Background and Purpose— Atrial fibrillation (AF) is a common arrhythmic disorder among the elderly and sometimes progresses from paroxysmal to sustained (persistent or permanent) types. Clinical outcomes of patients with progression of AF were unknown. This study assessed the characteristics of patients with AF progression and the impact of AF progression on various clinical events. Methods— The Fushimi AF Registry is a community-based prospective survey of the patients with AF in Fushimi-ku, Kyoto. Analyses were performed on 4045 patients, which included 1974 paroxysmal AF (PAF; 48.8%) and 2071 sustained (persistent or permanent) AF (SAF; 51.2%) at baseline. Results— During the median follow-up period of 1105 days, progression of AF occurred in 252 patients with PAF (4.22 per 100 person-years). Multivariate Cox regression analysis demonstrated that progression of AF was significantly associated with an increased risk of ischemic stroke or systemic embolism (adjusted hazard ratio [HR], 4.10; 95% CI, 1.95–8.24; P <0.001 [versus PAF without progression]; adjusted HR, 2.20; 95% CI, 1.11–4.00; P =0.025 [versus SAF]) during progression period from paroxysmal to sustained forms. The risk after the progression was equivalent to SAF (adjusted HR, 1.54; 95% CI, 0.78–2.75; P =0.201 [versus SAF]). AF progression was significantly associated with a higher risk of hospitalization for heart failure (adjusted HR, 2.70; 95% CI, 1.55–4.52; P <0.001 [versus PAF without progression]; adjusted HR, 1.81; 95% CI, 1.08–2.88; P =0.026 [versus SAF]). Conclusions— Progression of AF was associated with increased risk of clinical adverse events during arrhythmia progression period from PAF to SAF among Japanese patients with AF. The risk of adverse events was transiently elevated during progression period from PAF to SAF and declined to the level equivalent to SAF after the progression. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000005834.

ies have reported conflicting results. 12, 13 In Japanese patients with AF, the J-RHYTHM registry concluded that female sex was not an independent risk factor for thromboembolic events and that male sex was a risk factor for major bleeding and all-cause death. 14 In addition, they validated that the 'CHA2DS2-VA score', excluding female sex, was performed similarly for risk stratification for thromboembolic events. 15 However, a Taiwanese study indicated that females had a higher rate of ischemic stroke than males among patients with AF who were not taking anticoagulants and aged <65 years. 16 In a Chinese AF A trial fibrillation (AF) is the most common cardiac arrhythmia and increases the risk of ischemic stroke and death. 1,2 Previous studies have indicated sex-related differences in the clinical characteristics and outcomes of AF patients. 3-6 Female sex is considered an increased risk for thromboembolism in patients with AF, albeit with an age-dependency (being relevant at age ≥65 or with other risk factors) and is included in the CHA2DS2-VASc score for stroke risk stratification. 7-10 A recent Swedish study also demonstrated that female AF patients aged ≥75 years are at higher risk of ischemic stroke, 11 but other stud- Background: Female sex is considered a risk factor for thromboembolism in patients with atrial fibrillation (AF), and is included in the risk stratification scheme, CHA2DS2-VASc score. The purpose of the present study was to investigate the clinical outcomes of female Japanese AF patients.

