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Although some sex differences in stroke have been reported, differences in the effects of antiplatelet therapy for secondary stroke prevention have not been clarified.In the Cilostazol Stroke Prevention Study combination trial, patients with high-risk, non-cardioembolic ischemic stroke between 8 and 180 days after onset treated with aspirin or clopidogrel alone were recruited and randomly assigned to receive either monotherapy or dual antiplatelet therapy (DAPT) using cilostazol and followed up for 0.5-3.5 years. The primary efficacy outcome was recurrence of ischemic stroke. The safety outcome was severe or life-threatening hemorrhage. Outcomes were analyzed by sex.A total of 1,320 male patients and 558 female patients were included. The male patients had more risk factors than the female patients. In male patients, the primary endpoint occurred at a rate of 2.0 per 100-patient years in the DAPT group and 5.1 per 100 patient-years in the monotherapy group (hazard ratio (HR), 0.40; 95% confidence interval (CI), 0.23-0.68). In male patients, DAPT prolonged the time to recurrent stroke by 4.02-fold (95% CI, 1.63-9.96) compared with monotherapy. In female patients, the average annual event rates were 2.7 per 100 patient-years in the DAPT group and 3.3 per 100 patient-years in the monotherapy group (HR, 0.82; 95% CI, 0.37-1.84). Safety outcomes did not differ significantly in both male and female patients.Long-term DAPT using cilostazol reduced the recurrence of ischemic stroke and prolonged the recurrence-free time in male patients, but not in female patients.

BACKGROUND The effects of catheter ablation (CA) energy sources on myocardial injury and coagulation biomarkers among Japanese non-valvular atrial fibrillation patients receiving uninterrupted periprocedural edoxaban are unclear. This KYU-RABLE exploratory subanalysis compared the effects of CA using radiofrequency energy vs. cryoballoon on: (1) myocardial injury; and (2) plasma edoxaban and coagulation biomarker concentrations measured before and after CA.Methods and Results:Plasma creatine kinase (CK), edoxaban, D-dimer, and prothrombin fragment 1+2 (F1+2) concentrations within 1 h before CA were compared with concentrations the day after. All biomarkers increased after CA, regardless of the energy source, but especially with cryoballoon. Significantly higher increases in CK concentrations from before to the day after CA were seen with cryoballoon compared with radiofrequency energy (P

Supplemental Digital Content is available in the text., Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000012180.

Objectives. A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the E -wave to E ′ ratio ( E / E ′ ) using transthoracic echocardiography (TTE), and (2) whether E / E ′ contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). Methods. Patients with type 2 diabetes and left ventricular ejection fraction LVEF ≥ 40 % without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal E / E ′ ≥ 13.0 . Results. Thirty-one patients were analyzed. BNP and E / E ′ improved, with BNP levels declining from 36.8 ± 30.5 pg / mL to 26.3 ± 25.9 pg / mL ( p = 0.0014 ) and E / E ′ dropping from 12.7 ± 4.7 to 11.0 ± 3.3 ( p = 0.0376 ). The LVEF showed no significant changes. E / E ′ improved only in patients with E / E ′ ≥ 13.0 . Favorable changes in E / E ′ were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and ∆ E / E ′ /∆BMI contributed to ∆BNP/baseline BNP ( p = 0.0075 , R 2 = 0.49264 ). Conclusions. Liraglutide had favorable effects on BNP and E / E ′ but not on LVEF. E / E ′ improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of E / E ′ . The BMI-adjusted E / E ′ significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565.

Aims/Introduction Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients. Materials and Methods Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets−; 103 participants); diabetes mellitus− MetS+ (133 participants); and diabetes mellitus− MetS− (302 participants). fQRS was assessed using the results of electrocardiography. Results The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS− (35%), than those with diabetes mellitus− MetS+ (14%) or diabetes mellitus− MetS− (10%; P, Fragmented QRS was observed more frequently in patients with diabetes mellitus than in metabolic syndrome and control individuals. Diabetes mellitus was the most significant determinant for fragmented QRS among metabolic syndrome and other traditional metabolic risk factors.

