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Clinical risk scores that predict outcomes in patients with atrial fibrillation (AF) have modest predictive value. Machine learning (ML) may achieve greater results when predicting adverse outcomes in patients with recently diagnosed AF. Several ML models were tested and compared with current clinical risk scores on a cohort of 26,183 patients (mean age 70.13 (standard deviation 10.13); 44.8% female) with non-valvular AF. Inputted into the ML models were 23 demographic variables alongside comorbidities and current treatments. For one-year stroke prediction, ML achieved an area under the curve (AUC) of 0.653 (95% confidence interval 0.576-0.730), compared to the CHADS 2 and CHA 2 DS 2 -VASc scores performance of 0.587 (95% CI 0.559-0.615) and 0.535 (95% CI 0.521-0.550), respectively. Using ML for one-year major bleed prediction increased the AUC from 0.537 (95% CI 0.518-0.557) generated by the HAS-BLED score to 0.677 (95% CI 0.619-0.724). ML was able to predict one-year and three-year all-cause mortality with an AUC of 0.734 (95% CI 0.696-0.771) and 0.742 (95% CI 0.718-0.766). In this study a significant improvement in performance was observed when transitioning from clinical risk scores to machine learning-based approaches across all applications tested. Obtaining precise prediction tools is desirable for increased interventions to reduce event rates.Trial Registry https://www.clinicaltrials.gov ; Unique identifier: NCT01468701, NCT01671007, NCT01937377., (© 2024. The Author(s).)

Objectives: Post-cardiac and aortic surgery stroke is often underreported. We detail our single-centre experience the following introduction of comprehensive consultant-led daily stroke service, to demonstrate the efficacy of a stroke team in recovery from stroke following cardiac and aortic surgeries., Methods: This retrospective, single-centre observational cohort study analysed consecutive patients undergoing cardiac and aortic surgery at our institution from August 2014 to December 2020. Main outcomes included stroke rate, predictors of stroke, and neurological deficit resolution or persistence at discharge and clinic follow-up., Results: A total of 12,135 procedures were carried out in the reference period. Among these, 436 (3.6%) suffered a stroke. Overall survival to discharge and follow-up were 86.0% and 84.0% respectively. Independent risk factors for post-operative stroke included advanced age (OR 1.033, 95% CI [1.023, 1.044], p < .001), female sex (OR 1.491, 95% [1.212, 1.827], p < .001), history of previous cardiac surgeries (OR 1.670, 95% CI [1.239, 2.218], p < .001), simultaneous coronary artery bypass graft + valve procedures (OR 1.825, 95% CI [1.382, 2.382], p < .001) and CPB time longer than 240 min (OR 3.384, 95% CI [2.413, 4.705], p < .001). Stroke patients managed by the multidisciplinary team demonstrated significantly higher rates of survival at discharge (87.3% vs. 61.9%, p = .001)., Conclusions: Perioperative stroke can be debilitating immediately long term. The involvement of specialist stroke teams plays a key role in reducing the long-term burden and mortality of this condition., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Stroke prevention and symptom control are two integral pillars in atrial fibrillation (AF) management. Percutaneous left atrial appendage occlusion (LAAO) is effective at reducing stroke risk in high-risk patients with AF who cannot tolerate oral anticoagulant therapy, whilst catheter ablation is effective at reducing AF burden and improving quality-of-life in patients who remain symptomatic despite medical therapy. If both procedures are indicated in an individual patient, they have traditionally been performed on separate occasions, due to long cumulative procedural times, itself associated with thromboembolic risk. Recently, with the advancement of procedural techniques, the concept of concurrent LAAO and AF catheter ablation has gained traction. This review summarises the evidence for and against concurrent LAAO and AF catheter ablation, discussing procedural considerations, including procedural sequencing and post-procedural antithrombotic therapy, safety and efficacy outcomes, and future directions in the field., (Copyright © 2023. Published by Elsevier Inc.)

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.

Female sex has been suggested as a risk modifier for stroke in patients with atrial fibrillation (AF) with comorbid prevalent stroke risk factors. Management has evolved over time towards a holistic approach that may have diminished any sex difference in AF-related stroke. In a nationwide cohort of AF patients free from oral anticoagulant treatment, we examine the time trends in stroke risk overall and in relation to risk differences between male and female patients. Here we show that among 158,982 patients with AF (median age 78 years (IQR: 71 to 85); 52% female) the 1-year thromboembolic risk was highest between 1997-2000 with a risk of 5.6% and lowest between 2013-2016 with a risk of 3.8%, declining over the last two decades. The excess stroke risk for female vs male patients has also been declining, with risk-score adjusted relative risk estimates suggesting limited sex-difference in recent years., (© 2024. The Author(s).)

Stroke prevention following successful catheter ablation of atrial fibrillation remains a controversial topic. Oral anticoagulation is associated with a significant reduction in stroke risk in the general atrial fibrillation population but may be associated with an increased risk of major bleeding, and the benefit: risk ratio must be considered. Improvement in successful catheter ablation and widespread use of cardiac monitoring devices may allow for novel anticoagulation strategies in a subset of patients with atrial fibrillation, which may optimize stroke prevention while minimizing bleeding risk. In this review, we discuss stroke risk in atrial fibrillation and the effects of successful catheter ablation on thromboembolic risk. We also explore novel strategies for stroke prevention following successful catheter ablation., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice., Materials and Methods: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB., Results and Conclusions: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs., (© 2024. The Author(s).)

