Kazunori Toyoda’s research while affiliated with National Cerebral and Cardiovascular Center and other places

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Publications (981)


Efficacy and Safety of intravenous alteplase for unknown onset stroke on prior antiplatelet therapy: post-hoc analysis of the EOS Individual Participant Data
  • Article

February 2025

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19 Reads

International Journal of Stroke

Yuma Shiomi

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Märit Jensen

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Background The effects of intravenous alteplase in patients with prior antiplatelet therapy (APT) remain controversial. We aimed to assess the efficacy and safety of imaging-based intravenous alteplase in patients with unknown-onset stroke with prior APT. Methods Data from randomized controlled trials comparing alteplase with placebo/standard care in patients with unknown-onset acute ischemic stroke from the Evaluation of Unknown Onset Stroke Thrombolysis (EOS) individual patient data meta-analysis collaboration were analyzed. Favorable outcome was defined as a modified Rankin Scale score 0–1 at 90 d poststroke. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 h and 90-d mortality. Results Overall, 780 patients had available baseline data on prior APT. Compared with the no prior APT group (n=523), the prior APT group (n=257) was older (72 years vs. 66 years) and had a higher prevalence of vascular risk factors. There was no interaction between prior APT and treatment effects of alteplase (p for interaction=0.23). In the prior APT patients, 55/125 (45%) patients in the alteplase group and 39/132 (30%) patients in the control group had a favorable outcome (adjusted odds ratio [aOR], 2.07 [95% CI, 1.18–3.64]). The rates of sICH and mortality in the alteplase and control groups were 5.6% and 0.8%, respectively (aOR, 7.78 [0.94–63.37]) and 6.5% and 6.1%, respectively (aOR, 1.12 [0.38–3.36]). In the no prior APT patients, 136 patients (50%) in the alteplase group and 112 patients (45%) in the control group had a favorable outcome (aOR, 1.39 [0.94-2.05]). Safety outcomes were not significantly different between the groups (sICH: 3 [1.1%] vs. 1 [0.4%]; mortality: 13 [4.9%] vs. 3 [1.2%]). Conclusions Alteplase has consistent efficacy regardless of prior APT in patients with unknown-onset stroke. Additionally, prior APT does not significantly increase the risk of sICH or mortality.


Abstract TMP63: Genetic investigation for cerebral small vessel disease genes in patients with spontaneous intracerebral hemorrhage

February 2025

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1 Read

Stroke

Objectives: Spontaneous intracerebral hemorrhage (ICH) is caused by the rupture of small arterioles due to cerebral small vessel disease (SVD), commonly with hypertensive arteriolosclerosis (HTA) or cerebral amyloid angiopathy (CAA). Several genes associated with SVD or ICH have been reported in studies of European populations, but it is unclear whether these genes are associated with ICH in the Japanese cohort. The aim of this study was to assess genetic variants associated with SVD in patients with ICH. Methods: We analyzed 920 patients with primary ICH and genetic data available from an ongoing, prospective, cohort study. ICH was diagnosed according to CLASsification system for ICH (CLAS-ICH) by stroke neurologists, and mixed-SVD was classified as HTA. We focused on the 27 genes previously identified in SVD ( APOE, CETP, PMF1, SLC25A44, TRHDE, APP, NOTCH3, COL4A1, COL4A2, PARVB, FOXC1, FOXF2, TREX1, ZCCHC14, WDR12, ICA1L, GCH1, SH2B3, ACOX1, UNC13D, TRIM65, TRIM47, WBP2, PLEKHG1, EFEMP1, VCAN, HTRA1 ) to investigate their association with the ICH phenotypes (ICH subtypes [HTA-ICH vs. CAA-ICH], hematoma location [non-lobar vs. lobar], modified Rankin Scale (mRS) at 90d [0-4 vs. 5-6]). Variants with minor allele frequency ≥0.05 were analyzed. Trend test was used to assess the association, and the significance level was defined as false discovery rate (FDR) <0.1. The reference allele was defined as a base allele of odds ratio (OR). Results: Characteristics of 920 patients with ICH are mean age 71 ± 13 years, 59% men, HTA-ICH vs. CAA-ICH:88% vs. 10%, non-lobar vs. lobar: 74% vs. 26%, and mRS 0-4 vs. 5-6: 78% vs. 22%. We assessed the 667 variants in 27 genes. In CAA-ICH vs HTA-ICH, two variants on APP (amyloid-β protein precursor) gene showed significance. One was rs2830008 (NM_000484:c.865+2696A>G, OR=2.67, p=5.9×10 ⁻⁶ , FDR=0.039) and the other was rs73163761 (NM_000484:c.866-7085C>T, OR=2.59, p=1.9×10 ⁻⁴ , FDR=0.064). These 2 variants were in linkage equilibrium (r ² =0.93). The alternative allele frequencies of rs2830008: T>C and rs73163761: G>A were 0.182 vs. 0.077 and 0.166 vs. 0.071 in CAA-ICH vs. HTA-ICH, respectively, with the HTA-ICH frequencies aligning with those of the general population (0.081, 0.072, respectively). No significant association was observed for other phenotypes. Conclusion: We found that 2 variants on APP genes were associated with CAA-ICH in the Japanese ICH cohort, confirming the link to amyloid β pathology.


