grant agreement 847770), and MAESTRIA (grant agreement 965286); the British Heart Foundation (PG/17/30/32961; PG/20/22/35093; AA/18/2/34218), the German Centre for Cardiovascular Research supported by the German Ministry of Education and Research, and the Leducq Foundation. The EAST-AFNET 4 trial was supported by AFNET, the European Heart Rhythm Association, the German Centre for Cardiovascular Research, the German Heart Foundation, Sanofi, and Abbott. Dr Goette has received speaker fees from Abbott, AstraZeneca, Bayer Health Care, Berlin Chemie, Biotronik, Boehringer Ingelheim, BMS/Pfizer, Boston Scientific, Daiichi-Sankyo, Medtronic, Omeicos, Sanofi, and Viofor. Dr Camm has served as an advisor for Bayer, Daiichi-Sankyo, Pfizer/BMS, Medtronic, Boston Scientific, Abbott, Menarini, and Sanofi. Dr Kuck has served as a consultant for CardioValve; and has received grant support from Medtronic and Biosense Webster. Dr Wegscheider has served as a lecturer and statistical consultant for Biotronik, Boston Scientific, and Novartis; and has received grant support from Biotronik and Resmed. Dr Kirchhof has received research support for basic, translational, and clinical research projects from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (United Kingdom), and German Centre for Cardiovascular Research and from several drug and device companies active in atrial fibrillation; has received honoraria from several such companies in the past, but not in the last 3 years; and has been listed as inventor on 2 patents held by University of Birmingham (Atrial Fibrillation Therapy WO 2015140571, Markers for Atrial Fibrillation WO 2016012783). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The considerable mortality and morbidity associated with atrial fibrillation (AF) pose a substantial burden on patients and health care services. Although the management of AF historically focused on decreasing AF recurrence, it evolved over time in favor of rate control. Recently, more emphasis has been placed on reducing adverse cardiovascular outcomes using rhythm control, generally by using safe and effective rhythm-control therapies (typically antiarrhythmic drugs and/or AF ablation). Evidence increasingly supports early rhythm control in patients with AF that has not become long-standing, but current clinical practice and guidelines do not yet fully reflect this change. Early rhythm control may effectively reduce irreversible atrial remodeling and prevent AF-related deaths, heart failure, and strokes in high-risk patients. It has the potential to halt progression and potentially save patients from years of symptomatic AF; therefore, it should be offered more widely., Competing Interests: Funding Support and Author Disclosures This work was supported by Sanofi for editorial assistance with article preparation only. Dr Camm has received consulting fees from Allergan, Arca, Acesion, Incarda, Menarini, Milestone, Sanofi, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Pfizer, Boston Scientific, Abbott, Biotronik, Medtronic, and Johnson and Johnson; and has received institutional grants from Bayer, Boehringer Ingelheim, Daichi-Sankyo, and Pfizer/Bristol Myers Squibb. Dr Naccarelli has received consultant fees from ARCA, Sanofi, Janssen, GlaxoSmithKline, Omeicos, Milestone, and Acesion. Dr Mittal has received consultant fees from Abbott, Baylis Medical, Boston Scientific, Medtronic, Philips, and Sanofi. Dr Crijns has received consultant/advisor/speaker fees from Acesion, Incarda, Sanofi, Roche, Ksyos, Corsano Health, and DZHK; has received support for educational activities from Medtronic, Abbott, and Boston Scientific; and has been supported by ZonMw (grant number 104021005 - RACE 9). Dr Hohnloser has received consulting fees from Bayer Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, Daiichi-Sankyo, Gilead, Johnson & Johnson, Medtronic, Pfizer, Sanofi, Servier, and Zoll; and has received lecture fees from Bayer Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer, Sanofi, and Medtronic. Dr Ma has received honoraria from Bristol Myers Squibb, Pfizer, Johnson & Johnson, Boehringer Ingelheim, and Bayer for giving lectures; no personal fees received. Dr Natale has been a consultant for Abbott, Baylis, Biosense Webster, Boston Scientific, Biotronik, and Medtronic. Dr Turakhia has received personal fees from Medtronic Inc, Abbott, Biotronik, Sanofi, Pfizer, Bayer, Myokardia, Johnson and Johnson, Milestone Pharmaceuticals, InCarda Pharmaceuticals, 100Plus, AliveCor, Acutus Medical, and BrightInsight; has received grants from Bristol Myers Squibb, the American Heart Association, Apple, Bayer, and the U.S. Food and Drug Administration; and is an editor for JAMA Cardiology. Dr Kirchof has received research support for basic, translational, and clinical research projects from European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), German Centre for Cardiovascular Research, and from several drug and device companies active in atrial fibrillation; has received honoraria from several such companies in the past, but not in the last 3 years; is listed on 2 patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571 and Markers for Atrial Fibrillation WO 2016012783); and has been partially supported by European Union BigData@Heart (grant agreement EU IMI 116074), AFFECT-AF (grant agreement 847770), and MAESTRIA (grant agreement 965286), British Heart