Hisashi Ogawa

Incidence of Ischemic Stroke in Japanese Patients With Atrial Fibrillation Not Receiving Anticoagulation Therapy

BACKGROUNDnThe incidence rate of ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients without anticoagulation therapy remains unclear.nnnMETHODS AND RESULTSnWe performed a pooled analysis of 3,588 patients from the Shinken Database (n=1,099), J-RHYTHM Registry (n=1,002), and Fushimi AF Registry (n=1,487) to determine the incidence rate of ischemic stroke in Japanese NVAF patients without anticoagulation therapy. Average patient age was 68.1 years. During the follow-up period (total, 5,188 person-years; average, 1.4 years), 69 patients suffered from ischemic stroke (13.3 per 1,000 person-years; 95% confidence intervals [CI]: 10.5-16.8). The incidence rates of ischemic stroke were 5.4, 9.3, and 24.7 per 1,000 person-years and 5.3, 5.5, and 18.4 per 1,000 person-years in patients with low (0), intermediate (1), and high (≥ 2) CHADS2 and CHA2DS2-VASc scores, respectively. History of ischemic stroke or transient ischemic attack (hazard ratio [HR], 3.25; 95% CI: 1.86-5.67), age ≥ 75 years (HR, 2.31; 95% CI: 1.18-4.52), and hypertension (HR, 1.69; 95% CI: 1.01-2.86) were independent risk factors for ischemic stroke.nnnCONCLUSIONSnA low incidence rate of ischemic stroke was observed in Japanese NVAF patients except for those with CHADS2 score ≥ 2. In this pooled analysis, history of ischemic stroke or transient ischemic attack, advanced age, and hypertension were identified as independent risk factors for ischemic stroke.

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 –

BACKGROUNDnJapanese 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.nnnMETHODS AND RESULTSnThe 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.nnnCONCLUSIONSnPatients 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.

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

BACKGROUNDnThe 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.Methodsu2004andu2004Results: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).nnnCONCLUSIONSnIn 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.

Left atrial enlargement is an independent predictor of stroke and systemic embolism in patients with non-valvular atrial fibrillation

Controversy exists regarding whether left atrial enlargement (LAE) is a predictor of stroke/systemic embolism (SE) in atrial fibrillation (AF) patients. The Fushimi AF Registry, a community-based prospective survey, enrolled all AF patients in Fushmi-ku, Japan, from March 2011. Follow-up data and baseline echocardiographic data were available for 2,713 patients by August 2015. We compared backgrounds and incidence of events over a median follow-up of 976.5 days between patients with LAE (left atrial diameteru2009>u200945u2009mm; LAE group) and those without in the Fushimi AF Registry. The LAE group accounted for 39% (nu2009=u20091,049) of cohort. The LAE group was older and had longer AF duration, with more prevalent non-paroxysmal AF, higher CHADS2/CHA2DS2-VASc score, and oral anticoagulant (OAC) use. A higher risk of stroke/SE during follow-up in the LAE group was found (entire cohort; hazard ratio (HR): 1.92, 95% confidence interval (CI): 1.40–2.64; pu2009<u20090.01; without OAC; HR: 1.97, 95% CI: 1.18–3.25; pu2009<u20090.01; with OAC; HR: 1.83, 95% CI: 1.21–2.82; pu2009<u20090.01). LAE was independently associated with increased risk of stroke/SE (HR: 1.74, 95% CI: 1.25–2.42; pu2009<u20090.01) after adjustment by the components of CHA2DS2-VASc score and OAC use. In conclusion, LAE was an independent predictor of stroke/SE in large community cohort of AF patients.

Incidence and predictors of ischemic stroke during hospitalization for congestive heart failure.