Aims: Women with atrial fibrillation (AF) are under-represented in randomised controlled trials (RCTs) of direct oral anticoagulants (DOACs). This systematic review and meta-analysis of RCTs and observational studies examined sex-specific outcomes of DOACs in AF., Methods: PubMed, Embase, Web of Science and Cochrane Library were searched from January 2008 to November 2022. Sex-specific comparative outcomes of stroke/systemic embolism (SE), major bleeding, intracranial haemorrhage (ICH) and gastrointestinal bleeding (GIB) between oral anticoagulants were pooled using random effects models. P values for interaction were calculated to examine differences in results between sexes. RCTs and observational studies were meta-analysed separately., Results: 5 RCTs and 33 observational studies were included, totalling 1 085 931 women and 1 387 123 men. Meta-analyses showed that for both sexes, DOAC versus warfarin was generally associated with lower risk of stroke/SE, major bleeding and ICH; in DOAC-DOAC comparisons, rivaroxaban versus dabigatran had higher GIB risk. The only sex-specific difference observed was that when compared with warfarin, women had higher GIB risk with rivaroxaban (women: pooled risk ratio (pRR)=1.34, 95% CI=1.18 to 1.51; men: pRR=0.97, 95% CI=0.85 to 1.10; p value for interaction (p for interaction)<0.001) and possibly dabigatran (women: pRR=1.25, 95% CI=0.92 to 1.70; men: pRR=0.83, 95% CI=0.72 to 0.97; p-for-interaction=0.02). The sex difference in GIB remained for rivaroxaban when a Bonferroni-corrected significance level was used (α=0.003). No sex-specific GIB data for apixaban and edoxaban was available for the meta-analysis., Conclusions: For both sexes, DOACs generally demonstrated favourable effectiveness and safety over warfarin. However, observational data suggested that women may have higher GIB risk with rivaroxaban and possibly dabigatran than warfarin. Further studies are warranted to verify our findings and elucidate sex-specific GIB risk with apixaban and edoxaban, of which the data is currently lacking., Prospero Registration Number: CRD42022325027., Competing Interests: Competing interests: ZW’s current post is partly supported by the AIR@InnoHK administered by Innovation and Technology Commission. KKCM was supported by the CW Maplethorpe Fellowship and received research funding from the National Institute of Health Research, UK, European Commission Horizon 2020 framework and Hong Kong Research Grants Council and personal fee from IQVIA, outside the scope of the submitted work. GYHL is consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo, no fees was received personally. ICKW has received research funding from the National Institute of Health Research, UK, European Commission Horizon 2020 framework, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, Amgen, Janssen, Novartis and GSK for medication safety research, outside the scope of the submitted work. He also received funding from Bristol-Myers Squibb, Pfizer and Bayer on DOACs research but it is not associated with the current study. His current post is partly funded by the AIR@InnoHK administered by Innovation and Technology Commission. WL reported research funding from the AIR@InnoHK administered by Innovation and Technology Commission, outside the scope of the submitted work. There are no other relationships or activities to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although early rhythm control (ERC) in patients with atrial fibrillation (AF) reduces the risk of stroke, there is no evidence thus far on whether ERC reduces the risk of developing dementia in patients with AF and prior stroke., Objectives: This study sought to evaluate whether ERC reduces the risk of developing dementia in patients with new-onset AF and prior stroke., Methods: Using the Korean nationwide claims database, we identified patients with new-onset AF and prior stroke between 2010 and 2016. Patients who received rhythm control therapy within 1 year after AF onset were defined as the ERC group, otherwise patients were categorized as the usual care group. A propensity score weighting method was used to balance the 2 groups. Incident dementia defined by relevant diagnostic codes was evaluated., Results: A total of 41,370 patients were included (mean age 70 ± 11 years; mean CHA 2 DS 2 -VASc score 5.3 ± 1.6): 10,213 in the ERC group and 31,157 in the usual care group. Compared with usual care, ERC was associated with lower risks of all dementia, Alzheimer's dementia, and vascular dementia (weighted HR: 0.825 [95% CI: 0.776-0.876], 0.831 [95% CI: 0.774-0.893], and 0.800 [95% CI: 0.702-0.913], respectively, all P < 0.001). The benefit of ERC was slightly accentuated in the younger age group (<65 years). The beneficial effect of ERC in reducing the risk of dementia was consistent regardless of the characteristics of prior stroke., Conclusions: ERC might be beneficial in the prevention of dementia in patients with AF and prior stroke. To prevent the progression of cognitive dysfunction, ERC should be considered in this population., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202013B14), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (grant 2020R1F1A106740). Dr Choi has received research grants or speaking fees from Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daiichi-Sankyo, Dreamtech Co., Ltd., Medtronic, Samjinpharm, Sanofi-Aventis, Seers Technology, Skylabs, and Yuhan. Dr Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo, but no fees are received personally; no other relationships or activities that could appear to have influenced the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Stroke prevention is central to the management of atrial fibrillation (AF), but there remains a residual risk of adverse outcomes in anticoagulated AF patients. Hence, current guidelines have proposed a more holistic or integrated approach to AF management, based on the Atrial fibrillation Better Care (ABC) pathway, as follows: (A) avoid stroke with anticoagulation; (B) better symptom control with patient-centred symptom directed decisions on rate or rhythm control; and (C) cardiovascular and comorbidity management, including lifestyle factors. There has been no formal healthcare cost analysis from the UK National Health Service (NHS) perspective of ABC pathway implementation to optimize the management of AF. Our aim was to estimate the number of patients with AF in the UK each year up to 2040, their morbidity and mortality, and the associated healthcare costs, and secondly, to estimate improvements in morbidity and mortality of