Association of Concomitant Coronary Artery Disease With Cardiovascular Events in Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: Atrial fibrillation (AF) patients often have concomitant coronary artery disease (CAD); however, there are little data on clinical characteristics and outcomes of such patients in daily clinical practice in Japan.Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 4,464 patients, and the median follow up was 5.1 (interquartile range: 2.3-8.0) years. History of CAD was present in 647 patients (14%); of those patients, 267 (41%) had history of myocardial infarction (MI). Patients with CAD were older and had more comorbidities than those without CAD. The crude incidences (% per patient-year) of cardiovascular events were significantly higher in patients with CAD than those without CAD (cardiac death: 1.8 vs. 0.7, stroke or systemic embolism [SE]: 2.9 vs. 2.1, MI: 0.6 vs. 0.1, composite of those events: 5.1 vs. 2.8, respectively, all log-rank P<0.01). After multivariate adjustment, concomitant CAD was associated with incidence of cardiac events, and history of MI was associated with incidence of MI; however, neither history of CAD nor MI was associated with the incidence of stroke/SE. CONCLUSIONS: In Japanese AF patients, concomitant CAD was associated with higher prevalences of major co-morbidities and higher incidences of cardiovascular events; however, history of CAD was not associated with the incidence of stroke/SE.

10-Year Trends of Antithrombotic Therapy Status and Outcomes in Japanese Atrial Fibrillation Patients　- The Fushimi AF Registry.

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 CHADS2score 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, CHADS2score 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.

Characteristics and clinical outcomes in atrial fibrillation patients classified using cluster analysis: the Fushimi AF Registry.

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 < 0.001 and P < 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.

Effectiveness and Safety of Rivaroxaban by General Practitioners　- A Multicenter, Prospective Study in Japanese Patients With Non-Valvular Atrial Fibrillation (GENERAL).

BACKGROUND: Direct oral anticoagulants have become a standard therapy for non-valvular atrial fibrillation (NVAF). However, little is known about their effectiveness/safety when prescribed by general practitioners to treat high-risk populations such as the elderly, those who are frail or have cognitive dysfunction.Methods and Results:In this multicenter, prospective study, a total of 5,717 NVAF patients (mean age 73.9 years) receiving rivaroxaban were registered by general practitioners, with a maximum 3-year follow up (mean 2.0±0.5 years). The primary endpoint was a composite of stroke and systemic embolism (SE). The annual incidence (per 100 person-years) of stroke/SE was 1.23% and for major bleeding, it was 0.63%. Multivariate analyses identified age ≥75 years (hazard ratio [HR]; 2.67, P<0.001) and history of ischemic stroke (HR; 1.89, P=0.005) as significant risk factors of stroke/SE, with history of major bleeding (HR; 14.9, P<0.001) and warfarin use (HR; 2.15, P=0.002) as risk factors for major bleeding events. Neither cognitive dysfunction, defined by the receipt of anti-dementia medications, nor frailty, evaluated by the classification of the Japanese Long-term Care Insurance system, correlated with stroke/SE or major bleeding events. CONCLUSIONS: The low incidence of adverse events, including stroke/SE and bleeding, in patients prescribed rivaroxaban by general practitioners supports its use as a safe and efficacious treatment in the standard clinical care of high-risk patient populations.

Major adverse cardiovascular events and mortality after catheter ablation in Japanese patients with atrial fibrillation: The Fushimi AF Registry.