Background: The Foods with Function Claims (FFC) was introduced in Japan in April 2015 to make more products available that are labeled with health functions. The products’ functionality of function claims must be explained by scientific evidence presented in systematic reviews (SRs), but the quality of recent SRs is unclear. This study assessed the quality of SRs in the FFC registered on the Consumer Affairs Agency (CAA) website in Japan. Methods: We searched the database from 1 April to 31 October 2022. Confidence in the methodological quality of each SR was evaluated by the AMSTAR 2 checklist. Results: Forty SRs were randomly extracted on the basis of the eligibility criteria and recruitment procedures. Overall confidence was rated as “high” (N = 0, 0%), “moderate” (N = 0, 0%), “low” (N = 2, 5%), or “critically low” (N = 38, 95%). The mean AMSTAR 2 score was 51.1% (SD 12.1%; range 19–73%). Among the 40 SRs, the number of critical domain deficiencies was 4 in 7.5% of SRs, 3 in 52.5% of SRs, 2 in 35% of SRs, and 1 in 5% of SRs. Registering the review’s protocol and comprehensive search strategies were particularly common deficiencies. Additionally, the risk of bias (RoB) was insufficiently considered. Conclusion: Overall, the methodological quality of the SRs based on the FFC, introduced eight years earlier, was very poor. This was especially true in the interpretation and discussion of critical domains, which had many deficiencies in terms of protocol registration, a comprehensive literature search strategy, and accounting for the RoB.

Objective We provided diagnostic and therapeutic strategies for Meniere's disease in accordance with Japanese Clinical Practice Guideline of Meniere's disease and delayed endolymphatic hydrops 2nd ed. Tokyo: Kanehara Shuppan; 2020 edited by the Japan Society for Equilibrium Research. Methods The Committee for Clinical Practice Guidelines was entrusted with a review of the scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment for Meniere's disease were produced, and the literature according to each of them including CQ was searched. The recommendations are based on the literature review and the expert opinion of a subcommittee. Results Diagnosis criteria of Meniere's disease are classified into Meniere's disease with typical cochlear and vestibular symptoms, and atypical Meniere's disease with either cochlear symptoms or vestibular symptoms. Treatment of Meniere's disease was composed of lifestyle changes, medications such as anti-vertigo drugs and diuretics, middle ear positive pressure treatment, and selective destruction of the vestibule. Conclusion Meniere's disease is diagnosed based on clinical histories and examination findings after processes of differential diagnosis. Treatment option of the disease should be selected in order of invasiveness, according to the severity of the disease and the response to each treatment.

We conducted a multicenter, randomized, double‐blind, placebo‐controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end‐stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK‐100STP (120 μg and 240 μg) with placebo in patients with non‐diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK‐100STP over placebo was not observed. A prior phase II study on which the Phase IIb/III study design was based included only Japanese patients. We therefore evaluated TRK‐100STP efficacy and safety in a subgroup of Japanese patients using the CASSIOPEIR dataset. As the timing of treatment initiation is important in CKD, we conducted additional subgroup analyses based on the baseline serum creatinine (SCr) and eGFR. ITT analysis was performed in a Japanese subgroup (n = 339) in which the primary endpoint was the first occurrence of renal composite endpoint. Significant differences were observed for TRK‐100STP 240 μg vs. placebo (P = 0.0493; HR 0.69 [95% CI: 0.47, 1.00]), but no significant difference was observed between TRK‐100 120 μg and placebo (P = 0.3523; HR 0.85). More prominent improvement was observed with TRK‐100STP 240 μg vs. placebo for baseline SCr

Although time in target range (TTR) of systolic blood pressure (BP), an index of consistency of BP control, is reportedly associated with major cardiovascular outcomes, the impact of BP-TTR on adverse events in patients with nonvalvular atrial fibrillation (NVAF) has not been thoroughly investigated. Thus, we performed a post hoc analysis to clarify it in patients with NVAF using data of the J-RHYTHM registry. Of 7,406 outpatients with NVAF, 7,226 (age, 70 ± 10 years; men, 71%), in whom BP was measured 4 times or more (15 ± 5 times) during the 2-year follow-up period or until occurrence of an event, constituted the study group. Systolic BP-TTR, with a target range of 110 to 130 mm Hg, was calculated by Rosendaal linear interpolation method. Overall systolic BP-TTR was 50 ± 28%. Thromboembolism, major hemorrhage, all-cause death, and cardiovascular death occurred in 110 (1.5%), 121 (1.7%), 168 (2.3%), and 60 patients (0.8%), respectively. Each 1% increase in systolic BP-TTR was significantly associated with a decreased incidence of all adverse events in the unadjusted model; whereas, significant association was observed only for cardiovascular death (adjusted hazard ratio 0.983, 95% confidence interval 0.971 to 0.995, p = 0.006) after adjusting for known confounders and systolic BP at the time closest to an event. In contrast, each 1% increase in systolic BP time in subtarget range oflt;110 mm Hg was significantly associated with an increased risk of thromboembolism (hazard ratio 1.014, 95% confidence interval 1.005 to 1.024, p = 0.002). In conclusion, systolic BP-TTR and BP time in subtarget range would be useful for risk evaluation of cardiovascular death and thromboembolism, respectively, in patients with NVAF.