implementing an ABC pathway, and the impact on costs., Results: In 2020, there were an estimated 1 463 538 AF patients, resulting in £286 million of stroke care and £191 million of care related to bleeds annually. By 2030, it is expected that there will be 2 115 332 AF patients, resulting in £666 million of stroke healthcare and £444 million of healthcare related to bleeds. By 2040, this is expected to rise to 2 856 489 AF patients, with £1096 million of stroke healthcare and £731 million of healthcare related to bleeds for that year. If in 2040 patients are managed on an ABC pathway, this could prevent between 3724 and 18 622 strokes and between 5378 and 26 890 bleeds, and save between 16 131 and 80 653 lives depending on the proportion of patients managed on the pathway. This would equate to cost reductions of between £143.9 million and £719.6 million for the year., Conclusion: We estimate that there will be a substantial healthcare burden in the UK NHS associated with AF, from strokes, bleeds, and mortality over the next decades. If patients are managed with a holistic or integrated care approach based on the ABC pathway, this could prevent strokes and bleeds that equate to substantial NHS healthcare cost reductions, and save lives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function., Methods: Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding., Results: Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49 mL/min/1.73 m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73 m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49 mL/min/1.73 m2., Conclusions: Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30 mL/min/1.73 m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49 mL/min/1.73 m2., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We investigated the association between atrial fibrillation (AF) and dementia, and its subtypes (vascular-VaD, Alzheimer, mixed and rare dementia), and identified predictors for dementia in AF patients., Methods: The analysis was based on 183,610 patients with new-onset AF and 367,220 non-AF controls in the United Kingdom between 1998 and 2016, identified in three prospectively collected, linked electronic health records sources. Time-to-event (dementia or subtypes) analyses were performed using Cox proportional hazards and weighted Cox. Sub-analyses performed: including & censoring stroke and age (median used as cut-off)., Results: Over a median follow-up of 2.67 years (IQR .65-6.02) for AF patients and 5.84 years for non-AF patients (IQR 2.26-11.80), incidence of dementia in the AF cohort was 2.65 per 100 person-years, compared to 2.02 in the non-AF cohort. After adjustment, a significant association was observed between AF and all-cause dementia (HR = 1.38, 95% CI: 1.31-1.45), driven by a strong association with VaD (HR = 1.55, 95% CI: 1.41-1.70). AF was also associated with mixed dementia (HR = 1.26, 95% CI: 1.01-1.56), but we could not confirm an association with Alzheimer (HR = 1.05, 95% CI: .94-1.16) and rare dementia forms (HR = 1.19, 95% CI: .90-1.56). Ischemic stroke (HR = 1.40, 95% CI: 1.26-1.56), subarachnoid haemorrhage (HR = 2.08, 95% CI: 1.47-2.96), intracerebral haemorrhage (HR = 1.95, 95% CI: 1.54-2.48) and diabetes (HR = 1.32, 95% CI: 1.24-1.41) were identified as the strongest predictors of dementia in AF patients., Conclusions: AF patients have an increased risk of dementia, independent of stroke, with highest risk of VaD. Management and prevention of the identified risk factors could be crucial to reduce the increasing burden of dementia., (© 2024 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Anticoagulation therapy (AT) is fundamental in atrial fibrillation (AF) treatment but poses challenges in implementation, especially in AF populations with elevated thromboembolic and bleeding risks. Current guidelines emphasize the need to estimate and balance thrombosis and bleeding risks for all potential candidates of antithrombotic therapy. However, administering oral AT raises concerns in specific populations, such as those with chronic kidney disease (CKD), coagulation disorders, and cancer due to lack of robust data. These groups, excluded from large direct oral anticoagulants trials, rely on observational studies, prompting physicians to adopt individualized management strategies based on case-specific evaluations. The scarcity of evidence and specific guidelines underline the need for a tailored approach, emphasizing regular reassessment of risk factors and anticoagulation drug doses. This narrative review aims to summarize evidence and recommendations for challenging AF clinical scenarios, particularly in the long-term management of AT for patients with CKD, coagulation disorders, and cancer., Competing Interests: Declaration of competing interest GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. He is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk., Methods and Analysis: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis., Ethics and Dissemination: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee., Trial Registration Number: ISRCTN72104369., Competing Interests: Competing interests: JM has performed consultancy work for BMS/Pfizer and Omron. FDRH reports occasional consultancy for BMS/Pfizer, Bayer and BI over the past 5 years. NA is a member of the UK National Screening Committee. MC and MS are employed by AstraZeneca, but at the time of involvement with the trial were employed by universities (King's College London and University of Leicester, respectively), for which they still hold honorary contracts. RJM’s employer, the University of Oxford, receives consultancy and licensing payments from Omron and Sensyne for BP telemonitoring interventions. GYHL is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo and Anthos. No fees are received personally. SJG has received honoraria from AstraZeneca for lectures at postgraduate educational meetings for primary care teams about type 2 diabetes. BF has received speaker fees, honoraria and non-financial support from BMS and Pfizer Alliance; grants to the institution for investigator-initiated studies from BMS and Pfizer Alliance; and loan devices for investigator-initiated studies from Alivecor, all were unrelated to the present trial but related to screening for AF., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes., Methods: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed., Results: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively)., Conclusions: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis., (© 2024. The Author(s).)