Abstract TMP73: Endovascular therapy for acute ischemic stroke beyond 24 hours after onset: Japan Stroke Data Bank

February 2025

Stroke

Background: The therapeutic time window of endovascular therapy (EVT) for acute ischemic stroke (AIS) has been expanded up to 24 hours of onset. Patients with AIS beyond 24 hours may also benefit from EVT, but the actual status of this clinical issue is unknown. Purpose: To evaluate the real-world status of EVT for AIS beyond 24 hours of onset using a nation-wide stroke registry, Japan Stroke Data Bank (JSDB). JSDB is an ongoing hospital-based multicenter prospective registry of hospitalized patients with acute stroke or transient ischemic attack within 7 days of onset. Methods: From the JSDB dataset, patients with AIS who underwent EVT from 1996 through 2021 were analyzed. Patients were divided into 3 groups according to time from onset to hospital arrival (early: <4.5 hour; late: 4.5–24 hour; and very late: >24 hour). Outcomes included the favorable outcome (mRS 0–2 or return to pre-stroke mRS at discharge) and in-hospital mortality. Results: Among the 256,293 stroke patients, 91,907 AIS patients available for analysis were included in the present study. EVT was implemented in 6.9% (6,356/91,907) (median age 78 years; 41.6% women; median NIHSS score 16). The EVT rate by time window groups was 11.8% (4,258/36,044) for the early, 5.3% (1,676/31,328) for the late, and 1.7% (422/24,535) for the very late group. In the very late group with EVT, baseline NIHSS score was lowest (median 17 points in the early group, 14 points in the late group, and 5 points in the very late group), cardioembolism was least common (67.2%, 53.5%, and 22.0%, respectively), and large artery atherosclerosis was most common (17.9%, 30.8%, and 55.7%, respectively). Favorable outcome was more frequently achieved in the very late group (52.9%) than in the early (41.6%) and late (36.5%) groups. Symptomatic intracranial hemorrhage was more frequently seen in the very late group (6.0%) compared to the early (2.9%) and late (3.8%) groups, but in-hospital mortality was comparable among the time window groups (8.1% in the early group, 7.1% in the late group, and 6.6% in the very late group). Conclusions: Outcomes after EVT for patients with AIS beyond 24 hours were not necessarily worse than for patients with AIS up to 24 hours, but the patient profile in the very late group with EVT differed significantly from that in the early and late groups; developing optimal patient selection strategies for very late AIS may be required.


Abstract WMP29: Evaluating Exemption from Informed Consent and Deferred Consent Practices in Acute Stroke Trials: A Scoping Review of Recent Trends and Recruitment Efficiency.