Foundation (PG/17/30/32961 and PG/20/22/35093; AA/18/2/34218), German Centre for Cardiovascular Research supported by the German Ministry of Education and Research (DZHK), and Leducq Foundation., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4., Methods and Results: Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P < 0.001), mainly due to visits for symptomatic AF recurrences or recurrent AF on telemetric ECGs., Conclusion: The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control., Methods and Results: This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19)., Conclusion: The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To determine whether the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) integrated risk tool predicts mortality, non-haemorrhagic stroke/systemic embolism, and major bleeding for up to 2 years after new-onset AF and to assess how this risk tool performs compared with CHA2DS2-VASc and HAS-BLED., Methods and Results: Potential predictors of events included demographic and clinical characteristics, choice of treatment, and lifestyle factors. A Cox proportional hazards model was identified for each outcome by least absolute shrinkage and selection operator methods. Indices were evaluated in comparison with CHA2DS2-VASc and HAS-BLED risk predictors. Models were validated internally and externally in ORBIT-AF and Danish nationwide registries. Among the 52 080 patients enrolled in GARFIELD-AF, 52 032 had follow-up data. The GARFIELD-AF risk tool outperformed CHA2DS2-VASc for all-cause mortality in all cohorts. The GARFIELD-AF risk score was superior to CHA2DS2-VASc for non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in internal validation and in the Danish AF cohort. In very low- to low-risk patients [CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)], the GARFIELD-AF risk score offered strong discriminatory value for all the endpoints when compared to CHA2DS2-VASc and HAS-BLED. The GARFIELD-AF tool also included the effect of oral anticoagulation (OAC) therapy, thus allowing clinicians to compare the expected outcome of different anticoagulant treatment decisions [i.e. no OAC, non-vitamin K antagonist (VKA) oral anticoagulants, or VKAs]., Conclusions: The GARFIELD-AF risk tool outperformed CHA2DS2-VASc at predicting death and non-haemorrhagic stroke, and it outperformed HAS-BLED for major bleeding in overall as well as in very low- to low-risk group patients with AF., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF: NCT01090362, ORBIT-AF I: NCT01165710; ORBIT-AF II: NCT01701817., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: In patients with newly diagnosed atrial fibrillation (AF), do baseline risk factors and stroke prevention strategies account for the geographically diverse outcomes., Design: Global Anticoagulant Registry in the FIELD-Atrial Fibrillation is a prospective multinational non-interventional registry of patients with newly diagnosed AF (n=52 018 patients)., Setting: Investigator sites (n=1317) were representative of the care settings/locations in each of the 35 participating countries. Treatment decisions were all determined by the local responsible clinicians., Participants: The patients (18 years and over) with newly diagnosed AF had at least 1 investigator-determined stroke risk factor and patients were not required to meet specific thresholds of risk score for anticoagulant treatment., Main Outcomes and Measures: Observed 1-year event rates and risk-standardised rates were derived., Results: Rates of death, non-haemorrhagic stroke/systemic embolism and major bleeding varied more than three-to-four fold across countries even after adjustment for baseline factors and antithrombotic treatments. Rates of anticoagulation and antithrombotic treatment varied widely. Patients from countries with the highest rates of cardiovascular mortality and stroke were among the least likely to receive oral anticoagulants. Beyond anticoagulant treatment, variations in the treatment of comorbidities and lifestyle factors may have contributed to the variations in outcomes. Countries with the lowest healthcare Access and Quality indices (India, Ukraine, Argentina, Brazil) had the highest risk-standardised mortality., Conclusion: The variability in outcomes across countries for patients with newly diagnosed AF is not accounted for by baseline characteristics and antithrombotic treatments. Residual mortality rates were correlated with Healthcare Access and Quality indices. The findings suggest the management of patients with AF needs to not only address guideline indicated and sustained anticoagulation, but also the treatment of comorbidities and lifestyle factors., Trial Registration Number: NCT01090362., Competing Interests: Competing interests: KAAF has received grants and personal fees from Bayer/Janssen and AstraZeneca and personal fees from Sanofi/Regeneron and Verseon. AJC: Institutional grants and personal fees from Bayer, Boehringer Ingelheim, BMS/Pfizer and Daichi Sankyo; SG has received Personal fees from Thrombosis Research Institute and the American Heart Association, grants from Sanofi, Pfizer, Ono, Bristol Myer Squibb, the Vehicle Racing Commemorative Foundation and Nakatani Foundation for Advancement of Measuring Technologies in Biomedical Engineering. SZG has received research support from Boehringer-Ingelheim, BMS, BTG EKOS, Daiichi, Janssen, NHLBI, and