Objective: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF., Methods: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated., Results: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02)., Conclusion: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management., Competing Interests: Competing interests: E-KC: Research grants or speaking fees from Abbott, Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daewoong Pharmaceutical Co, Daiichi-Sankyo, DeepQure, Dreamtech Co, Ltd, Jeil Pharmaceutical Co Ltd, Medtronic, Samjinpharm, Seers Technology, and Skylabs. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos and Daiichi-Sankyo. No fees are received personally. GYHL is coprincipal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 899871., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Atrial fibrillation (AF) is a significant risk factor for stroke. Based on the higher stroke associated with AF in the South Asian population, we constructed a one-year stroke prediction model using machine learning (ML) methods in KERALA-AF South Asian cohort. External validation was performed in the prospective APHRS-AF registry. We studied 2101 patients and 83 were to patients with stroke in KERALA-AF registry. The random forest showed the best predictive performance in the internal validation with receiver operator characteristic curve (AUC) and G-mean of 0.821 and 0.427, respectively. In the external validation, the light gradient boosting machine showed the best predictive performance with AUC and G-mean of 0.670 and 0.083, respectively. We report the first demonstration of ML's applicability in an Indian prospective cohort, although the more modest prediction on external validation in a separate multinational Asian registry suggests the need for ethnic-specific ML models., Competing Interests: Declaration of competing interest G.Y.H.L. reports: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. G.Y.H.L. is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871. Other authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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: Atrial fibrillation (AF) is the most common sustained arrhythmia and results in a high risk of stroke. The number of immigrants is increasing globally, but little is known about potential differences in AF care across migrant populations., Aim: To investigate if initiation of oral anticoagulation therapy (OAC) differs for patients with incident AF in relation to country of origin., Methods: A nationwide register-based study covering 1999-2017. AF was defined as a first-time diagnosis of AF and a high risk of stroke. Stroke risk was defined according to guidelines from the European Society of Cardiology (ESC). Poisson regression adjusted for sex, age, socioeconomic position and comorbidity was made to compute incidence rate ratios (IRR) for initiation of OAC., Results: The AF population included 254 586 individuals of Danish origin, 6673 of Western origin and 3757 of non-Western origin. Overall, OAC was initiated within -30/+90 days relative to the AF diagnosis in 50.3% of individuals of Danish origin initiated OAC, 49.6% of Western origin and 44.5% of non-Western origin. Immigrants from non-Western countries had significantly lower adjusted IRR of initiating OAC according to all ESC guidelines compared with patients of Danish origin. The adjusted IRRs ranged from 0.73 (95% CI: 0.66 to 0.80) following the launch of the 2010 ESC guideline to 0.89 (95% CI: 0.82 to 0.97) following the launch of the 2001 ESC guideline., Conclusion: Patients with AF with a high risk of stroke of non-Western origin have persistently experienced a lower chance of initiating OAC compared with patients of Danish origin during the last decades., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest: B.J.R.B. has received research funding from Bristol Myers Squibb (BMS)/Pfizer. S.L.H. has received funding from BMS. D.A.L. has received investigator-initiated educational grants from Bristol Myers Squibb (BMS) and Pfizer; been a speaker for Boehringer Ingelheim, Bayer, and BMS/Pfizer and consulted for Boehringer Ingelheim, Bayer, and BMS/Pfizer; all outside the submitted work. G.Y.H.L.: consultant and speaker for BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally.

Background: In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies., Methods: This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone., Results: The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052-1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454-0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529-0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478-0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231-1.880), ICH (aHR 2.045, 95% CI 1.329-3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB., Conclusions: For post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy., (© 2024. The Author(s).)

Background and Aims: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF., Methods: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort., Results: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death)., Conclusions: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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 and Purpose: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE)., Methods: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest., Results: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE., Conclusions: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background:  Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes., Methods:  Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group)., Results:  The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching., Conclusion:  In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a hospital diagnosis of non-valvular atrial fibrillation (NVAF)., Methods and Results: Of 170404 OAT-naïve patients (mean age 78.7 years; 49.4 % women), only 61.1 % were prescribed direct oral anticoagulants, DOACs, or vitamin-K antagonists, VKAs; 14.2 % were given aspirin (ASA), and 24.8 % no anti-thrombotic drugs (No Tx). We compared ischemic stroke (IS), IS and systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding (MB), major gastro-intestinal bleeding, all-cause deaths and the composite outcome, across four propensity-score matched treatment cohorts with >15400 patients each. Over 2.9±1.5 years, the incidence of IS and IS/SE was slightly less with VKAs than with DOACs (1.62 and 1.84 vs 1.81 and 1.99 events.100 person-years; HR=0.85, 95%CI=0.76-0.95 and HR=0.87, 95%CI=0.78-0.97). This difference disappeared in a sensitivity analysis which excluded those patients treated with low-dose of apixaban, edoxaban, or rivaroxaban (41.7% of DOACs cohort). Compared with DOACs, VKAs were associated with greater incidence of ICH (1.09 vs 0.81; HR=1.38, 95%CI=1.17-1.62), MB (3.78 vs 3.31; HR=1.14, 95%CI=1.02-1.28), all-cause mortality (9.66 vs 10.10; HR=1.07, 95%CI=1.02-1.11), and composite outcome (13.72 vs 13.32; HR=1.04, 95%CI=1.01-1.08). IS, IS/SE, and mortality