February 2025

Stroke

Purpose: Recruiting participants for acute ischemic stroke trials is challenging due to difficulties in obtaining written informed consent in urgent settings. Alternative consent methods, like deferred consent and Exemption from Informed Consent (EFIC), have been proposed to facilitate timely intervention and improve trial feasibility. This review examines the impact of these methods on recruitment efficiency in both ischemic stroke and ICH trials. Methods: A scoping review of trials on acute ischemic stroke and ICH interventions (enrollment ≤24 hours from onset) published between January 2013 and March 2023 was conducted. Studies were categorized by consent methods, and trial characteristics were analyzed to compare recruitment efficiency. The review protocol was pre-registered on the Open Science Framework (https://osf.io/5rkc2). Results: A total of 170 trials met our inclusion criteria. Of these, 118 trials used conventional written informed consent (Conventional group), while 52 trials (30.6%) adopted alternative consent methods including deferred consent and EFIC (Alternative group). In univariable analysis, the Alternative group had a significantly shorter maximum allowable time from onset/LKW to randomization/enrollment compared to the Conventional group (6 hours [IQR 4-12] vs. 9 hours [IQR 5-24], p=0.03). There were no significant differences between the groups in terms of the number of participating countries, sites, or overall enrollment duration. However, the number of withdrawals (in counts) was significantly higher in the Alternative group (2.8 ± 5.8 vs. 9.3 ± 13, p<0.001). Additionally, alternative consent strategies were more frequently used in pre-hospital settings, where patients were often enrolled before a clinical diagnosis was confirmed. In the multivariable regression analysis, adjusting for operational factors (number of participating countries, sites, patients) and trial design elements (blinding, randomization, intervention), the Alternative group showed no significant difference in enrollment duration compared to the Conventional group (β = -0.32 weeks, 95% CI: -8.1 to 7.4, p = 0.93). Conclusions: Alternative consent methods, used in approximately 30% of acute stroke trials, allow quicker enrollment without significantly impacting overall enrollment duration. However, these methods are linked to higher dropout rates. These strategies require careful implementation to balance speed and trial feasibility.


Abstract 118: Long Term Outcomes in the CHARM Trial Evaluating Intravenous Glyburide for the Treatment of Large Hemispheric Infarction

February 2025

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1 Read

Stroke

Introduction: The phase III CHARM trial evaluated the safety and efficacy of intravenous glyburide as a treatment for large hemispheric infarction (LHI) patients at high risk for cerebral edema. Hypothesis: We aimed to determine whether subjects who were treated with IV glyburide would have better 12-month outcomes than those who received placebo in the CHARM trial. Methods: The source population included all CHARM subjects who were enrolled and treated with IV glyburide or placebo and had a recorded 12-month outcome. For those subjects missing a 12-month outcome, multiple imputation including baseline covariates and the 90-day modified Rankin Scale (mRS) was used. Shift analysis was performed on the 12-month mRS using 5 categories, where 0-1 and 5-6 were each collapsed into a single category. Independent variables included age, sex, baseline NIHSS, world region, tPA, and thrombectomy. Based on prior analysis, we also examined subjects with a baseline stroke volume ≤125 mL. Results: The cohort included a total of 431 subjects (mean age 58±9 years, 33% female, baseline NIHSS 19 (16-22), 40% received thrombolysis), the median 90-day mRS was 5 (4-6) and the median 12-month mRS was 5 (3-6). A total of 90 subjects (21%) had missing 12-month outcomes (n=38 in glyburide and n=52 in placebo). The correlation between 90d and 12mo mRS was r=0.93, p<0.0001. At 12 months, IV glyburide was not associated with better functional outcome (cOR 1.09, 95% CI 0.73-1.62, p=0.68) in the primary analytic population. However, among the subgroup of subjects with a baseline stroke volume ≤125 mL (n=118), the IV glyburide treatment arm had a favorable effect, cOR 2.26, 95% CI 1.06-4.78, p=0.034 (see figure). This effect was also present among those treated with endovascular thrombectomy at baseline (n=34, cOR 5.52, 95% CI 1.05-28.9, p=0.043). Conclusions: Long term outcomes in the CHARM trial suggests a potential for durable improvement in functional outcome in patients treated with IV glyburide among those with a baseline stroke volume ≤125 mL. Demonstration of clinical efficacy requires a dedicated trial focusing on this patient population.


Abstract 56: Intravenous Glyburide in Large Core, Endovascular-Treated Stroke Patients: An Analysis of the CHARM Trial