the Thrombosis Research Institute; has served as a consultant for Agile, Bayer, Boehringer-Ingelheim, BMS, Daiichi, Janssen and Zafgen. SH has received personal fees from Aspen, Bayer Healthcare, BMS/Pfizer, Daiichi-Sankyo, and Sanofi. YK: Research grant from Daiichi Sankyo and Boeringer Ingelheim. Personal fees from: Daiichi Sankyo, Boehringer Ingelheim, Bayer, Bristol Meyers and Pfizer; FM is a former employee of Bayer AG. SO: consultant/advisory board payments from Bayer Pharma AG, Bristol-Myers Squibb Korea, Boehringer-Ingelheim Korea, Pfizer Korea, Sanofi-Aventis, and St Jude Medical. JPSS: Personal fee from Pfizer, Astra Zeneca, Novartis, Sanofi & BMS; JPP: Reported grants for clinical research from Abbott, American Heart Association, Boston Scientific, Gilead, Janssen Pharmaceuticals, NHLBI, and Philips and serves as a consultant to Abbott, Allergan, ARCA Biopharma, Biotronik, Boston Scientific, Johnson & Johnson, LivaNova, Medtronic, Milestone, Oliver Wyman Health, Sanofi, Philips, and Up-to-Date. JS: Research grants from Bayer; personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS/Pfizer, Novartis, Sanofi, Servier; Expert witness for Boehringer Ingelheim; AGGT has received personal fees from Bayer Healthcare, Janssen Pharmaceutical Research & Development, and Portola. FV has received grants from Bayer Healthcare; personal fees from Bayer Healthcare, BMS/Pfizer, DaiichiSankyo, and Boehringer-Ingelheim. AKK has received research support from Bayer AG and Sanofi; personal fees from Bayer AG, Pfizer, Janssen, Sanofi, Verseon and Anthos Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Atrial fibrillation (AF), type 2 diabetes mellitus (DM), and chronic kidney disease (CKD) are three global epidemics with significant effects on morbidity and mortality. Diabetes is a risk factor for AF, and a risk factor for thromboembolism, comorbidity, and mortality when AF is present. The pathophysiology of diabetes-related AF and interrelationships with cardiovascular events and renal events is not fully understood but is in part related to structural, electrical, electromechanical, and autonomic remodelling. The current practice guidelines offer limited recommendations on the management of patients with AF (or risk of AF) and diabetes with its own heterogeneity for the prevention of cardiovascular and renal events. This document discusses possible clinical approaches for these patients. In the last decade, there have been major improvements for the prevention of stroke in AF patients with direct oral anticoagulants, which are preferable to vitamin K antagonists for stroke prevention in DM. Because of the increased risk rate for several cardiovascular adverse events in diabetic patients, a similar relative risk reduction generally translates into greater absolute risk reduction in the diabetic population. Recent trials with non-insulin diabetes drugs using glucagon-like peptide-1 agonists and sodium-glucose cotransporter-2 inhibitors showed a significant reduction for the risk of major adverse cardiovascular events in patients with type 2 DM. Sodium-glucose cotransporter-2 inhibitors also showed a large reduction in hospitalization for heart failure and renal events, which need to be more completely evaluated in patients with AF. Mechanisms, risks, and optimal management of AF patients with DM who have or are under risk of developing heart failure or CKD are also discussed in this document. The benefits of medical therapies for these patients still need to be put into perspective, and gaps in evidence on some of these issues are likely to be addressed in future years., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: The objective was to evaluate the clinical characteristics, management and two-year outcomes of patients with newly diagnosed non-valvular atrial fibrillation at risk for stroke in Nordic countries., Methods: We examined the baseline characteristics, antithrombotic treatment, and two-year clinical outcomes of patients from four Nordic countries., Results: A total of 52,080 patients were enrolled in the GARFIELD-AF. Out of 29,908 European patients, 2,396 were recruited from Nordic countries. The use of oral anticoagulants, alone or in combination with antiplatelet (AP), was higher in Nordic patients in all CHA 2 DS 2 -VASc categories: 0-1 (72.8% vs 60.3%), 2-3 (78.7% vs 72.9%) and ≥4 (79.2% vs 74.1%). In Nordic patients, NOAC ± AP was more frequently prescribed (32.0% vs 27.7%) and AP monotherapy was less often prescribed (10.4% vs 18.2%) when compared with Non-Nordic European patients. The rates (per 100 patient years) of all-cause mortality and non-haemorrhagic stroke/systemic embolism (SE) were similar in Nordic and Non-Nordic European patients [3.63 (3.11-4.23) vs 4.08 (3.91-4.26), p value = .147] and [0.98 (0.73-1.32) vs 1.02 (0.93-1.11), p value = .819], while major bleeding was significantly higher [1.66 (1.32-2.09) vs 1.01 (0.93-1.10), p value < .001]., Conclusion: Nordic patients had significantly higher major bleeding than Non-Nordic-European patients. In contrast, rates of all-cause mortality and non-haemorrhagic stroke/SE were comparable., Clinical Trial Registration: Unique identifier: NCT01090362. URL: http://www.clinicaltrials.gov., Key Message: Nordic countries had significantly higher major bleeding than Non-Nordic-European countries. Rates of mortality and non-haemorrhagic stroke/SE were similar .