Heart failure (HF) increases the risk of ischemic stroke. Data regarding the incidence and predictors of ischemic stroke during hospitalization for HF are limited. The study population of this retrospective cohort study consisted of patients with congestive HF, consecutively admitted to our center from October 2010 to April 2014. We excluded patients complicated with acute myocardial infarction, infective endocarditis, and takotsubo cardiomyopathy. We also excluded those with dialysis or mechanical circulatory support. We investigated the incidence of ischemic stroke during hospitalization for HF. Thereafter, we divided the patients without oral anticoagulants at admission into two groups: patients with ischemic stroke and those without it, and explored the predictors of ischemic stroke. A total of 558 patients (287 without atrial fibrillation (AF), 271 with AF) were enrolled. The mean age was 76.8xa0±xa012.3xa0years, and 244 patients (44xa0%) were female. The mean left-ventricular ejection fraction was 47.4xa0%. Oral anticoagulants were prescribed in 147 patients (8 without AF, 139 with AF). During hospitalization (median length 18xa0days), symptomatic ischemic stroke (excluding catheter-related) occurred in 15 patients (2.7xa0% of the total, 8 without AF, 7 with AF). Predictors significantly associated with increased risk of ischemic stroke in patients without oral anticoagulants were as follows; short-term increases in blood urea nitrogen after admission (at day 3; odds ratio (per 1 md/dl): 1.06, 95xa0% confidence interval (CI) 1.01–1.11, pxa0=xa00.02, and at day 7; odds ratio: 1.03, 95xa0% CI 1.00–1.07, pxa0=xa00.03, respectively), and previous stroke (odds ratio; 3.33, 95xa0% CI 1.01–11.00, pxa0=xa00.04). The incidence of ischemic stroke during hospitalization for HF was high, even in patients without AF. Previous stroke and short-term increases in blood urea nitrogen was significantly associated with the incidence of ischemic stroke.

Stroke and death in elderly patients with atrial fibrillation in Japan compared with the United Kingdom

Background Data on stroke, mortality and associated comorbidities in elderly patients with atrial fibrillation (AF) in Japan may differ from Western countries. There have been few systematic comparisons between stroke risk profiles and outcomes among community-based elderly (aged ≥75 years) patients with AF in Japan and the UK. Objective and methods We compared clinical characteristics, stroke risk and outcomes among elderly patients with AF from the Fushimi AF Registry (Japan; N=1791) and the Darlington AF Registry (UK; N=1338). Results The Fushimi cohort had a mean age 81.8 (standard deviation (SD) 5.3) years and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75u2005years (double), diabetes mellitus, previous thromboembolism (double), vascular disease, age 65–74u2005years and female gender) score 4.3 (1.4), whereas the Darlington cohort had a mean age 83.6 (5.7) years and CHA2DS2-VASc score 4.4 (1.4). Over a 12-month follow-up period, observed stroke and mortality rates in Fushimi were 3.4% (n=61) and 11.5% (n=206), while corresponding event rates in the Darlington cohort were 4.4% (n=59) and 14.1% (n=188), respectively. Appropriate use of oral anticoagulation (OAC, essentially a vitamin K antagonist) was <60% in both registries. On multivariable analysis, ethnicity (Japan vs UK) was neither associated with the risk of stroke (OR 0.92, 95% CI 0.63 to 1.36; p=0.69) nor death (OR 0.92, 95% CI 0.80 to 1.27; p=0.92). In a subgroup analysis of elderly patients not receiving OAC (n=1489), a history of stroke was associated with the risk of stroke (OR 2.42, 95% CI 1.39 to 4.12; p=0.002), but not ethnicity (OR 0.86, 95% CI 0.50 to 1.47; p=0.58). Conclusions Elderly (age ≥75 years) patients with AF in both Japan and the UK are at similarly high risk of stroke and death, with OAC still underused in both populations. Ethnicity was not independently associated with the risk of stroke, regardless of OAC use or non-use.