Background Heart failure is a worldwide health problem that significantly affects patients’ physical function and health state. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a disease-specific patient-reported outcome measure commonly used for the assessment of health states of patients with heart failure. This study aimed to evaluate the psychometric properties of the Japanese version of the KCCQ. Methods Using pooled data of 141 Japanese patients with chronic heart failure from three clinical trials, the Japanese version of the KCCQ was evaluated for validity and reliability, with a focus on the clinical summary score (CSS) and its component domains. For construct validity, the associations of baseline KCCQ scores with New York Heart Association (NYHA) class and the EuroQol five-dimension, three-level (EQ-5D-3L) scores at baseline were analyzed. For reliability, internal consistency was assessed using Cronbach’s α, and test–retest reliability (reproducibility) was assessed among stable patients. Responsiveness to changes in patients’ clinical status was assessed by analyzing score changes between two timepoints among patients whose health states improved. Results Among 141 patients (mean age, 73.7 ± 10.9 years), 76.6% were NYHA class II at baseline. For CSS and its component domains (physical limitations, symptom frequency, and symptom severity), baseline scores were all significantly lower in patients with a higher NYHA class (p ρ = − 0.40 to − 0.54) with three functional status-related EQ-5D dimensions (mobility, self-care, and usual activities). The Cronbach’s standardized α was high (> 0.70) for all KCCQ domain/summary scores. In the test–retest analysis among 58 stable patients, all domain/summary scores minimally changed by 0.3–4.2 points with intraclass correlation coefficients of 0.65–0.84, demonstrating moderate to good reproducibility, except for the symptom stability domain. Among 44 patients with improved health states, all domain/summary scores except for the symptom stability and self-efficacy domains substantially improved from baseline with a medium to large effect size of 0.62–0.88. Conclusions The Japanese version of the KCCQ was demonstrated to be a valid and reliable tool for the assessment of symptoms and physical function of Japanese patients with chronic heart failure.

Aim: Posterior circulation stroke (PCS) has different clinical features and prognosis compared with anterior circulation stroke (ACS), and whether the effect of statin therapy on stroke prevention differs according to infarction location remains unclear. This post hoc analysis of the J-STARS study aimed to compare the usefulness of statin at different infarction locations (i.e., ACS and PCS). Methods: In the J-STARS study, 1578 patients were randomly assigned to the pravastatin or control group. The subjects were divided into two subgroups (ACS and PCS groups) based on the arteries responsible for the infarction. Cox proportional hazards models were used to investigate whether the all stroke recurrence rate was different between the ACS and PCS groups. Results: The PCS group (n = 499) had a significantly higher prevalence of diabetes than the ACS group (n = 1022) (30.7% vs. 19.8%, P < 0.001). During the follow-up (4.9 ± 1.4 years), the incidence of all stroke was significantly lower in the pravastatin group than in the control group among patients with PCS (adjusted hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25–0.83, P = 0.009); however, the stroke recurrence rates were not significantly different between both groups among patients with ACS (adjusted HR 1.32, 95% CI 0.93–1.88, P = 0.123). A significant interaction between the ACS and PCS groups in terms of pravastatin effects was noted (P = 0.003 for interaction). Conclusions: Pravastatin significantly reduced the recurrence rate of all stroke among patients with PCS. Thus, the effect of statin on the recurrence of stroke may differ according to infarction location.