BACKGROUND: The impact of catheter ablation (CA) on the long-term clinical outcomes in atrial fibrillation (AF) are unclear due to limited cohort investigations. METHODS: The Fushimi AF Registry is a community-based prospective survey of patients with AF in Fushimi-ku, Kyoto, Japan. Of 4465 patients enrolled between March 2011 and July 2019, analyses were performed on 2639 patients (492 patients who underwent CA and 2147 patients who received standard rhythm- and/or rate-control drug therapy at baseline). We compared the baseline characteristics and the incidence of major adverse cardiovascular events (MACE: the composite of cardiovascular death, heart failure hospitalization, myocardial infarction, ischemic stroke or systemic embolism), and all-cause mortality during the follow-up using propensity score matching. RESULTS: After entering 20 covariates in the current matching analysis, 342 patients who underwent CA and 342 matched patients who received drug therapy, with a median follow-up of 1865 days, were included. The patients who underwent CA were significantly associated with lower incidence of MACE (hazard ratio (HR) 0.56, 95% confidential interval (CI) 0.36-0.86; P = 0.0077), and all-cause mortality (HR 0.47, 95% CI 0.29-0.75; P = 0.0016). CONCLUSION: CA was associated with lower incidences of MACE and all-cause mortality for patients with AF as compared with those who received drug therapy. The most common event of MACE in patients who underwent CA was heart failure hospitalization. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000005834.

Different Impact of Resting Heart Rate on Adverse Events in Paroxysmal and Sustained Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: Heart rate (HR) is an important factor in atrial fibrillation (AF); however, it remains unclear whether the impact of HR differs between paroxysmal AF and sustained (persistent and permanent) AF.Methods and Results:The association of resting HR during AF with adverse events (composite of all-cause death, hospitalization for heart failure, stroke/systemic embolisms, myocardial infarction, and arrhythmic events) in 1,064 paroxysmal and 1,610 sustained AF patients from the Fushimi AF Registry were investigated. These patients were divided into 4 groups based on their resting HR; ≥110 beats/min (bpm), 80-109 bpm, 60-79 bpm, and <60 bpm. The number of patients in each group was 486, 400, 172, and 22 for paroxysmal AF, and 205, 734, 645, and 71 for sustained AF, respectively. Among patients with sustained AF, a HR ≥110 bpm was associated with a higher incidence of adverse events at 1 year and during the entire follow up (median of 1,833 days) (hazard ratio [95% confidence interval] compared with a HR of 60-79 bpm: 1.90 [1.31-2.72] at 1 year, 1.38 [1.10-1.72] during the entire follow up). Patients with a HR <60 bpm showed higher incidence of adverse events at 1 year; however, the incidence of adverse events did not differ among all HR groups of paroxysmal AF. CONCLUSIONS: Baseline HR was associated with adverse events in sustained AF, but not in paroxysmal AF.

Impact of Valvular Heart Disease on Mortality, Thromboembolic and Cardiac Events in Japanese Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: There is a growing burden of valvular heart disease (VHD) and atrial fibrillation (AF) due to population aging, but data regarding the characteristics and outcomes of patients with AF and concomitant VHD are lacking.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. Among 3,566 patients with available echocardiographic data, 20% had VHD, consisting of 131 valvular AF (VAF: 3.7%) and 583 nonvalvular AF with VHD (NVAF-VHD: 16.3%). Here, VAF was defined as AF with mitral stenosis or a prosthetic heart valve. AF patients with VHD were older, had more comorbidities with a higher CHADS2 score, and were prescribed oral anticoagulants more frequently than those without VHD. After adjusting for confounders, VHD was not associated with stroke or systemic embolism, all-cause mortality, or cardiac death. NVAF-VHD was significantly associated with an increased risk of hospitalization for heart failure (adjusted hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.16-1.78), whereas VAF was not (HR, 1.28; 95% CI, 0.86-1.92). Among all types of VHD, aortic valve diseases were associated with a higher risk of cardiac events, whereas mitral valve diseases were not. CONCLUSIONS: Although VHD did not significantly affect thromboembolism or mortality, it affected cardiac events depending on type, with aortic valve diseases having higher risk, in Japanese patients with AF.

Treatment for renal anemia and outcomes in non-dialysis patients with chronic kidney disease: the current status of regional medicine according to the Kyoto Fushimi Renal Anemia (KFRA) study.