February 2025

Stroke

Introduction: Recent large core stroke trials show a benefit for endovascular treatment (EVT) of acute ischemic stroke up to approximately 125 mL. Consequently, clinical trials evaluating neuroprotection in EVT populations may best test proof of concept under this volume threshold. The CHARM trial evaluated the safety and efficacy of intravenous glyburide as a treatment for large hemispheric infarction (LHI) patients at high risk for cerebral edema. Hypothesis: The objective of this analysis was to examine the treatment effect of IV glyburide in EVT patients with baseline infarcts up to 125 mL. Methods: CHARM subjects who were enrolled with CTP or DWI volume 80-125 mL and underwent EVT were included in this analysis. The primary endpoint was a shift analysis on the 90-day modified Rankin Scale (mRS) and included participants aged ≤70 years who received any study drug. Independent variables included age, sex, baseline NIHSS, world region, and tPA. We also examined the frequency of decompressive craniectomy and the amount of midline shift (mm) by treatment group. Results: For a total of 34 subjects (mean age 56 years, 32% female, baseline NIHSS 20, 41% received thrombolysis), the time to thrombectomy was 4.5±2.0 hours and time to study drug was 9.6±1.4 hours. glyburide-treated patients received study drug later than placebo by an average of 1 hour ( P =0.036). The baseline infarct volume was 94±20 mL, which did not differ by treatment arm. glyburide-treated subjects had a favorable outcome (n=18, cOR 7.13, 95%CI 1.51-33.7, P =0.013) relative to placebo (see figure). 90-day mortality occurred less frequently in glyburide treated subjects compared to placebo (5.6% vs 31%, P =0.05). There were no decompressive craniectomies in glyburide treated patients, whereas there were 4 decompressions among the placebo-treated subjects ( P =0.021). The mean midline shift was 4.2 ± 2.5 mm in IV glyburide-treated subjects and 7.6 ± 5.5 mm among placebo-treated subjects ( P =0.024). Conclusions: There is evidence of benefit for IV glyburide in large core EVT treated subjects with a baseline stroke volume ≤125 mL. Although IV glyburide may also have benefit among non-EVT treated subjects, the evolving standard of care of EVT for large core stroke indicates that an efficient, feasible trial design should focus on EVT patients.


Abstract WMP26: Clinical Characteristic-Driven Machine Learning Models for the Prediction of Stroke Subtypes and Eligibility of Endovascular Thrombectomy

February 2025

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5 Reads

Stroke

Introduction: Several pre-hospital scales predict ischemic stroke due to large vessel occlusion; however, these scales often fail to detect atypical endovascular thrombectomy (EVT) cases, including posterior circulation and distal vessel occlusion. Additionally, these pre-hospital scales cannot differentiate between stroke subtypes, such as ischemic stroke and intracerebral hemorrhage. We aimed to develop machine learning (ML) models to predict stroke subtypes and EVT eligibility. Methods: We conducted an analysis using data from the Japan Stroke Data Bank, a nationwide acute stroke registry. Patients with ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage who were hospitalized between 2016 and 2020 were included in this study. We developed two ML models: (1) a model to predict patients who received EVT, and (2) to predict stroke categories (ischemic stroke treated with EVT, ischemic stroke treated with tPA, ischemic stroke without EVT or tPA, intracerebral hemorrhage, and subarachnoid hemorrhage). Patient data were divided into the derivation cohort (data from 2016 to 2019) and the validation cohort (data in 2020). The input variables for the ML models consisted of 129 clinical characteristics, including past medical history and neurological examination findings. Imaging and laboratory data were not utilized in the ML process. We initially developed the ML models using LightGBM algorithm with all 129 variables. Subsequently, we selected the top 10 variables for model development by the feature importance and Brute-force method, comparing commonly used pre-hospital scales to predict patients with EVT. Results: Of the 62,588 patients included in the study, 4,353 were treated with EVT, 3,001 with tPA, 39,710 had ischemic stroke treated without EVT or tPA, 12,498 had intracerebral hemorrhage, and 3,028 had subarachnoid hemorrhage. The area under the curve (AUC) for predicting patients treated with EVT was 0.828 (95% CI 0.817-0.839). For predicting the five stroke categories, the multiclass AUC was 0.848, and the micro-average F1 score was 0.705. Using the brute-force algorithm to select 10 variables, the ML model for predicting EVT treatment achieved an AUC of 0.794 (95% CI 0.784-0.805), outperforming commonly used pre-hospital scales (AUC 0.584-0.690). Conclusions: The ML models utilizing only clinical characteristics can accurately predict stroke subtypes and EVT eligibility, offering a potential improvement over current pre-hospital scales.