Aims To understand the different influences of statins on the incidence rate of each stroke subtype in association with low-density lipoprotein (LDL) cholesterol levels, we performed a post hoc analysis on the data from the Japan Statin Treatment Against Recurrent Stroke (J-STARS) study. Methods Subjects (n=1,578) were divided into three groups according to their mean postrandomized LDL cholesterol level (＜100, 100-120, and ≥ 120 mg/dL) until the last observation before the event or the end of follow-up. A Cox proportional hazard model for time to events was used for calculating adjusted hazard ratios, 95% confidence intervals, and the trend tests. Results The event rates for atherothrombotic stroke did not decrease in accordance with the postrandomized LDL cholesterol level subgroups of either the control or the pravastatin group (p=0.15 and 0.33 for the trend, respectively). In the control group, however, no atherothrombotic stroke event was observed in the subgroup of the low postrandomized LDL cholesterol level (less than 100 mg/dL). The event rates for atherothrombotic stroke were lower in the middle postrandomized LDL cholesterol level subgroup (100-120 mg/dL) of the pravastatin group than that of the control group. The event rates for lacunar stroke decreased in the lower postrandomized LDL cholesterol level subgroup of the control group but not of the pravastatin group (p=0.004 and 0.06 for the trend, respectively). Conclusions Statins showed different influences on the risks of atherothromobotic and lacunar stroke according to postrandomized LDL cholesterol levels.

To define the correlation between neuroanatomic and developmental outcomes of children with single ventricle (SV) or transposition of the great arteries (TGA), a prospective longitudinal study was performed in preschool and school-age children. Twenty-seven children with congenital heart disease (9, TGA; 18, SV) were included. Participants underwent 3-dimensional magnetic resonance imaging (MRI) and neurodevelopmental assessment at around 3 years (preschool age) and at 9 years (school age), and 48 healthy controls underwent MRI, and their data were used to derive best-fit models for normal brain volumes for comparisons with congenital heart disease patients. Total brain volume (TBV) and regional brain volumes remained significantly smaller in SV children than in TGA children at both time points, though the growth slope of TBV was not significantly different between the SV and TGA groups. Although the psychomotor developmental index at preschool was significantly lower in SV patients, the full-scale IQ at school age was not significantly lower in SV patients. There was a strong correlation between full-scale IQ and TBV (r = 0.49, P = 0.005). Despite the current best practices, persistently lower TBV was seen in SV patients until 9 years of age. For both the SV and TGA groups, TBV at 3 years was a strong predictor of TBV at 9 years. Since there was a correlation between TBV and IQ at 9 years, identification of factors that affect brain growth until 3 years will be imperative to improve patients' cognitive function at school age.

Background Atrial fibrillation (AF) is a heterogeneous condition caused by various underlying disorders and comorbidities. A cluster analysis is a statistical technique that attempts to group populations by shared traits. Applied to AF, it could be useful in classifying the variables and complex presentations of AF into phenotypes of coherent, more tractable subpopulations. Objectives This study aimed to characterize the clinical phenotypes of AF using a national AF patient registry using a cluster analysis. Methods We used data of an observational cohort that included 7406 patients with non-valvular AF enrolled from 158 sites participating in a nationwide AF registry (J-RHYTHM). The endpoints analyzed were all-cause mortality, thromboembolisms, and major bleeding. Results The optimal number of clusters was found to be 4 based on 40 characteristics. They were those with (1) a younger age and low rate of comorbidities (n = 1876), (2) a high rate of hypertension (n = 4579), (3) high bleeding risk (n = 302), and (4) prior coronary artery disease and other atherosclerotic comorbidities (n = 649). The patients in the younger/low comorbidity cluster demonstrated the lowest risk for all 3 endpoints. The atherosclerotic comorbidity cluster had significantly higher adjusted risks of total mortality (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.37–5.80) and major bleeding (OR, 5.19; 95% CI, 2.58–10.9) than the younger/low comorbidity cluster. Conclusions A cluster analysis identified 4 distinct groups of non-valvular AF patients with different clinical characteristics and outcomes. Awareness of these groupings may lead to a differentiated patient management for AF.