BACKGROUND: The baseline data obtained in the CKD-JAC demonstrated that insufficient treatment was being provided for renal anemia by institutions specializing in renal disease. The objective of this study was to investigate the status of treatment for renal anemia, including renal/cardiovascular outcomes and mortality, at regional medical facilities since the development of long-acting erythropoiesis-stimulating agents (LA-ESA). METHODS: Non-dialysis outpatients with chronic kidney disease and renal anemia were eligible. Anemia was treated based on the clinical condition of each patient and targeted hemoglobin (Hb) levels. RESULTS: A total of 283 patients from 21 institutions were enrolled and followed up for a maximum of 3 years. A doubling of the serum creatinine level was observed in 89 patients, and renal replacement therapy was initiated in 57 patients. Multivariate Cox regression analysis revealed that a lower mean Hb level (mHb) and receiving fewer frequency of ESA during the follow-up period were independent determinants of the composite renal outcome and overall mortality. During the follow-up period, the percentages of patients with mHb of 10-10.9 g/dL and ≥ 11 g/dL were increased. Similar trends were seen regardless of whether the patients were treated by nephrologists or non-nephrologists. The frequency of ESA treatment was increased among the patients treated by non-nephrologists; however, it was much lower than nephrologists. CONCLUSION: This study demonstrated that, in the era of LA-ESA treatment, higher Hb levels are associated with reduced composite renal outcomes at regional medical facilities. The importance of renal anemia management should be highlighted, even among non-nephrologists.

Progression From Paroxysmal to Sustained Atrial Fibrillation Is Associated With Increased Adverse Events.

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.

Current Status, Time Trends and Outcomes of Combination Therapy With Oral Anticoagulant and Antiplatelet Drug in Patients With Atrial Fibrillation　- The Fushimi AF Registry.

BACKGROUND: The combination of oral anticoagulant (OAC) and antiplatelet drug (APD) increases the bleeding risk in atrial fibrillation (AF). Non-vitamin K antagonist OAC (NOAC) have been increasingly used since 2011. We investigated current status, time trends and outcomes of AF patients using combination therapy in 2011-2017. Methods and Results: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Of 2,378 patients with OAC at enrollment, 521 (22%) received combination therapy, while 1,857 (78%) received OAC alone. When compared with OAC alone, combination therapy patients had more comorbidities, but approximately 30% had no atherosclerotic disease. From 2011 to 2017, the prevalence of combination therapy decreased from 26% to 14%. The prevalence of NOAC increased in those on combination therapy. Off-label under-dosing of NOAC increased year by year, especially in combination therapy. During follow-up, the incidence of major bleeding (hazard ratio [HR], 1.42; 95% CI: 1.03-1.95) and stroke/systemic embolism (HR, 1.48; 95% CI: 1.09-2.00) was higher in the combination therapy than in the OAC alone group. CONCLUSIONS: In Japanese AF patients receiving OAC, the prevalence of combination therapy decreased, with the proportion of NOAC use increasing in 2011-2017. Many patients, however, received off-label NOAC under-dosing, especially in the combination therapy group. Patients with combination therapy had higher incidences of major bleeding as well as stroke/systemic embolism, compared with OAC monotherapy.

Incidence and Risk Factors of Stroke or Systemic Embolism in Patients With Atrial Fibrillation and Heart Failure　- The Fushimi AF Registry.

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome, but the effect of the type and severity of HF on the incidence of stroke or systemic embolism (SE) in atrial fibrillation (AF) patients is unclear.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. Follow-up data were available for 3,749 patients. We defined pre-existing HF as having one of the following: prior hospitalization for HF, presence of HF symptoms (NYHA ≥2), or reduced ejection fraction (<40%). At baseline, 1,008 (26.9%) patients had pre-existing HF. On multivariate analysis, the incidence of stroke/SE was not associated with pre-existing HF (hazard ratio (HR), 1.24; 95% confidence interval (CI), 0.92-1.64) or each criterion for the definition of pre-existing HF, but was associated with high B-type natriuretic peptide (BNP) or N-terminal proBNP levels (above the median of the pre-existing HF group) at baseline (HR, 1.65; 95% CI, 1.06-2.53). Stroke/SE was markedly increased in the initial 30-day period following hospital admission for HF (HR, 12.0; 95% CI, 4.59-31.98). CONCLUSIONS: The effect of HF on the incidence of stroke/SE may depend on the stage or severity of HF in patients with AF. The incidence of stroke/SE was markedly increased in the 30 days after admission for HF, but compensated 'stable' HF did not appear to confer an independent risk.