Abstract WMP102: Ischemic and hemorrhagic risks of patients with cortical superficial siderosis on antithrombotic therapy

February 2025

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2 Reads

Stroke

Objectives: Cortical superficial siderosis (cSS) has been implicated as a putative hemorrhagic MRI finding of cerebral small vessel disease (SVD) related to cerebral amyloid angiopathy. Few reports have examined the association between cSS and antithrombotic-related clinical events. The aim of this study is to investigate the association of cSS with the risk of hemorrhagic or ischemic events in patients receiving antithrombotic agents. Methods: This is a prospective, multicenter, observational study that enrolled patients with cerebrovascular or cardiovascular diseases who were taking oral antithrombotic agents from 52 hospitals across Japan between 2016 and 2019. The MRI scans were centrally evaluated for SVD, including white matter hyperintensities (WMH), cerebral microbleeds (CMBs), lacunes, basal ganglia-enlarged perivascular spaces (BGPVS), cortical superficial siderosis (cSS), using a visual scale. The outcomes included subsequent ischemic events (ischemic vascular events [IVE], ischemic stroke [IS]), hemorrhagic events (major bleeding [MB], intracranial hemorrhage [ICH], non-major bleeding[nMB]), and mortality. We calculated incidence rates (IR) per 1,000 patient-years of each event and the IR ratio (IRR). Results: Of 5037 patients (mean age 71.2 ± 11.2 years, 67% men), cSS was detected in 105 (2.0%) patients. The cSS group was older and had a higher proportion of males, atrial fibrillation, histories of intracerebral hemorrhage or subarachnoid hemorrhage and a higher frequency of strictly lobar CMBs, WMH, and lacunes compared to the non-cSS group. During a median 2 [IQR1.8–2.03] years, 278 IVE, 197 IS, 93 MB, 55 ICH, 147 nMB, and 217 deaths were observed. In the cSS group, IVE and IS were numerically less frequent (IVE: IR 20.95 vs 29.13; IS: 15.64 vs 20.34, per 1000 patient-years), while MB and mortality (MB: IR 9.61 vs 5.15; mortality: IR 35.82 vs 21.87) were numerically more frequent, compared to the non-cSS group, but the IRR of each event did not significantly differ between the 2 groups. In the cSS group on warfarin (n=12), there was a trend towards numerically higher rates of MB (IR 80.36 vs 18.54), ICH (IR 80.36 vs 15.84), and mortality (IR 142.95 vs 39.61, per 1000 patient-years) compared to the non-cSS group. Conclusion: Individuals with cSS receiving antithrombotic agents exhibited a higher trend for mortality and major bleeding.


Abstract WP4: Imaging-based Intravenous Thrombolysis for Patients ≥85 Years with Unknown Onset Stroke: EOS Individual Patient Data Meta-Analysis

February 2025

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3 Reads

Stroke

Introduction: Previous studies have shown the efficacy and safety of time-based intravenous thrombolysis (IVT) in elderly patients with ischemic stroke. However, there are safety concerns about bleeding associated with IVT due to their low body weight, renal dysfunction, and the concomitant use of antithrombotic drugs. Robust evidence on the effect of IVT, particularly in elderly patients with unknown onset stroke, is limited. This study aimed to evaluate the efficacy and safety of imaging-based IVT in this population. Methods: Patients with an unknown onset stroke were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo or standard treatment from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration. The primary outcome was favorable outcome, defined as a mRS score of 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22–36 hours and 90-day mortality. The effect of IVT was evaluated in each of patients aged ≥85 and <85 years using a mixed-effect logistic regression analysis. Results: Among the 843 patients in the EOS dataset, 56 were aged 85 years or older (6.7%), and 787 were under 85 years (93.3%). The elderly group had a higher prevalence of atrial fibrillation (42.9% vs. 17.2%), hypertension (78.6% vs. 58.7%), and premorbid anticoagulation (13.6% vs. 3.1%). The baseline NIHSS score was also higher (median, 12 vs. 7) (all p<0.05). Overall, there was no significant interaction between age (≥85 or <85 years) and treatment on efficacy or safety outcomes (P interaction for the primary outcome 0.689). In the elderly group, favorable outcomes were observed in 33.3% of the IVT group and 19.2% of the control group, with an adjusted odds ratio (aOR) of 3.06 (95% CI 0.68-13.8). Mortality at 90 days was not significantly different between the IVT and control groups (20.0% vs. 19.2%, aOR 1.32 [0.30-5.79]), and there was only one case of sICH in the IVT group. In patients under 85 years, favorable outcomes were observed in 48.5% of the IVT group compared to 40.5% in controls (aOR 1.50, 95% CI 1.09-2.06). The IVT group had higher mortality (5.8% vs. 2.3%, aOR 2.56, [1.16-5.67]) and more frequent sICH (2.7% vs. 0.5%, aOR 5.35, [1.18-24.3]). Conclusion: Imaging-based IVT with alteplase may improve outcomes in elderly patients with unknown onset stroke without significantly increasing the risk of death or sICH.