were more frequent with ASA or No Tx than with VKAs or DOACs (p<0.001 for all comparisons)., Conclusions: Beyond confirming the association with a better net clinical benefit of DOACs over VKAs, our findings substantiate the large proportion of NVAF patients still inappropriately anticoagulated, thereby reinforcing the need for educational programs., Competing Interests: Declaration of Competing Interest SF: speaker for BMS/Pfizer, Bruno Farmaceutici, Daiichi-Sankyo, Menarini Group; research grants from Menarini Group. GYHL: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. GYHL is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 899871. NM: Consultant and speaker for BMS/Pfizer, Bayer, Daiichi-Sankyo. The other Authors declare they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Aim: Atrial fibrillation (AF) is associated with increased risk of dementia. Whether direct oral anticoagulation (DOAC) reduce this risk compared to vitamin-K antagonist (VKA) is unclear. The aim of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs., Methods: Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score-matched with those treated with a VKA. The analysis included patients who completed 5 and 10 years of follow-up and were assessed for all-cause dementia and vascular dementia. Cox proportional hazard models were used to hazard ratios (HR), respectively with 95% confidence intervals (CIs)., Results: Among patients who completed 5 years of follow-up, after propensity score matching the final cohort consisted of 215,404 well-matched AF patients. All-cause dementia was diagnosed in 4,153 (3.9%) patients among those treated with DOACs and 4,150 (3.9%) among the VKA-treated patients (HR: 1.01, 95%CI: 0.96-1.05). Among patients 65-74 years old who were followed, DOAC treatment was associated with lower risk of dementia compared to VKAs (HR: 0.72; 95%CI: 0.59-0.86). Among patients who completed 10 years of follow-up, after propensity score matching the final cohort consisted of 19,208 well-matched AF patients. All-cause dementia was diagnosed in 314 (3.3%) patients among those treated with DOACs and 451 (4.7%) among the VKA-treated patients. DOAC treatment was associated with significantly lower risk of all-cause dementia during a follow-up period of 10 years compared to VKA treatment (HR: 0.72, 95%CI: 0.62-0.83), which remained consistent in patiens ≥65 years old., Conclusion: This propensity-score matched analysis showed that among AF patients, treatment with a DOACs for a period of 10 years was associated with lower risk of all-cause dementia and vascular dementia compared to VKA treatment, an effect which was not apparent in those treated for shorter duration. This finding requires confirmation in ongoing randomised controlled trials., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Phenotypic classification is a method of grouping patients with similar phenotypes., Aim: We aimed to use phenotype classification based on a clustering process for risk stratification of patients with non-valvular atrial fibrillation (AF) and second, to assess the benefit of the Atrial Fibrillation Better Care (ABC) pathway., Methods: Patients with AF were prospectively enrolled from 27 hospitals in Thailand from 2014 to 2017, and followed up every 6 months for 3 years. Cluster analysis was performed from 46 variables using the hierarchical clustering using the Ward minimum variance method. Outcomes were a composite of all-cause death, ischemic stroke/systemic embolism, acute myocardial infarction and heart failure., Results: A total of 3405 patients were enrolled (mean age 67.8 ± 11.3 years, 58.2% male). During the mean follow-up of 31.8 ± 8.7 months. Three clusters were identified: Cluster 1 had the highest risk followed by Cluster 3 and Cluster 2 with a hazard ratio (HR) and 95% confidence interval (CI) of composite outcomes of 2.78 (2.25, 3.43), P < 0.001 for Cluster 1 and 1.99 (1.63, 2.42), P < 0.001 for Cluster 3 compared with Cluster 2. Management according to the ABC pathway was associated with reductions in adverse clinical outcomes especially those who belonged to Clusters 1 and 3 with HR and 95%CI of the composite outcome of 0.54 (0.40, 073), P < 0.001 for Cluster 1 and 0.49 (0.38, 0.63), P < 0.001 for Cluster 3., Conclusion: Phenotypic classification helps in risk stratification and prognostication. Compliance with the ABC pathway was associated with improved clinical outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Frail people with atrial fibrillation are often undertreated with oral anticoagulants (OACs), and evidence for the net clinical benefit (NCB) of OAC is sparse. We, therefore, examined the risk of thromboembolic events, major bleeding, and NCB of anticoagulation treatment., Methods: This was a nationwide cohort study including frail patients aged with incident atrial fibrillation between 2013 and 2018. Patients were categorized according to OAC treatment exposure. One-year risks of thromboembolic events and major bleeding were ascertained where death was treated as a competing risk. The NCB of anticoagulation was assessed by a bivariate trade-off between thromboembolism and bleeding., Results: We identified 36 223 frail patients with atrial fibrillation (median age, 79 years; 50.5% female), of whom 61.8% started OAC therapy, while 38.2% were untreated despite indication for stroke prevention. At 1 year, the risk of thromboembolic events was 2.1% (95% CI, 1.8%-2.3%) among patients not receiving OAC versus 1.5% (95% CI, 1.4%-1.7%) in patients with OAC. The bleeding risk was 3.2% (95% CI, 2.9%-3.5%) among patients without OAC versus 3.5% (95% CI, 3.2%-3.8%) among anticoagulated patients. The NCB was 0.70% (95% CI, 0.32%-1.08%), suggesting a benefit of OAC treatment; however, the NCB declined with age and increasing frailty and was lowest among patients >75 years of age or with high frailty level., Conclusions: Frail patients with atrial fibrillation are often untreated with OAC in routine clinical care despite an indication for stroke prevention. The NCB balancing thromboembolic events and major bleeding was in favor of anticoagulation but decreased with advancing age and increasing frailty., Competing Interests: Disclosures Dr Søgaard has received speaker fees from Bayer. Dr Højen reports compensation from Bayer for consultant services and other services; compensation from LEO Pharma AS for other services; compensation from Bristol Myers Squibb (BMS) for consultant services; compensation from Pfizer for other services; and grants from Novo Nordisk Fonden. Dr Lip is a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, and Daiichi Sankyo. No fees are received personally. Dr Larsen is an investigator for Janssen Scientific Affairs, LLC, Bayer AG, and Boehringer Ingelheim and reports speaker honorarium from Bayer, BMS, Pfizer, and Merck, Sharp & Dome. Dr Nielsen reports consultant fees from Boehringer Ingelheim, grants and consultant fees from Daiichi Sankyo, grants from BMS/Pfizer, and grants and consultant fees from Bayer outside the submitted work. The other authors report no conflicts.