Aims The risk of adverse events in atrial fibrillation (AF) patients was commonly stratified by risk factors or clinical risk scores. Risk factors often do not occur in isolation and are often found in multimorbidity ‘clusters’ which may have prognostic implications. We aimed to perform cluster analysis in a cohort of AF patients and to assess the outcomes and prognostic implications of the identified comorbidity cluster phenotypes. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Hierarchical cluster analysis was performed on 4304 patients (mean age: 73.6 years, female; 40.3%, mean CHA2DS2-VASc score 3.37 ± 1.69), using 42 baseline clinical characteristics. On hierarchical cluster analysis, AF patients could be categorized into six statistically driven comorbidity clusters: (i) younger ages (mean age: 48.3 years) with low prevalence of risk factors and comorbidities (n = 209); (ii) elderly (mean age: 74.0 years) with low prevalence of risk factors and comorbidities (n = 1301); (iii) those with high prevalence of atherosclerotic risk factors, but without atherosclerotic disease (n = 1411); (iv) those with atherosclerotic comorbidities (n = 440); (v) those with history of any-cause stroke (n = 681); and (vi) the very elderly (mean age: 83.4 years) (n = 262). Rates of all-cause mortality and major adverse cardiovascular or neurological events can be stratified by these six identified clusters (log-rank test; P &lt; 0.001 and P &lt; 0.001, respectively). Conclusions We identified six clinically relevant phenotypes of AF patients on cluster analysis. These phenotypes can be associated with various types of comorbidities and associated with the incidence of clinical outcomes. Clinical Trial Registration Information https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.

Background: Atrial fibrillation (AF) increases the risk of stroke and death. Oral anticoagulants (OAC) are highly effective in reducing the risk of stroke, and direct oral anticoagulants (DOAC) became available worldwide in 2011. Methods and Results:The Fushimi AF Registry is an on-going prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. The study cohort consisted of 4,489 patients (mean age 73.6 years, 59.6% male, mean CHADS2 score 2.03), enrolled in 2011-2017. From 2011 to 2021, antithrombotic therapy has undergone a major transition; the proportion of patients receiving OAC has increased from 53% to 70%, with a steady uptake of DOAC (from 2% to 52%), whereas the proportion of patients receiving antiplatelet agents has decreased from 32% to 14%. Over a median follow-up of 5.1 years, the incidence of stroke/systemic embolism (SE), major bleeding, and all-cause death was 2.2%, 1.9%, and 4.9% per patient-year, respectively. The incidence of stroke/SE (1.6% vs. 2.3%; P<0.01), major bleeding (1.6% vs. 2.0%; P=0.07), and death (4.2% vs. 5.0%; P<0.01) was lower among patients enrolled in 2014-2017 than in 2011-2013, despite comparable baseline characteristics (age 73.2 vs. 73.7 years, CHADS2 score 2.03 vs. 2.04, and HAS-BLED score 1.67 vs. 1.77, respectively). Conclusions:Over the past 10 years, there has been a major transition in antithrombotic therapy and a decline in the incidence of adverse events in AF patients.

PCI) in patients requiring OAC, triple therapy (OAC plus dual APD) was inferior to double therapy (OAC plus single APD) in a randomized trial in patients receiving warfarin. 7 In AF patients receiving a combination of non-vitamin K antagonist OAC (NOAC) and single APD, bleeding risk was reduced compared with conventional triple therapy (warfarin plus dual APD). 8,9 Beyond 1 year, current European guidelines recommend OAC monotherapy for AF patients with stable vascular disease. 10 There is no evidence, however, based on randomized controlled trials regarding OAC S troke prevention is central to the management of atrial fibrillation (AF), and oral anticoagulants (OAC) are recommended in guidelines to reduce the risk of ischemic stroke and mortality. 1 Many AF patients have concomitant atherosclerotic disease such as coronary artery disease (CAD) and peripheral artery disease (PAD). 2,3 Therefore, the combination of OAC and antiplatelet drugs (APD) is often prescribed, although this is likely to increase the risk of bleeding. 4-6 In the 1 year after percutaneous coronary intervention

Background Oral anticoagulants reduce the risk of ischaemic stroke, but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and Results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4,304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1,307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; p &lt; 0.01). They were more likely to have pre-existing heart failure (33.7% vs 26.7%; p &lt; 0.01), history of major bleeding (7.7% vs. 4.0%; p &lt; 0.01) and higher mean HAS-BLED score (2.05 vs.1.73; p &lt; 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 (95% confidence interval [CI], 1.06-3.23; p = 0.03). All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding (HR 2.73 [95% CI, 2.16-3.41; p &lt; 0.01]). Conclusion In this community based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients.

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