ObjectiveLeft ventricular non-compaction (LVNC) is morphologically characterised by excessive trabeculations and deep recesses in the ventricular wall. The risk of thromboembolic disease in the paediatric patients with LVNC has not been clearly established. We conducted this systematic review to evaluate the prevalence and incidence of thromboembolism (TE) in paediatric and adult patients with LVNC and searched for risk factors for TE to explore management strategies.MethodsThe primary outcome was the prevalence and incidence of TE in the patients with LVNC. The secondary outcome was the TE and mortality and heart transplantation rates between paediatric and adult patients with LVNC. We searched for studies published in MEDLINE, Embase and Cochrane Central Register of Controlled Trials between January 1950 and December 2020. A systematic search of keywords related to LVNC, anticoagulants/antiplatelets and TE was conducted. Studies that did not present original research, non-human studies, duplicated studies were excluded.ResultsFifty-seven studies met the inclusion criteria. A total of 726 paediatric and 3862 adult patients were included. The mean prevalence rates of TE in the paediatric and adult patients with LVNC were 2.6% and 6.2% (I2=0%; p2=73.7%; p2=99.4%; p2=99.5%; pConclusionsThe prevalence and incidence rates in paediatric patients were lower than those in adult patients. TE was associated with a reduced systolic function in paediatric patients with LVNC.

Background: Focusing on medical instruments and materials used for high-risk medicines for cancer treatments, a test on knowledge of medical instruments requiring acquisition of basic knowledge and materials was developed for students in pharmacy school. The aim of the study is to investigate the reliability and validity of the test (medical instruments and materials for cancer treatment-Questionnaire 45; MIMCT-Q45) we developed.Patients and Methods: Focus group discussion was performed by participants consisting of medical staff considered to have abundant experience of cancer chemotherapy. Content analysis was performed and a list of extracted medical instruments and materials was prepared. A questionnaire survey was performed twice in pharmacy students to confirm reliability employing the retest method. Responses were also collected from nurses and pharmacists to investigate discriminative validity on comparison with the students. Furthermore, difficulty and discrimination were estimated using the item response theory (IRT).Results: Thirteen types of medical instruments and materials were extracted and listed in the knowledge test. In the questionnaire survey, the overall Cronbach’s α and interclass correlation coefficient were high, but Cronbach’s α was slightly low (0.56-0.58) in some categories. The range of discrimination estimated based on IRT was 0.98-3.09, and that of difficulty was -0.91-3.00.Conclusions: A knowledge test on cancer chemotherapy-related medical instruments and materials including palliative care at home (MIMCT-Q45) was prepared, and its reliability and validity were confirmed. MIMCT-Q45 might serve as a guidance on basic knowledge to be acquired by students and resident pharmacists and be useful to confirm the level of acquired knowledge.

Background Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke. Methods and Results We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups. Conclusions DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01995370.

Background Machine learning (ML) has emerged as a promising tool for risk stratification. However, few studies have applied ML to risk assessment of patients with atrial fibrillation (AF). Hypothesis We aimed to compare the performance of random forest (RF), logistic regression (LR), and conventional risk schemes in predicting the outcomes of AF. Methods We analyzed data from 7406 nonvalvular AF patients (median age 71 years, female 29.2%) enrolled in a nationwide AF registry (J‐RHYTHM Registry) and who were followed for 2 years. The endpoints were thromboembolisms, major bleeding, and all‐cause mortality. Models were generated from potential predictors using an RF model, stepwise LR model, and the thromboembolism (CHADS2 and CHA2DS2‐VASc) and major bleeding (HAS‐BLED, ORBIT, and ATRIA) scores. Results For thromboembolisms, the C‐statistic of the RF model was significantly higher than that of the LR model (0.66 vs. 0.59, p = .03) or CHA2DS2‐VASc score (0.61, p