Aims: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i)., Materials and Methods: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality., Results: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i., Conclusions: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i., (© 2024 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Aims: Data on the optimal use of antithrombotic drugs and associated clinical outcomes in patients with atrial fibrillation (AF) and acute ischaemic stroke (IS) are limited. We investigated the prescription patterns of antithrombotics in community practice and long-term clinical prognosis according to early post-stroke antithrombotic therapy in patients with AF and acute IS., Methods and Results: Patients with AF who were admitted for acute IS at a single tertiary hospital in 2010-2020 were retrospectively reviewed. Clinical profiles including the aetiology of stroke and prescription patterns of antithrombotics were identified. The net clinical outcome (NCO)-the composite of recurrent stroke, any bleeding, hospitalization or emergency department visits for cardiovascular (CV) events, and death-was compared according to the antithrombotic therapy at the first outpatient clinic visit [oral anticoagulation (OAC) alone vs. antiplatelet (APT) alone vs. OAC/APT(s)] following discharge. A total of 918 patients with AF and acute IS (mean age, 72.6 years; male, 59.3%; mean CHA₂DS₂-VASc score 3.3) were analysed. One-third (33.9%, n = 310) of patients were simultaneously diagnosed with AF and IS. The most common aetiology of IS was cardioembolism (71.2%), followed by undetermined aetiology (19.8%) and large artery atherosclerosis (6.0%). OAC, APT(s), and concomitant OAC and APT(s) were prescribed in 33.4%, 11.1%, and 53.4% of patients during admission that changed to 67.0%, 9.1%, and 21.7% at the first outpatient clinic, and were mostly continued up to one year after IS. Non-prescription of OAC was observed in 11.3% of post-stroke patients with AF. During a median follow-up of 2.1 years, the overall incidence rate of NCO per 100 patient-year (PY) was 20.14. APT(s) monotherapy presented the highest cumulative risk of NCO (adjusted hazard ratio 1.47, 95% confidence interval 1.08-2.00, P = 0.015; with reference to OAC monotherapy) mainly driven by the highest rates of recurrent stroke and any bleeding. OAC/APT(s) combination therapy was associated with a 1.62-fold significantly higher risk of recurrent stroke (P = 0.040) and marginally higher risk of any bleeding than OAC monotherapy., Conclusion: Approximately one-third of acute IS in AF have a distinctive mechanism from cardioembolism. Although APT was frequently prescribed in post-stroke patients with AF, no additive clinical benefit was observed. Adherence to OAC treatment is essential to prevent further CV adverse events in patients with AF and IS., Competing Interests: Conflict of interest: H.-J.A., J.M.C., K.-Y.L., S.K., S.O.: none. S.-R.L.: speaking fees from Bayer, BMS/Pfizer, Biosense Webster, Daiichi-Sankyo, Sanofi-Aventis, Daewoong Pharmaceutical Co., Samjinpharm, Seers Technology, Biotronik, Boston Scientific, and Medtronic. Consultant for Biosense Webster. No fees are received personally and no fees are related to this work. E.-K.C.: research grants or speaking fees from Abbott, Bayer, BMS/Pfizer, Biosense Webster, Chong Kun Dang, Daewoong Pharmaceutical Co., Daiichi-Sankyo, DeepQure, Dreamtech Co., Ltd., Jeil Pharmaceutical Co. Ltd, Medtronic, Samjinpharm, Seers Technology, and Skylabs. G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos, and Daiichi-Sankyo. No fees are received personally. G.Y.H.L. is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 899871., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China., Methods: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed., Results: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  <0.001). At discharge, the prescription rate of OAC was 45.2% (16,757/37,087) in eligible patients with high stroke risk and 60.7% (2778/4578) in eligible patients with low stroke risk. OAC utilization in patients with high stroke risk on admission or at discharge both increased largely over time (all P  <0.001). Multivariate analysis showed that OAC utilization at discharge was positively associated with in-hospital rhythm control strategies, including catheter ablation (adjusted odds ratio [OR] 11.63, 95% confidence interval [CI] 10.04-13.47; P <0.001), electronic cardioversion (adjusted OR 2.41, 95% CI 1.65-3.51; P <0.001), and anti-arrhythmic drug use (adjusted OR 1.45, 95% CI 1.38-1.53; P <0.001)., Conclusions: In hospitals participated in the CCC-AF project, >70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background and Objectives: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis., Methods: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression., Results: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome., Discussion: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Background: Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) is a prospective registry of outcomes from patients with newly diagnosed AF at risk of stroke. In the propensity score (PS)-matched global population of phase 3 GLORIA-AF, at 3 years, dabigatran-treated patients experienced reduced risk for major bleeding, and similar risk for stroke and myocardial infarction, compared with vitamin K antagonist (VKA)-treated patients., Study Question: Do patients in Eastern Europe benefit from treatment with dabigatran versus VKA?, Study Design: Descriptive analysis, without PS matching. To contextualize the Eastern Europe results of GLORIA-AF phase 3, we also descriptively analyzed the global population without PS matching. Consecutive patients with newly diagnosed AF and CHA2DS2-VASc-score ≥1 were enrolled until December 2016 in 38 countries (9 in Eastern Europe)., Measures and Outcomes: Three-year outcomes with dabigatran and VKA., Results: In Eastern Europe, 1341 patients were eligible (6% of patients globally), and incidence rates (per 100 patient-years) for the following outcomes were numerically lower with dabigatran (N = 498) versus VKA (N = 466): major bleeding (0.26 vs. 0.90), all-cause death (2.04 vs. 3.50), and a composite of stroke, systemic embolism, myocardial infarction, life-threatening bleeding, and vascular death (1.37 vs. 1.92); stroke was comparable (0.51 vs. 0.50). All incidence rates were numerically lower in Eastern Europe versus the global population for both treatments. Chronic concomitant use of high bleeding risk medications (eg, nonsteroidal anti-inflammatories) was lower in Eastern Europe (dabigatran 3.8%, VKA 9.3%) than globally (dabigatran 14.8%, VKA 20.6%) and persistence with dabigatran was higher in Eastern Europe (76%) than globally (64%)., Conclusions: Dabigatran was associated with numerically reduced major bleeding, all-cause death, and cardiovascular (CV) composite, with comparable risk of stroke versus VKA, in Eastern Europe. Limitations of this descriptive