Relation of Stroke and Major Bleeding to Creatinine Clearance in Patients With Atrial Fibrillation (from the Fushimi AF Registry)

Creatinine clearance (CrCl) has been widely used to adjust the dosage of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation (AF) and exclude contraindicated patients. However, there are few available real-world data on the relation between CrCl and adverse clinical outcomes in patients with AF. Therefore, we evaluated the clinical characteristics and adverse events in Japanese patients with AF stratified by CrCl. We categorized patients in the Fushimi AF Registry, a large prospective community-based Japanese cohort of patients with AF, into 3 groups as follows: (1) CrCl <30xa0ml/min, (2) CrCl 30 to 49xa0ml/min, and (3) CrCl ≥50xa0ml/min. We evaluated 3,080 patients after a median follow-up of 1,076xa0days. Comparing with patients with CrCl ≥50xa0ml/min, patients with AF with CrCl <30xa0ml/min showed increased risks of stroke/systemic embolism (SE) (hazard ratio [HR] 1.68; 95% confidence interval [CI] 1.04 to 2.65; pxa0= 0.04) and major bleeding (HR, 2.08; 95% CI 1.23 to 3.39; pxa0= 0.008) after adjustment for prespecified factors. Patients with AF with CrCl <30xa0ml/min were also associated with higher risks of all-cause death, hospitalization for heart failure, myocardial infarction, or the composite of all-cause death and stroke/SE. However, no excess risk of stroke/SE (HR 1.10; 95% CI 0.76 to 1.58; pxa0= 0.6) or major bleeding (HR 0.98; 95% CI 0.63 to 1.48; pxa0= 0.9) was noted for patients with CrCl 30 to 49xa0ml/min. In conclusion, Japanese patients with AF with CrCl <30xa0ml/min were closely associated with adverse clinical events including stroke/SE and major bleeding.

Thyroid Storm with Heart Failure Treated with a Short-acting Beta-adrenoreceptor Blocker, Landiolol Hydrochloride.

Beta-adrenoreceptor blockers are essential in controlling the peripheral actions of thyroid hormones and a rapid heart rate in patients with thyroid storm, although they should be used with great caution when there is the potential for heart failure. A 67-year-old woman was diagnosed as having thyroid storm in addition to marked tachycardia with atrial fibrillation and heart failure associated with a reduced left ventricular function. The administration of an oral beta blocker, bisoprolol fumarate, induced hypotension and was not tolerable for the patient, whereas landiolol hydrochloride, a short-acting intravenous beta-adrenoreceptor blocker with high cardioselectivity and a short elimination half-life, was useful for controlling the patients tachycardia and heart failure without causing hemodynamic deterioration.

Clinical characteristics and outcomes of dialysis patients with atrial fibrillation: the Fushimi AF Registry.

Atrial fibrillation (AF) is common in dialysis patients. However, clinical characteristics and outcomes of dialysis patients with AF are poorly understood. The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available for 3713 patients with a median follow-up of 2.8xa0years. We compared clinical characteristics and outcomes between the dialysis group (nxa0=xa092; 2.5xa0%) and others. The dialysis group had more various co-morbidities, with a mean CHADS2 score of 2.5, and the rate of warfarin prescription was 38xa0%. The annual incidence rates of stroke or systemic embolism (SE), major bleeding, and all-cause death in the dialysis group were 4.0, 5.1, and 20.9 per 100xa0person-years, respectively. There was no significant difference in the incidence rate of stroke/SE between the dialysis group and the non-dialysis group [hazard ratio (HR) 1.74 (95xa0% confidence interval (CI) 0.74–3.42)]. The incidence rates of major bleeding, all-cause death, and the composite of stroke/SE and all-cause death in the dialysis group were higher than those in the non-dialysis group [major bleeding: HR 3.09 (95xa0% CI 1.46–5.72), all-cause death: HR 3.51 (95xa0% CI 2.48–4.81), the composite of stroke/SE and all-cause death: HR 2.99 (95xa0% CI 2.15–4.05)]. Among dialysis patients, warfarin did not affect major clinical events including stroke/SE, bleeding or all-cause death. Among AF patients, those receiving dialysis showed higher incidence of major bleeding and all-cause death compared with non-dialysis patients, but the risk of stroke/SE was not particularly high.Clinical trial registrationURL: http://www.umin.ac.jp/ctr/index.htm.