Atrial fibrillation is associated with a five-fold increase in the risk of stroke. Current guidelines recommend the use of the CHA2DS2-VASc score to stratify the risk of stroke. In addition, guidelines recommend the identification of the conditions that increase the risk of haemorrhage to be modified and thus decrease the risk of bleeding. Nevertheless, many patients with a high thromboembolic risk are prescribed antiplatelet treatment or do not receive any antithrombotic therapy. In addition, therapeutic inertia is common in anticoagulated patients taking vitamin K antagonists, and underdosing is an emerging problem with direct oral anticoagulants, probably because many physicians consider the risk of stroke and the risk of major bleeding to be equal. It is necessary to develop a new approach to risk stratification, an approach that moves from morbidity to mortality, i.e., from stratification of the risk of stroke and major bleeding to stratification of the risk of mortality associated with stroke and the risk of mortality associated with bleeding. In this article, we propose a novel risk stratification approach based on the mortality associated with stroke and bleeding, illustrated by data derived from the literature., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Multiple randomized controlled trials and many real-world evidence studies have consistently shown that non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to vitamin K antagonists for thromboembolic stroke prevention in the majority of patients with atrial fibrillation (AF). However, their role in the management of patients with AF and comorbidities, as well as in other patient populations with a high risk of stroke, such as patients with prior embolic stroke of undetermined source (ESUS) and those with atherosclerosis, is less clear. There is now increasing evidence suggesting that NOACs have a beneficial effect in the prevention of stroke in patients with AF and comorbidities, such as renal impairment and diabetes. In addition, while studies investigating the efficacy and safety of NOACs for the prevention of secondary stroke in patients with a history of ESUS demonstrated neutral results, subanalyses suggested potential benefits in certain subgroups of patients with ESUS. One NOAC, rivaroxaban, has also recently been found to be effective in reducing the risk of stroke in patients with chronic cardiovascular disease including coronary artery disease and peripheral artery disease, further broadening the patient groups that may benefit from NOACs. In this article, we will review recent evidence for the use of NOACs across the stroke spectrum in detail, and discuss the progress and future prospects in the different stroke areas., Competing Interests: A.J.C. has received institutional grants and personal fees from Bayer AG, Boehringer Ingelheim, BMS, Daiichi Sankyo, and Pfizer, and personal fees from Abbott and Boston Scientific.D.A. has received speaker and consultancy honoraria from Boehringer Ingelheim, BMS/Pfizer, MSD, Bayer Healthcare, and AstraZeneca, and research grants to the institution from Medtronic and BMS/Pfizer., (Thieme. All rights reserved.)

The RACE trial was one of the first landmark trials to establish whether restoring and maintaining sinus rhythm could reduce morbidity and mortality in patients with atrial fibrillation (AF). Its neutral outcome shaped clinical decision-making for almost 20 years. However, there were two important treatment-related factors associated with mortality of rhythm control therapy at that time: One was safety of antiarrhythmic drug therapy, and the other one withdrawal of anticoagulation after restoration of sinus rhythm. Both concerns have been overcome, and, moreover, important knowledge considering the importance of time for the treatment of AF has been gained. These insights led to the concept of the EAST-AFNET 4 trial, and after more than two decades in the pursuit of ongoing therapeutic improvement, early rhythm control therapy has demonstrated to reduce a composite of cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome, by 21% (first primary outcome, absolute reduction 1.1 per 100 patient-years). For this entire period, Harry Crijns characterized the treatment of AF patients, and contributed decisively to realizing the benefit of rhythm control therapy. It is almost easier to list the clinical trials without Harry's involvement than to list those which he co-designed and led., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Heart failure (HF) and atrial fibrillation (AF) may coexist and influence each other. However, characteristics, anticoagulant treatment, and outcomes of contemporary AF patients with concurrent HF are ill-defined. This study analyses characteristics, treatment, and 2 year outcomes in newly diagnosed Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) patients with vs. without HF., Methods and Results: GARFIELD-AF is the world's largest observational AF patient study. At enrolment, 11 758 of 52 072 patients (22.6%) had HF; 76.3% were New York Heart Association class II-III. Patients with HF had comparable demographics, blood pressure, and heart rate but more likely had permanent (15.6% vs. 11.9%) or persistent AF (18.9% vs. 13.8%), acute coronary syndromes (16.7% vs. 8.9%), vascular disease (40.8% vs. 20.2%), and moderate-to-severe chronic kidney disease (14.6% vs. 9.0%) than those without. Anticoagulant prescription was similar between the two groups. At 2 year follow-up, patients with HF showed a greater risk of all-cause mortality [hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.91-2.21; P < 0.0001], cardiovascular mortality (HR, 2.91; 95% CI, 2.58-3.29; P < 0.0001), acute coronary syndromes (HR, 1.25; 95% CI, 1.02-1.52; P = 0.03), and stroke/systemic embolism (HR, 1.24; 95% CI, 1.07-1.43; P = 0.0044). Major bleeding rate was comparable (adjusted HR, 1.00; 95% CI, 0.84-1.18; P = 0.968). Among patients without HF at baseline, incidence of new HF was low [0.69 (95% CI, 0.63-0.75) per 100 person-years], whereas propensity to develop worsening HF was higher in those with HF [1.62 (95% CI, 1.45-1.80) per 100 person-years]., Conclusions: Patients with AF and HF have a high risk of all-cause and cardiovascular mortality and stroke/systemic embolism and may develop worsening HF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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.)

The Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) examined real-world practice in a total of 57,149 (5069 retrospective, 52,080 prospective) patients with newly diagnosed AF at risk of stroke/systemic embolism, enrolled at over 1000 centers in 35 countries. It aimed to capture data on AF burden, patients' clinical profile, patterns of clinical practice and antithrombotic management, focusing on stroke/systemic embolism prevention, uptake of new oral anticoagulants, impact on death and bleeding. GARFIELD-AF set new standards for quality of data collection and analysis. A total of 36 peer-reviewed articles were already published and 73 abstracts presented at international congresses, covering treatment strategies, geographical variations in baseline risk and therapies, adverse outcomes and common comorbidities such as heart failure. A risk prediction tool as well as innovative observational studies and artificial intelligence methodologies are currently being developed by GARFIELD-AF researchers. Clinical Trial Registration: NCT01090362 (ClinicalTrials.gov).

Aims: To evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) with the Amplatzer™ Amulet™ occluder., Methods and Results: Patients with atrial fibrillation eligible for LAAO were recruited to a prospective global study. Implant procedures were undertaken with echocardiographic guidance. Transoesophageal echocardiography (TOE) was undertaken 1-3 months post-LAAO. Implant and follow-up TOEs were evaluated by a CoreLab. The primary endpoint was a composite of ischaemic stroke and cardiovascular death at 2 years. Serious adverse events were adjudicated by an independent clinical events committee. A total of 1088 patients were enrolled, aged 75.2 ± 8.5 years; 64.5% were male. CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.6 and 3.3 ± 1.1, respectively. A total of 71.7% had prior major bleeding, and 82.8% had contraindications to oral anticoagulants. Implant success was 99.1%. Major adverse events (≤7 days post-procedure) occurred in 4.0%, including death (0.3%), stroke (0.4%), major vascular (1.3%), and device embolization (0.2%). A total of 80.2% of patients were discharged on antiplatelet therapy alone. Peridevice flow was <3 mm in 98.4% at follow-up TOE. Device-related thrombus (DRT) was seen in 1.6% of cases. Cardiovascular death or ischaemic stroke occurred in 8.7% of patients at 2 years. The ischaemic stroke rate was 2.2%/year-a 67% reduction compared to the CHA2DS2-VASc predicted rate. Major bleeding (Bleeding Academic Research Consortium type ≥ 3) occurred at rates of 10.1%/year (year 1) and 4.0%/year (year 2)., Conclusion: Following LAAO with the Amplatzer Amulet device, the ischaemic stroke rate was reduced by 67% compared to the predicted risk. Closure was complete in 98.4% of cases and DRT seen in only 1.6%., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.

Background: It is not always possible to verify whether a patient complaining of symptoms consistent with transient ischemic attack has had an actual cerebrovascular event., Research Question: To characterize the risk of cardiovascular events associated with a history of stroke/transient ischemic attack in patients with atrial fibrillation., Study Design and Methods: This study investigated the clinical characteristics and outcomes of patients with a history of stroke/transient ischemic attack among 52,014 patients enrolled prospectively in GARFIELD-AF registry. The diagnosis of stroke or transient ischemic attack was not protocol defined but based on physicians' assessment. Patients' one-year risk of death, stroke/systemic embolism, and major bleeding was assessed by multivariable Cox regression., Results: At enrollment, 5617 (10.9%) patients were reported to have a history of stroke or transient ischemic attack. Patients with stroke or transient ischemic attack were older and had a greater burden of diabetes, moderate-to-severe kidney disease, and atherothrombosis and higher median CHA 2 DS 2 -VASc and HAS-BLED scores than those without history of stroke or transient ischemic attack. After adjustment, prior stroke/transient ischemic attack was associated with significantly higher risk for all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.12-1.42), cardiovascular death (HR, 1.22; 95% CI, 1.01-1.48), non-cardiovascular death (HR, 1.39; 95% CI, 1.15-1.68), and stroke/systemic embolism (HR, 2.17; 95% CI, 1.80-2.63) than patients without history of stroke/transient ischemic attack. In patients with a prior stroke alone higher risk was observed for all-cause mortality (HR, 1.29; 95% CI, 1.11-1.50), non-cardiovascular death (HR, 1.39; 95% CI, 1.10-1.77), and stroke/systemic embolism (HR, 2.29; 95% CI, 1.83-2.86). No significantly elevated risk of adverse events was seen for patients with history of transient ischemic attack alone., Interpretation: A history of prior stroke or transient ischemic attack is a strong independent risk factor for mortality and stroke/systemic embolism. This excess risk is mainly attributed to a history of stroke (with or without transient ischemic attack), whereas history of transient ischemic attack is a weaker predictor. Clinical trial registration: NCT01090362.