Correction to: Clinical characteristics and cardiovascular outcomes in patients with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF Registry.

In the original publication of the article, the data of Body mass index ≥ 25 (kg/m2)a is published incorrectly in Table 1. Since this is categorical variable, the data should have been expressed as a number (percentage), not as mean ± standard deviation. The corrected version of Table 1 is as below.

Clinical characteristics and cardiovascular outcomes in patients with atrial fibrillation receiving rhythm-control therapy: the Fushimi AF Registry.

Management of atrial fibrillation (AF) with current rhythm-control therapy has an uncertain impact on outcomes. Among 3731 patients in the Fushimi AF Registry, a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, we investigated the characteristics and outcomes in 478 patients receiving rhythm-control therapy (anti-arrhythmic drug and/or catheter ablation) alone, with 1279 patients receiving rate-control therapy (beta-blockers, calcium channel blockers, and digoxin) alone serving as a reference. The Rhythm-control group, 26% of which had prior catheter ablation, was younger (70.5 ± 10.8 vs. 74.3 ± 10.4 years, P < 0.001) with lower CHA2DS2-VASc score (2.71 ± 1.63 vs. 3.64 ± 1.62, P < 0.001) and received oral anticoagulants less frequently than the Rate-control group. During the median follow-up of 1107 days, the incidence of the composite of cardiac death and heart failure (HF) hospitalization was lower with rhythm control (hazard ratio (HR) 0.24, 95% confidence interval (CI) 0.14-0.36; P < 0.001), whereas that of ischemic stroke/systemic embolism was not significantly different (HR 0.64, 95% CI 0.35-1.10; P = 0.12), when compared to rate control. Propensity score-matching analysis as well as multivariate analysis further supported the relation of Rhythm-control group to the lower incidence of the composite of cardiac death and HF hospitalization. Rhythm-control therapy by anti-arrhythmic drug and/or catheter ablation in the contemporary clinical practice was associated with the lower incidence of the composite of cardiac death and HF hospitalization, as compared with rate-control therapy in a Japanese AF cohort. However, given the fundamental differences in baseline clinical characteristics between the rhythm- and Rate-control groups, the results cannot be generalizable.

Current Status and Outcomes of Direct Oral Anticoagulant Use in Real-World Atrial Fibrillation Patients　- Fushimi AF Registry.

BACKGROUND: The current status and outcomes of direct oral anticoagulant (DOAC) use have not been widely evaluated in unselected patients with atrial fibrillation (AF) in the real world.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions (n=80) in Fushimi, Kyoto, Japan. Follow-up data with oral anticoagulant (OAC) status were available for 3,731 patients by the end of November 2015. We evaluated OAC status and clinical outcomes according to OAC status. The number (incidence rate) of stroke/systemic embolism (SE) and major bleeding events during the median follow-up of 3.0 years was 224 (2.3%/year) and 177 (1.8%/year), respectively. After the release of DOAC, the prevalence of DOAC use increased gradually and steadily, and that of warfarin, DOAC and no OAC was 37%, 26% and 36%, respectively in 2015. On Cox proportional hazards modeling incorporating change in OAC status as a time-dependent covariate for stroke/SE and major bleeding events, use of DOAC compared with warfarin was not associated with stroke/SE events (HR, 0.95; 95% CI: 0.59-1.51, P=0.82) or major bleeding events (HR, 0.82; 95% CI: 0.50-1.36, P=0.45). CONCLUSIONS: In real-world clinical practice, there were no significant differences in stroke/SE events or major bleeding events for DOAC compared with warfarin in patients with AF.

Sex-Related Differences in the Clinical Events of Patients With Atrial Fibrillation　- The Fushimi AF Registry.