analysis include few CV events (n = 11 for stroke, in the dabigatran and VKA groups combined) and a lack of statistical analysis and PS matching, which precludes definitive conclusions; however, the CV outcomes in Eastern Europe were consistent with the beneficial impact of dabigatran versus VKA in the statistically analyzed global population with PS matching., Competing Interests: J. Bergler-Klein reports no conflicts of interest. N. Gotcheva reports no conflicts of interest. O. Kalējs reports grants and personal fees from Bayer and Boehringer Ingelheim. Z. Kalarus has lectured for Boehringer Ingelheim. D. Kovačić reports no conflicts of interest. V. Peršić reports no conflicts of interest. E. Shlyakhto reports no conflicts of interest. T. Uuetoa reports grants and personal fees from Bayer and Boehringer Ingelheim. M. V. Huisman reports grants from ZonMW Dutch Healthcare Fund, and grants and consultation honoraria from Boehringer Ingelheim, Pfizer/Bristol-Myers Squibb, Bayer Health Care, Aspen, and Daiichi-Sankyo. G. Y. H. Lip reports consultancy and speaking for BMS/Pfizer, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. D. Vinereanu reports grants and personal fees from Bayer, Boehringer Ingelheim, and Pfizer., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks., Design: Population-based retrospective cohort study., Participants: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching., Exposure: Warfarin use within 14 days of IE diagnosis., Main Outcomes and Measures: Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up., Results: The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70-1.53]), intracranial hemorrhage (HR:1.25 [0.77-2.04]), and gastrointestinal bleeding (HR:1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34-8.31]), but not at 90-day (sub-HR:1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression., Conclusions and Relevance: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis., Key Points: Question: Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe?, Findings: In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning: In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background:  Atrial fibrillation (AF) Better Care (ABC) pathway adherence is associated with improved outcomes. Clinical trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) are as least as effective as warfarin for stroke prevention in AF patients. The Win Ratio method, analyzing hierarchical composite outcomes considering event timing and severity, has limited data on its use in Asians., Objectives:  We aim to apply Win Ratio in a registry to access the comparative effectiveness of NOACs versus warfarin and ABC adherence versus nonadherence in Asian patients with AF., Methods:  Our study included nonvalvular AF patients from the nationwide prospective COOL-AF registry in Thailand. The NOAC-treated group was compared with the warfarin-treated group using the Win Ratio, with the following order: all-cause death, intracranial hemorrhage (ICH), ischemic stroke/transient ischemic attack/systemic embolism, non-ICH major bleeding, and myocardial infarction or heart failure. ABC pathway adherence versus nonadherence was also compared. A Win Ratio greater than 1.00 indicating a better outcome., Results:  The analysis included 2,568 patients, with 228 in the NOAC group and 2,340 in the warfarin group. The NOAC group had more wins than the warfarin group, with an unmatched Win Ratio of 1.64 (95% confidence interval [CI]: 1.22-2.20; p  < 0.001). When compared with nonadherence, ABC pathway adherence was associated with a Win Ratio of 1.57 (95% CI: 1.33-1.85; p  < 0.001)., Conclusion:  This Win Ratio analysis demonstrates the significant benefits of NOACs over warfarin and ABC pathway adherence over nonadherence in reducing the composite outcome in patients with AF., Competing Interests: G.Y.H.L.: consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos, and Daiichi-Sankyo. No fees are directly received personally. G.Y.H.L. is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 899871. Other authors hereby declare no personal or professional conflicts of interest relating to any aspect of this particular study., (Thieme. All rights reserved.)

Background: The impact of unhealthy lifestyles on clinical outcomes among patients with atrial fibrillation (AF) who are at low risk of stroke remains uncertain. The study objective was to evaluate the association between unhealthy lifestyles and clinical outcomes among low-risk AF patients with 0-1 non-sex risk factor of the CHA 2 DS 2 -VASc (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, prior Stroke or transient ischemic attack [TIA], Vascular disease, Age 65-74 years, female Sex;) score., Methods: A total of 52,451 low-risk AF patients (mean age 51.6 ± 10.4 years) were evaluated with the National Health Insurance Service of the Republic of Korea database between 2009 and 2016. Using the survey on health habits, an unhealthy lifestyle score (ULS) was calculated by adding one point each if a respondent had a sedentary lifestyle, drinking, or smoking. The primary outcome was the composite of myocardial infarction, ischemic stroke, heart failure, and all-cause death. Multivariable Cox regression analysis was used to estimate the risk of the study outcome according to the ULS., Results: There was a total of 12,792 (24.4%), 24,785 (47.3%), 11,602 (22.1%), and 3272 (6.2%) low-risk AF patients with 0 to 3 points of the ULS, respectively. The median follow-up period was 4.1 (2.1-6.1) years. Compared with the healthiest-lifestyle group (ULS 0), the other groups were associated with significantly higher risks of the primary outcome, with a gradually increasing trend according to the ULS (adjusted hazard ratio [95% confidence interval] =1.17 [1.05-1.31], 1.37 [1.21-1.56], 1.82 [1.53-2.17], for the groups with ULS 1, 2, and 3, respectively)., Conclusion: Unhealthy lifestyles, including a sedentary lifestyle, drinking, and smoking, may synergistically impact poor clinical outcomes in AF patients who are deemed to be at low risk of stroke., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related. Early detection of AF is vital for prevention. While various scores have been developed to predict AF in such a high-risk group, they are yet to incorporated into clinical guidelines. Novel markers and predictors of AF including coronary and intracranial arterial calcification have also been studied. There are also ongoing debates on the management of acute stroke in patients with AF, and those who experienced breakthrough stroke while on oral anticoagulants. We provided an overview of the complex interplay between AF and stroke, as well as the treatment and secondary prevention of stroke in AF. We also comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1-3) and 1 (IQR 0-2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21-2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641-0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377., (© 2023. The Author(s).)