Abstract 5: Glyburide for Large Hemispheric Infarcts ≤125 mL: a Meta-Analysis of Individual Patient Data from the GAMES-RP and CHARM Trials

February 2025

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2 Reads

Stroke

Introduction: Two randomized trials have evaluated intravenous (IV) Glyburide for the treatment of large hemispheric infarction (LHI) patients at high risk for cerebral edema. Hypothesis: In this meta-analysis of two randomized trials, we aimed to determine whether subjects with a baseline stroke volume ≤125 mL who were treated with IV Glyburide would have better outcomes than those who received placebo. Methods: The source population included all GAMES-RP and CHARM subjects who were enrolled and treated with IV Glyburide or placebo, were ≤70 years of age, and had a baseline stroke volume ≤125 mL (n=138). The outcome of interest was the modified Rankin Scale (mRS) score at 90 days using 5 categories, where 0-1 and 5-6 were each collapsed into a single category. We used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in the subgroup with a baseline stroke volume ≤125 mL after adjustment for age, sex, baseline NIHSS, region of world, image modality, thrombolysis and thrombectomy (yes versus no). Results: The cohort included a total of 138 subjects with a mean age 58±10 years, 34% female, baseline NIHSS 18 (15-21), 46% received thrombolysis, baseline stroke volume 97 ml (84-108). The median 90-day mRS was 3 (2-4). Among these patients at 90 days, IV Glyburide was associated with better functional outcome (cOR 2.56, 95% CI 1.28-5.11, p=0.008). Conclusions: Individual patient data meta-analysis of 138 subjects enrolled in the GAMES-RP and CHARM trials show that IV Glyburide was associated with an improvement in functional outcome compared to placebo when the baseline stroke volume was ≤125 mL. This finding requires confirmation in a future clinical trial.


Citations (39)


... A potential novel option for patients with breakthrough stroke is LAA occlusion as a matched observational cohort study found a lower risk of recurrent stroke compared to standard-of-care DOAC therapy alone in patients with breakthrough stroke (HR: 0.33, 95% CI: 0.19-0.58). 72 Although promising, a major limitation of these data is that for the LAA occlusion patients, follow-up started from the moment of the LAA occlusion procedure bypassing the high-risk early post stroke time period, while for the non-LAA occlusion cohort, follow-up started immediately after the index event (inclusive of the high-risk early post stroke time period) introducing substantial bias in favor of LAA occlusion. As such, uncertainty remains and this approach is currently being investigated in RCTs (NCT05976685; NCT05963698). ...

Reference:

Ischemic Stroke Prevention in Patients Atrial Fibrillation and a Recent Ischemic Stroke, TIA, or Intracranial Hemorrhage; a World Stroke Organisation (WSO) Scientific Statement
Left Atrial Appendage Occlusion vs Standard of Care After Ischemic Stroke Despite Anticoagulation
  • Citing Article
  • September 2024

JAMA Neurology

... 5 The All Nippon AF In Elderly (ANAFIE) Registry, a prospective multicenter observational study in Japan, provided real-world insights into NVAF in >30,000 elderly (age ≥75 years) Japanese patients. 6 Over a 2-year follow-up period, NOACs yielded a numerically lower event incidence vs. warfarin in all age groups and for majority of endpoints, except major bleeding in patients aged ≥90 years. 6 Although NOACs, compared with warfarin, offered potential benefits for stroke prevention, they had limited efficacy in reducing major bleeding among those aged ≥90 years, indicating a potential benefit of very-low-dose NOACs for this demographic. ...

Patient Outcomes in Very Elderly Patients With Non-Valvular Atrial Fibrillation ― ANAFIE Registry ―
  • Citing Article
  • Full-text available
  • July 2024

Circulation Reports

... In diabetes management, cilostazol may enhance the peripheral circulation and insulin sensitivity, potentially augmenting the hypoglycemic effects of drugs like insulin or sulfonylureas, thereby increasing the risk of hypoglycemia [52,53]. Conversely, it may counteract the hyperglycemic side effects of thiazide diuretics or beta-blockers [54,55]. In hypertension, its vasodilatory properties can synergize with anti-hypertensive medications, such as calcium channel blockers or ACE inhibitors, potentially leading to excessive reductions in blood pressure and postural hypotension. ...