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.Methods and Results:The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto. Follow-up data were available for 3,878 patients. Female AF patients (n=1,551, 40.0%) were older (77.0 vs. 71.4 years; P<0.001) than male patients (n=2,327, 60.0%). Female patients were more likely to have heart failure (31.1% vs. 23.7%; P<0.001). Previous stroke incidence (19.2% vs. 21.4%; P=0.083) was comparable between male and female patients. During the median follow-up period of 1,102 days, Cox regression analysis demonstrated that female sex was not independently associated with a risk of stroke or systemic embolism (adjusted hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.54-1.00, P=0.051). However, female sex showed an association with a lower risk of intracranial hemorrhage (adjusted HR 0.54; 95% CI: 0.30-0.95, P=0.032) and all-cause death (adjusted HR 0.56; 95% CI: 0.46-0.68, P<0.001). CONCLUSIONS: We demonstrated that female sex is not independently associated with an increased risk of thromboembolism, but is associated with a decreased risk of intracranial hemorrhage and all-cause death in Japanese AF patients enrolled in the Fushimi AF Registry.

Incidence of Stroke or Systemic Embolism in Paroxysmal Versus Sustained Atrial Fibrillation: The Fushimi Atrial Fibrillation Registry.

BACKGROUND AND PURPOSE: There is controversy on the relationship of the type of atrial fibrillation (AF) to stroke. Although several studies show that patients with paroxysmal AF (PAF) have a stroke risk similar to those with persistent or permanent AF, recent studies suggest that PAF is associated with a lower rate of stroke. Limited data on stroke risk associated with PAF are evident in Asian populations. METHODS: The Registry Study of Atrial Fibrillation Patients in Fushimi-ku (Fushimi AF Registry) is a community-based survey of patients with AF in Fushimi-ku, Kyoto, Japan. Patients were categorized into 2 types of AF: PAF or sustained (persistent or permanent) AF. We compared clinical events between PAF (n=1588) and sustained AF (n=1716). RESULTS: Patients with PAF were younger, had less comorbidities, and received oral anticoagulants (OAC) less commonly. A lower risk of stroke/systemic embolism during follow-up period in the patients with PAF was consistently observed (non-OAC users: hazard ratio, 0.45; 95% confidence intervals, 0.27-0.75; P<0.01 and OAC users: hazard ratio, 0.59; 95% confidence interval, 0.35-0.93; P=0.03). The composite end point of stroke/systemic embolism/all-cause mortality was also lower in PAF, whether among OAC users (hazard ratio, 0.77; 95% confidence interval, 0.59-0.99; P=0.046) or non-OAC users (hazard ratio, 0.59; 95% confidence interval, 0.46-0.75; P<0.01). On multivariate analysis, PAF was an independent predictor of lower stroke/systemic embolism risk. CONCLUSIONS: In this large cohort of Japanese patients with AF, PAF was independently associated with lower incidence of stroke/systemic embolism than sustained AF. This may aid decision making for anticoagulation, especially in those patients with AF with few stroke risk factors. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834.

Low Body Weight Is Associated With the Incidence of Stroke in Atrial Fibrillation Patients - Insight From the Fushimi AF Registry.

BACKGROUND: Japanese patients with atrial fibrillation (AF) are generally small and lean, but knowledge of the clinical characteristics of those with low body weight (LBW: ≤50 kg) is limited. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions in Fushmi-ku, Japan. The BW and follow-up data were available for 2,945 patients. We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group. Patients in the LBW group accounted for 26.8% (788 patients) of the total. The LBW group was more often female, older, and had higher CHADS2score. The incidence of stroke/systemic embolism (SE) during follow-up was higher in the LBW group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.57-3.04; P<0.01), whereas that of major bleeding was comparable (HR: 1.05, 95% CI: 0.64-1.68; P=0.84). This trend was consistently observed in the subgroups stratified by age, sex, and oral anticoagulant prescription at baseline. Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE. CONCLUSIONS: Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE, but the incidence of major bleeding was not particularly high.