Background Reducing major bleeding events is a challenge when managing anticoagulation in patients with atrial fibrillation. This study evaluated the impact of modifiable and nonmodifiable bleeding risk factors in patients with atrial fibrillation receiving rivaroxaban and estimated the impact of risk factor modification on major bleeding events. Methods and Results Modifiable and nonmodifiable risk factors associated with major bleeding events were identified from the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) prospective registry data set (6784 rivaroxaban-treated patients). Parameters showing univariate association with bleeding were used to construct a multivariable model identifying independent risk factors. Modeling was used to estimate attributed weights to risk factors. Heavy alcohol use (hazard ratio [HR]=2.37; 95% CI 1.24-4.53); uncontrolled hypertension (HR after parameter-wise shrinkage=1.79; 95% CI 1.05-3.05); and concomitant treatment with antiplatelets, nonsteroidal anti-inflammatory drugs, or paracetamol (HR=1.80; 95% CI 1.24-2.61) were identified as modifiable, independent bleeding risk factors. Increasing age (HR=1.25 [per 5-year increment]; 95% CI 1.12-1.38); heart failure (HR=1.97; 95% CI 1.36-2.86); and vascular disease (HR=1.91; 95% CI 1.32-2.77) were identified as nonmodifiable bleeding risk factors. Overall, 128 (1.9%) patients experienced major bleeding events; of these, 11% had no identified bleeding risk factors, 50% had nonmodifiable bleeding risk factors only, and 39% had modifiable bleeding risk factors (with or without nonmodifiable risk factors). The presence of 1 modifiable bleeding risk factor doubled the risk of major bleeding. Conclusions Elimination of modifiable bleeding risk factors is a potentially effective strategy to reduce bleeding risk in atrial fibrillation patients receiving rivaroxaban. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01606995.

Aims: Guidelines do not recommend to take pattern of atrial fibrillation (AF) into account for the indication of anticoagulation (AC). We assessed AF pattern and the risk of cardiovascular events during 2-years of follow-up., Methods and Results: We categorized AF as paroxysmal, persistent, or permanent in 29 181 patients enrolled (2010-15) in the Global Anticoagulant Registry In the FIELD of AF (GARFIELD-AF). We used multivariable Cox regression to assess the risks of stroke/systemic embolism (SE) and death across patterns of AF, and whether this changed with AC on outcomes. Atrial fibrillation pattern was paroxysmal in 14 344 (49.2%), persistent in 8064 (27.6%), and permanent 6773 (23.2%) patients. Median CHA2DS2-VASc, GARFIELD-AF, and HAS-BLED scores assessing the risk of stroke/SE and/or bleeding were similar across AF patterns, but the risk of death, as assessed by the GARFIELD-AF risk calculator, was higher in non-paroxysmal than in paroxysmal AF patterns. During 2-year follow-up, after adjustment, non-paroxysmal AF patterns were associated with significantly higher rates of all-cause death, stroke/SE, and new/worsening congestive heart failure (CHF) than paroxysmal AF in non-anticoagulated patients only. In anticoagulated patients, a significantly higher risk of death but not of stroke/SE and new/worsening CHF persisted in non-paroxysmal compared with paroxysmal AF patterns., Conclusion: In non-anticoagulated patients, non-paroxysmal AF patterns were associated with higher risks of stroke/SE, new/worsening HF and death than paroxysmal AF. In anticoagulated patients, the risk of stroke/SE and new/worsening HF was similar across all AF patterns. Thus AF pattern is no longer prognostic for stroke/SE when patients are treated with anticoagulants., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To externally validate the accuracy of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) model against existing risk scores for stroke and major bleeding risk in patients with non-valvular AF in a population-based cohort., Design: Retrospective cohort study., Setting: Danish nationwide registries., Participants: 90 693 patients with newly diagnosed non-valvular AF were included between 2010 and 2016, with follow-up censored at 1 year., Primary and Secondary Outcome Measures: External validation was performed using discrimination and calibration plots. C-statistics were compared with CHA 2 DS 2 VASc score for ischaemic stroke/systemic embolism (SE) and HAS-BLED score for major bleeding/haemorrhagic stroke outcomes., Results: Of the 90 693 included, 51 180 patients received oral anticoagulants (OAC). Overall median age (Q1, Q3) were 75 (66-83) years and 48 486 (53.5%) were male. At 1-year follow-up, a total of 2094 (2.3%) strokes/SE, 2642 (2.9%) major bleedings and 10 915 (12.0%) deaths occurred. The GARFIELD-AF model was well calibrated with the predicted risk for stroke/SE and major bleeding. The discriminatory value of GARFIELD-AF risk model was superior to CHA 2 DS 2 VASc for predicting stroke in the overall cohort (C-index: 0.71, 95% CI: 0.70 to 0.72 vs C-index: 0.67, 95% CI: 0.66 to 0.68, p<0.001) as well as in low-risk patients (C-index: 0.64, 95% CI: 0.59 to 0.69 vs C-index: 0.57, 95% CI: 0.53 to 0.61, p=0.007). The GARFIELD-AF model was comparable to HAS-BLED in predicting the risk of major bleeding in patients on OAC therapy (C-index: 0.64, 95% CI: 0.63 to 0.66 vs C-index: 0.64, 95% CI: 0.63 to 0.65, p=0.60)., Conclusion: In a nationwide Danish cohort with non-valvular AF, the GARFIELD-AF model adequately predicted the risk of ischaemic stroke/SE and major bleeding. Our external