Blood pressure during long-term cilostazol-based dual antiplatelet therapy after stroke: a post hoc analysis of the CSPS.com trial

Hypertension Research

... All patients with AIS due to large vessel occlusion (LVO) caused by intracranial atherosclerosis or extracranial carotid atherosclerosis admitted within 7 days of the last known well (LKW) were retrospectively registered in the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolic and Atherothrombotic Stroke with Large Vessel Occlusion (RESCUE AT-LVO) (18,19), a historical multicenter registry that included data from 51 hospitals in Japan from January 2017 to December 2019. ...

Optimal Endovascular Therapy Technique for Isolated Intracranial Atherothrombotic Stroke-Related Large-Vessel Occlusion in the Acute-to-Subacute Stage
  • Citing Article
  • July 2024

American Journal of Neuroradiology

... Comparándola con la alteplasa tenemos cifras que se encuentran entre 26% hasta 56%. En estudio del placebo nos da un valor de 29% (25,26,27,29,30,31,32,39). ...

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke
  • Citing Article
  • May 2024

Stroke

... The incidence of bleeding events was approximately 6.77 events per 100 person-years. This result exceeds the gastrointestinal (GI) bleeding rate reported in the elderly subgroup analysis of the All-Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry, which documented 1.92 events per 100 person-years (Yamamoto et al., 2024). Conversely, it is lower than findings from the WATER registry in Turkey, where major bleeding was observed in 29 patients (5.1%) and minor bleeding in 222 patients (38.8%) (Turk et al., 2015). ...

Gastrointestinal bleeding in elderly patients with atrial fibrillation: prespecified All Nippon Atrial Fibrillation in the Elderly (ANAFIE) Registry subgroup analysis

... Stroke remains a major health problem worldwide. The burden of stroke is especially high in Asia which is home to more than 60% of the world's population, contributes an estimated 10 million strokes annually to the global stroke caseload, and accounts for a large proportion of strokerelated death and disability worldwide [1,2]. While the majority of strokes are related to the well-known cardiovascular risk factors, many unique and fascinating causes of stroke, rarely encountered in the Western world, are seen in Asia, especially in the tropical South and Southeast Asian regions. ...

Stroke in Asia

Cerebrovascular Diseases Extra

... An inverse J-shaped relationship was also found between BMI of 23.07 kg/m 2 and the lowest risk of all-cause mortality in stroke patients (49). It's noteworthy that high mortality risks associated with being underweight (BMI <18.5 kg/m 2 ) in patients with cardiovascular and cerebrovascular diseases have been consistently observed in multiple studies (47)(48)(49)(50). Based on this evidence, BMI may play a significant role in the L-shaped relationship between ABI and the all-cause and cardiovascular mortality among MACCE survivors. ...

Clinical impact of body mass index on ischemic and hemorrhagic stroke

International Journal of Stroke

... Noteworthy, high frequency of p.Arg544Cys variants in asian populations (China, Korea and Taiwan) could be the underlying reason of this difference [34,37] which shows the impact of different variants on the radiological symptoms. Also, in a recent study including Japanese and Korean cohorts showed an Arg75Pro mutation to have a 24% frequency and without the temporolobal lesions [38]. Finally, this could be interpreted in the context of difference in the underlying gain-of-function versus loss-of-function effects of missense and null variants in the NOTCH3 gene. ...

Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property

Annals of Neurology

... However, only about 5-25% of patients are eligible for this treatment due to the narrow therapeutic window. 1 One reason for exclusion is patients with an unknown onset of symptoms, which occurs in cases of wake-up or unwitnessed stroke where the symptom onset time cannot be estimated due to aphasia, impaired consciousness, or cognitive impairment. 2 Several clinical trials have been conducted to extend the treatment window for patients with the potential to salvage penumbral brain tissue using imaging-based selection, in addition to clinical criteria. For instance, the WAKE-UP trial showed a significantly better functional outcome in patients with an unknown time of onset who were treated with intravenous alteplase (ALT) and MRI guidance. ...

Thrombolysis for Wake-Up Stroke Versus Non-Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis
  • Citing Article
  • March 2024

Stroke