Inappropriate use of oral anticoagulants for patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmic disorder among the elderly, and increases the risk of stroke. Oral anticoagulants (OAC) are highly effective in preventing stroke, and there are evidence-based guidelines for the optimal use of OAC in patients with AF. METHODS AND RESULTS: The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, a typical urban community in Japan with a total population of 283,000. Of the 3,282 patients enrolled by October 2012, 1-year follow-up was completed for 2,914 patients. OAC, mainly warfarin, were given to 1,546 patients (53.1%); overused for low-risk patients, and underused for patients at risk, based on the guidelines. Moreover, warfarin was sometimes given at a sub-therapeutic dose; only 54.4% of patients were within the optimal therapeutic range. The 1-year outcomes revealed that the incidences of both stroke and major bleeding were equivalent between patients taking OAC and those without; major clinical events were as follows: (OAC vs. non-OAC) stroke 2.7% vs. 2.8%, ischemic stroke 2.1% vs. 2.0% and major bleeding 1.4% vs. 1.5% (NS for all). CONCLUSIONS: The Fushimi AF Registry provides a unique snapshot of current AF management in an urban community in Japan. The present study reveals inappropriate use of OAC for patients with AF, indicating discordance between guideline recommendations and real-world clinical practice.

Observational study of frailty in older Japanese patients with non-valvular atrial fibrillation receiving anticoagulation therapy.

The number of patients with atrial fibrillation is increasing, and frailty prevalence increases with age, posing challenges for physicians in prescribing anticoagulants to such patients because of possible harm. The effects of frailty on anticoagulant therapy in older Japanese patients with nonvalvular atrial fibrillation (NVAF) are unclear. Herein, we prescribed rivaroxaban to Japanese patients with NVAF and monitored for a mean of 2.0 years. The primary endpoint was stroke or systemic embolism. The secondary endpoints were all-cause or cardiovascular death, composite endpoint, and major or non-major bleeding. Frailty was assessed using the Japanese long-term care insurance system. A multiple imputation technique was used for missing data. The propensity score (PS) was obtained to estimate the treatment effect of frailty and was used to create two PS-matched groups. Overall, 5717 older patients had NVAF (mean age: 73.9 years), 485 (8.5%) were classified as frail. After PS matching, background characteristics were well-balanced between the groups. Rivaroxaban dosages were 10 and 15 mg/day for approximately 80% and the remaining patients, respectively. Frailty was not associated with the primary endpoint or secondary endpoints. In conclusion, frailty does not affect the effectiveness or safety of rivaroxaban anticoagulant therapy in older Japanese patients with NVAF.Trial registration: UMIN000019135, NCT02633982.

Association of Regression from Sustained to Paroxysmal Atrial Fibrillation With Clinical Outcomes: The Fushimi AF Registry.

In some cases, albeit infrequently, patients with atrial fibrillation (AF) may experience a regression from a sustained to a paroxysmal type. We sought to investigate how regression of AF is associated with outcomes. Among the patients with AF enrolled in the Fushimi AF Registry who were identified as having sustained AF at baseline, conversion of sustained to paroxysmal AF during follow-up was defined as AF regression. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiac death, myocardial infarction, ischemic stroke, systemic embolism, or hospitalization due to heart failure. Among 2,261 patients with sustained AF at baseline, AF regression was observed in 214 (9.5%) patients over a median follow-up period of 5.8 years (1.78% per patient-year). The annual incidence of MACE was significantly lower in patients with AF regression than in those without (3.47% vs 6.59% per patient-year, p <0.001, adjusted hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.38 to 0.72). Furthermore, AF regression was significantly associated with reduced risk of MACE during and after the regression period from sustained to paroxysmal forms (during the regression period: adjusted HR 0.45, 95% CI 0.22 to 0.90; after the regression period: adjusted HR 0.43, 95% CI 0.26 to 0.67). The incidence of MACE was comparable between spontaneous regression (35/178: 19.7%) and therapy-associated regression (either receiving catheter ablation or antiarrhythmic drugs before the regression) (7/36: 19.4%) (p = 0.98). Regression of AF was associated with lower incidence of adverse cardiovascular events. The risk of adverse events decreased significantly during the regression period, and this reduced risk persisted after regression. Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000005834.