validation confirms that the GARFIELD-AF model was superior to CHA 2 DS 2 VASc in predicting stroke/SE and comparable with HAS-BLED for predicting major bleeding., Competing Interests: Competing interests: KF has received research grants Bayer/Janssen and AstraZeneca and Consulting/Fees Bayer, Sanofi/Regeneron and Verseon. FV has received honoraria for consulting and presentations from Bayer HealthCare, Boehringer Ibgelheimy, BMSPfizer and Daiichi-Sankyo. GHG has ownership of stocks in Novo Nordisk Pharmaceuticals and reports research grants from Pfizer, Bristol Myers Squibb, Boehringer Ingelheim and Bayer. CTP declares grants for studies from Bayer. Other authors have no conflicts of interest to declare., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non-vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored., Methods: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ± antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016., Results: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP., Conclusion: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes., Objective: To assess the treatment strategies and 1-year clinical outcomes of antithrombotic and CHF therapies for patients with newly diagnosed AF with concomitant CHF stratified by etiology (ischemic cardiomyopathy [ICM] vs nonischemic cardiomyopathy [NICM])., Design, Setting, and Participants: The GARFIELD-AF registry is a prospective, noninterventional registry. A total of 52 014 patients with AF were enrolled between March 2010 and August 2016. A total of 11 738 patients 18 years and older with newly diagnosed AF (≤6 weeks' duration) and at least 1 investigator-determined stroke risk factor were included. Data were analyzed from December 2017 to September 2018., Exposures: One-year follow-up rates of death, stroke/systemic embolism, and major bleeding were assessed., Main Outcomes and Measures: Event rates per 100 person-years were estimated from the Poisson model and Cox hazard ratios (HRs) and 95% confidence intervals., Results: The median age of the population was 71.0 years, 22 987 of 52 013 were women (44.2%) and 31 958 of 52 014 were white (61.4%). Of 11 738 patients with CHF, 4717 (40.2%) had ICM and 7021 (59.8%) had NICM. Prescription of oral anticoagulant and antiplatelet drugs was not balanced between groups. Oral anticoagulants with or without antiplatelet drugs were used in 2753 patients with ICM (60.1%) and 5082 patients with NICM (73.7%). Antiplatelets were prescribed alone in 1576 patients with ICM (34.4%) and 1071 patients with NICM (15.5%). Compared with patients with NICM, use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (72.6% [3439] vs 60.3% [4236]) and of β blockers (63.3% [2988] vs 53.2% [3737]) was higher in patients with ICM. Rates of all-cause and cardiovascular death per 100 patient-years were significantly higher in the ICM group (all-cause death: ICM, 10.2; 95% CI, 9.2-11.1; NICM, 7.0; 95% CI, 6.4-7.6; cardiovascular death: ICM, 5.1; 95% CI, 4.5-5.9; NICM, 2.9; 95% CI, 2.5-3.4). Stroke/systemic embolism rates tended to be higher in ICM groups compared with NICM groups (ICM, 2.0; 95% CI, 1.6-2.5; NICM, 1.5; 95% CI, 1.3-1.9). Major bleeding rates were significantly higher in the ICM group (1.1; 95% CI, 0.8-1.4) compared with the NICM group (0.7; 95% CI, 0.5-0.9)., Conclusions and Relevance: Patients with ICM received oral anticoagulants with or without antiplatelet drugs less frequently and antiplatelets alone more frequently than patients with NICM, but they received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers more often than patients with NICM. All-cause and cardiovascular death rates were higher in patients with ICM than patients with NICM., Trial Registration: ClinicalTrials.gov Identifier: NCT01090362.

Aims: In Europe, the approved rivaroxaban dose for stroke prevention in patients with atrial fibrillation (AF) is 20 mg once daily (o.d.), with 15 mg o.d. recommended in patients with creatinine clearance (CrCl) 15-49 mL/min. Non-recommended doses are prescribed in real-world practice. This analysis of the XANTUS study assessed outcomes associated with non-recommended dosing and patient characteristics that may have impacted dose choice., Methods and Results: Baseline characteristics and 1 year outcomes were compared in 4464/6784 patients with known CrCl, receiving recommended or non-recommended rivaroxaban doses; 3608 (80.8%) patients received recommended doses (mean CHADS2 score 1.9) and 856 (19.2%) non-recommended doses (mean CHADS2 score 2.5). Incidence rate (events/100 patient-years) for the composite of treatment-emergent adjudicated major bleeding, stroke/systemic embolism, and death was 7.5 [95% confidence interval (CI) 5.7-9.8] and 4.8 (95% CI 4.1-5.7) with non-recommended and recommended doses, respectively [hazard ratio (HR) 1.55, 95% CI 1.2-2.1; P = 0.004]. Incidence rates for the components of the composite were 3.7 and 2.6, 1.4 and 0.9, and 3.5 and 1.9, respectively. Adjustment for baseline characteristics showed similar rates of the composite outcome (HR 1.06, 95% CI 0.77-1.45; P = 0.719). Multivariable analysis identified age, anaemia, congestive heart failure, diabetes mellitus, CrCl, lower body weight, AF type, and vascular disease as predictors of non-recommended dosing., Conclusion: Non-recommended rivaroxaban dosing was associated with less favourable outcomes, possibly due to baseline characteristics, in addition to renal function, that may also affect physicians' dosing decisions., Trial Registration Number: Clinicaltrials.gov: NCT01606995., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Aims: Based on Phase III data, non-vitamin K antagonist oral anticoagulants are recommended for stroke prevention in patients with atrial fibrillation. To determine whether trial outcomes translate into similar event rates in unselected patients, this analysis compared outcomes from the real-world XANTUS study with those from the Phase III ROCKET AF study., Methods and Results: Individual patient data from 4020 XANTUS patients were re-weighted to match the proportion of selected baseline characteristics in 7061 rivaroxaban-treated patients from ROCKET AF, using the matching-adjusted indirect comparison (MAIC) method. For the primary analysis, CHADS2 scores and gender were selected as relevant variables. Adjusted annualized incidence rates for XANTUS were calculated and compared with incidence rates from ROCKET AF-the ratio of these rates ('MAIC ratio') was used as a relative effect estimate. Rates of major bleeding [3.10%/year vs. 3.60%/year; MAIC ratio 0.86; 95% confidence interval (CI) 0.67-1.12] and stroke/non-central nervous system systemic embolism (1.54%/year vs. 1.70%/year; MAIC ratio 0.91; 95% CI 0.62-1.32) were similar between XANTUS and ROCKET AF. The rate of all-cause death was higher in XANTUS (3.22%/year vs. 1.87%/year; MAIC ratio 1.72; 95% CI 1.31-2.27), but the rates of vascular death were similar (1.83%/year vs. 1.53%/year; MAIC ratio 1.19; 95% CI 0.84-1.70). Sensitivity analyses weighted by different baseline characteristics supported these results., Conclusion: The low rates of major bleeding and stroke in XANTUS were consistent with results from ROCKET AF. All-cause death, but not vascular death, was higher in XANTUS, as expected in an unselected real-world population., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Background: Atrial fibrillation is associated with increased risks of death, stroke/systemic embolism, and bleeding (incurred by antithrombotic therapy), which may occur early after diagnosis., Methods: We assessed the risk of early events (death, stroke/systemic embolism, and major bleeding) over 12 months and their relation to the time after diagnosis of atrial fibrillation in 52 014 patients prospectively enrolled in the GARFIELD-AF registry (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) between March 2010 and August 2016., Results: Over 12 months, 2140 patients died (mortality rate, 4.3; 95% CI, 4.2-4.5 per 100 person-years), of whom 288 (13.5%) died in the first month (6.8; 95% CI, 6.1-7.6). Over 12 months, 657 patients had a stroke/systemic embolism (1.3; 95% CI, 1.2-1.4) and 411 had a major bleeding (0.8; 95% CI, 0.8-0.9). During the first month, the rates (per 100 person-years) of stroke/systemic embolism and major bleed were 2.3 (95% CI, 1.9-2.8) and 1.5 (95% CI, 1.2-1.9), respectively. The elevated 1-month mortality rate was mostly attributable to cardiovascular mortality (3.5; 95% CI, 3.0-4.1), in particular, heart failure, sudden death, and acute coronary syndromes (1.0 [95% CI, 0.8-1.4], 0.6 [95% CI, 0.4-0.8], and 0.5 [95% CI, 0.3-0.8], respectively). Age, heart failure, prior stroke, history of cirrhosis, vascular disease, moderate-to-severe kidney disease, diabetes mellitus, and living in North or Latin America were independent predictors of a higher risk of early death, whereas anticoagulation and living in Europe or Asia were independent predictors of a lower risk of early death. A predictive model developed for the 1-month risk of death had a C-statistic of 0.81 (95% CI, 0.78-0.83)., Conclusions: The increased hazard of early events, in particular, cardiovascular mortality, in newly diagnosed atrial fibrillation points to the importance of comprehensive care for such patients and should alert clinicians to detect warning signs of possible early mortality., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01090362.

Background: Four non-vitamin-K-antagonist oral anticoagulants (NOACs) have been approved for use in various cardiovascular indications. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban and rivaroxaban are now increasingly used in clinical practice. For some of these agents, available data from real-world studies support the efficacy and safety data in phase III clinical trials., Objectives: This review aims to summarize the current status of trials and observational studies of oral anticoagulant use over the spectrum of cardiovascular disorders (excluding venous thrombosis), provide a reference source beyond stroke prevention for atrial fibrillation (AF) and examine the potential for novel applications in the cardiovascular field., Methods: We searched the recent literature for data on completed and upcoming trials of oral anticoagulants with a particular focus on rivaroxaban., Results: Recent data in specific patient subgroups, such as patients with AF undergoing catheter ablation or cardioversion, have led to an extended approval for rivaroxaban, whereas the other NOACs have ongoing or recently completed trials in this setting. However, there are unmet medical needs for several arterial thromboembolic-related conditions, including patients with: AF and acute coronary syndrome, AF and coronary artery disease undergoing elective percutaneous coronary intervention, coronary artery disease and peripheral artery disease, implanted cardiac devices, and embolic stroke of unknown source., Conclusion: NOACs may provide alternative treatment options in areas of unmet need, and numerous studies are underway to assess their benefit-risk profiles in these settings.