Background: Oral anticoagulation therapy with warfarin or direct oral anticoagulants (DOACs) is the mainstay for stroke prevention in patients with non-valvular atrial fibrillation (AF). The DOACs might have a lower risk of declining renal function than warfarin. This study aimed to compare renal outcomes among rivaroxaban, edoxaban, dabigatran, and warfarin., Method: This cohort study identified 2203 adults with AF who started anticoagulation therapy between 1 July 2013 and 31 December 2020, in a clinical database at a single centre. Inverse probability of treatment weighting was adopted to balance baseline characteristics among four anticoagulants treatment groups. The primary outcome was a composite of cardiac and renal outcomes, involving a ≥30% decline in estimated glomerular filtration rate (eGFR), renal failure and cardiovascular death., Results: After propensity score weighting, dabigatran was associated with significantly lower risks of a ≥30% decline in eGFR (hazard ratio [HR]: .69, 95% confidence interval [CI]: .497-.951, p = .0237), doubling of the serum creatinine level (HR: .49, 95% CI: .259-.927, p = .0282) and the cardiac and renal outcome composite (HR: .67, 95% CI: .485-.913, p = .0115) than warfarin. Rivaroxaban and edoxaban did not show significant protective effects on renal outcomes compared to warfarin., Conclusion: In this study, patients treated with dabigatran had significantly reduced risks of declining renal function and composite cardiac and renal events than those treated with warfarin. However, rivaroxaban and edoxaban were not associated with lower risks of any renal outcomes than warfarin. More studies are warranted to investigate and compare the impact of renal function between different DOACs in patients with AF., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Aims: Chronic obstructive pulmonary disease (COPD) may influence management and prognosis of atrial fibrillation (AF), but this relationship has been scarcely explored in contemporary global cohorts. We aimed to investigate the association between AF and COPD, in relation to treatment patterns and major outcomes., Methods and Results: From the prospective, global GLORIA-AF registry, we analysed factors associated with COPD diagnosis, as well as treatment patterns and risk of major outcomes in relation to COPD. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). A total of 36 263 patients (mean age 70.1 ± 10.5 years, 45.2% females) were included; 2,261 (6.2%) had COPD. The prevalence of COPD was lower in Asia and higher in North America. Age, female sex, smoking, body mass index, and cardiovascular comorbidities were associated with the presence of COPD. Chronic obstructive pulmonary disease was associated with higher use of oral anticoagulant (OAC) [adjusted odds ratio (aOR) and 95% confidence interval (CI): 1.29 (1.13-1.47)] and higher OAC discontinuation [adjusted hazard ratio (aHR) and 95% CI: 1.12 (1.01-1.25)]. Chronic obstructive pulmonary disease was associated with less use of beta-blocker [aOR (95% CI): 0.79 (0.72-0.87)], amiodarone and propafenone, and higher use of digoxin and verapamil/diltiazem. Patients with COPD had a higher hazard of primary composite outcome [aHR (95% CI): 1.78 (1.58-2.00)]; no interaction was observed regarding beta-blocker use. Chronic obstructive pulmonary disease was also associated with all-cause death [aHR (95% CI): 2.01 (1.77-2.28)], MACEs [aHR (95% CI): 1.41 (1.18-1.68)], and major bleeding [aHR (95% CI): 1.48 (1.16-1.88)]., Conclusion: In AF patients, COPD was associated with differences in OAC treatment and use of other drugs; Patients with AF and COPD had worse outcomes, including higher mortality, MACE, and major bleeding., Competing Interests: Conflict of interest: G.F.R. reports consultancy for Boehringer Ingelheim and an educational grant from Anthos, outside the submitted work. No fees are directly received personally. F.F. has received honoraria and support for educational events from Chiesi Ltd. A.B. has been a consultant or speaker for Astra-Zeneca, Bayer, BMS/Pfizer, Medtronic, Vitor Pharma, and Alnylam. G.B. reports small speaker fees from Bayer, Boehringer Ingelheim, Boston, BMS, Daiichi, Sanofi, and Janssen, outside the submitted work. T.-F.C. reported honoraria for lectures from Boehringer Ingelheim, Bayer, Pfizer, and Daiichi Sankyo, outside the submitted work. B.O. has one disclosure AstraZeneca DSMB, Consultant for Boehringer Ingelheim. M.V.H. has been receiving research grants from the Dutch Healthcare Fund, Dutch Heart Foundation, BMS-Pfizer, Bayer Healthcare, and Boehringer Ingelheim and consulting fees from BMS-Pfizer, Bayer Healthcare, and Boehringer Ingelheim to the institution. M.P. is national leader of the AFFIRMO project on multi-morbidity in atrial fibrillation, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 899871. G.Y.H.L. has been consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Anthos, and Daiichi-Sankyo. No fees are directly received personally. All the disclosures happened outside the submitted work. G.Y.H.L. is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator 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. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) [edoxaban 15 mg o.d., dabigatran 110 or 150 o.d., apixaban 2.5 mg o.d., or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or <10 mg o.d.] vs. regular-dosage (RD) NOACs (edoxaban 60/30 mg o.d. or other labeling-dosage NOACs) among a real-world cohort of elderly atrial fibrillation (AF) population similar to the ELDERCARE-AF cohort., Methods and Results: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7294 and 4151 consecutive AF patients aged 80 years or older with a CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack (2 points) score ≥2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from 1 June 2012 to 31 December 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (31 December 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation [hazard ratio (HR): 1.54, 95% confidential interval (CI): 1.09-2.18; P = 0.014), venous thrombosis (HR: 3.75, 95% CI: 1.56-8.97; P = 0.003), and all-cause mortality (HR: 1.21, 95% CI: 1.15-1.29; P <0.001) compared with RD NOACs. VLD NOACs showed worse outcomes in most net clinical outcome (NCO) benefits. The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05)., Conclusion: Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared with that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)