Background Data are limited on patient background characteristics associated with catheter ablation (CA)-related bleeding events in Japanese patients with non-valvular atrial fibrillation receiving uninterrupted periprocedural edoxaban. This subanalysis of the KYU-RABLE study focused on univariate and multivariate analyses to identify correlations between bleeding events and baseline patient demographics and CA-related characteristics. Methods Patients with non-valvular atrial fibrillation (NVAF) enrolled from the KYU-RABLE study were included in the study. We performed univariate and multivariate analyses to investigate the correlation of major, minor, and clinically relevant non-major bleeding events with the patient baseline data at enrollment, and with CA procedures. Results A total of 513 NVAF patients were included in the full analysis set. Univariate analysis showed that the incidence of the bleeding events was higher in patients with HAS-BLED score ≥ 3 compared with those with a score p = 0.002), in those with creatinine clearance (CrCL) ≤50 mL/min compared with those with CrCL > 50 mL/min (OR: 10.59, 95% CI: 3.65–30.79; p p = 0.025). Multivariate analysis showed that HAS-BLED score ≥ 3 (OR: 7.93, 95% CI: 1.66–37.88; p = 0.0094) and CrCl ≤ 50 mL/min (OR: 7.78, 95% CI: 2.17–27.90; p = 0.0016) were significant predictors of bleeding events among KYU-RABLE patients. Conclusions These predictors of CA-related bleeding events may allow informed decision-making and better AF patient selection for CA with uninterrupted periprocedural edoxaban. Trial registration KYU-RABLE, UMIN000029693. Registered 1 December 2017.

Background The KYU-RABLE study, a prospective, multicenter, single-arm interventional study, evaluated the efficacy and safety of uninterrupted oral edoxaban in patients undergoing catheter ablation (CA) for atrial fibrillation (AF).Methods and Results:We enrolled patients with AF from 23 centers in Japan. Edoxaban 60 mg (30 mg in patients indicated for dose adjustment) was administered uninterrupted, once daily in the morning for ≥4 weeks before CA and 4 weeks ±7 days after CA with one dose delayed on the procedural day. The primary endpoint was a composite of thromboembolism and major bleeding during 4 weeks from the procedural day. Among the 513 eligible patients who underwent CA, 63.5% received edoxaban 60 mg/day and 36.1% received 30 mg/day. For the primary endpoint, no thromboembolism and 1 major bleeding event (0.2%, cardiac tamponade) were observed. The plasma edoxaban concentration decreased depending on the time from the last administration to the CA procedure. However, plasma levels of coagulative biomarkers were within appropriate ranges regardless of the interval from the last administration of edoxaban. Conclusions The present study provided evidence of the efficacy and safety of uninterrupted edoxaban administered once daily in the morning, with one dose delayed on procedural day, in patients with AF undergoing CA. Edoxaban was associated with a low risk of periprocedural thromboembolic and bleeding complications.

For Japanese patients with non-valvular atrial fibrillation (NVAF), the risk of stroke and major bleeding events was assessed by using the CHADS

BACKGROUND Because the influence of digitalis use on the death of patients with non-valvular atrial fibrillation (NVAF) remains controversial, a subanalysis of the J-RHYTHM Registry was performed.Methods and Results:A consecutive series of outpatients with AF from 158 institutions was enrolled and followed for 2 years or until the occurrence of an event. Among 7,406 patients with NVAF, 7,018 (age, 69.7±10.0 years; men, 71.1%) with information on antiarrhythmic drug and digitalis use at baseline were divided into 2 groups based on digitalis use. The influence of digitalis on death was investigated using a propensity score-matching model. In 802 patients treated with digitalis, all-cause death was significantly higher than in 6,216 patients with no digitalis use during the 2-year follow-up period (4.4% vs. 2.4%, unadjusted P

Background and Purpose— As a prespecified post hoc analysis of the J-STARS (Japan Statin Treatment Against Recurrent Stroke) Echo Study, the 5-year stroke recurrence rate according to the baseline mean carotid intima-media thickness (IMT) with and without pravastatin treatment was investigated. Methods— Patients were randomly assigned to receive pravastatin 10 mg/day (pravastatin group) or control group (nonstatin treatment; 1:1) for 5 years. Baseline mean IMT of the common carotid artery was measured by ultrasonography. Cox proportional hazards models were used to investigate whether the stroke (any ischemic stroke, atherothrombotic brain infarction, or lacunar infarction) recurrence rate was different according to tertiles of baseline mean IMT. Results— A total of 793 patients, including 388 in the pravastatin group and 405 in the control group, were investigated. In the control group, Cox proportional hazards models showed that participants in the highest tertile IMT group (≥0.931 mm) had a higher rate of atherothrombotic brain infarction than those in the lowest tertile IMT group (P value=0.045). Conclusions— Long-term pravastatin administration may prevent the occurrence of atherothrombotic brain infarction in noncardioembolic infarction patients with the highest tertile IMT. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00361530.