Endovascular Therapy for Acute Stroke with a Large Ischemic Region.

BACKGROUND: Endovascular therapy for acute ischemic stroke is generally avoided when the infarction is large, but the effect of endovascular therapy with medical care as compared with medical care alone for large strokes has not been well studied. METHODS: We conducted a multicenter, open-label, randomized clinical trial in Japan involving patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) value of 3 to 5 (on a scale from 0 to 10, with lower values indicating larger infarction). Patients were randomly assigned in a 1:1 ratio to receive endovascular therapy with medical care or medical care alone within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images. Alteplase (0.6 mg per kilogram of body weight) was used when appropriate in both groups. The primary outcome was a modified Rankin scale score of 0 to 3 (on a scale from 0 to 6, with higher scores indicating greater disability) at 90 days. Secondary outcomes included a shift across the range of modified Rankin scale scores toward a better outcome at 90 days and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours. RESULTS: A total of 203 patients underwent randomization; 101 patients were assigned to the endovascular-therapy group and 102 to the medical-care group. Approximately 27% of patients in each group received alteplase. The percentage of patients with a modified Rankin scale score of 0 to 3 at 90 days was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval [CI], 1.35 to 4.37; P = 0.002). The ordinal shift across the range of modified Rankin scale scores generally favored endovascular therapy. An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (relative risk, 3.51; 95% CI, 1.76 to 7.00), and any intracranial hemorrhage occurred in 58.0% and 31.4%, respectively (P<0.001). CONCLUSIONS: In a trial conducted in Japan, patients with large cerebral infarctions had better functional outcomes with endovascular therapy than with medical care alone but had more intracranial hemorrhages. (Funded by Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy; RESCUE-Japan LIMIT ClinicalTrials.gov number, NCT03702413.).

Expanding the Treatable Imaging Profile in Patients With Large Ischemic Stroke: Subanalysis From a Randomized Clinical Trial.

BACKGROUND: We aimed to examine the boundary of the ischemic core volume in patients undergoing endovascular thrombectomy (EVT) versus those receiving medical management to determine the minimum optimal size for favorable treatment outcomes. METHODS: This is a prespecified substudy of the RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism-Japan Large Ischemic Core Trial). Patients with large vessel occlusion were enrolled between November 2018 and September 2021 with a National Institutes of Health Stroke Scale score of at least 6 on admission and an Alberta Stroke Program Early Computed Tomography Score value of 3 to 5. We investigated the correlation between optimal quantified ischemic core volume, assessed solely using magnetic resonance diffusion-weighted imaging, and functional outcomes (modified Rankin Scale score, 0-3) at 90 days by predictive marginal plots. Final infarct volume and safety outcomes (symptomatic intracerebral hemorrhage and mortality) were also assessed. RESULTS: Of the 203 cases, 168 patients (85 in the EVT group versus 83 in the medical management group) were included. The median (interquartile range) core volume was 94 (65-160) mL in patients with EVT and 115 (71-141) mL in the medical management group (P=0.72). The predictive marginal probabilities of the 2 groups intersected at 128 mL for estimating functional outcomes. Symptomatic intracerebral hemorrhage and mortality within 90 days had overlay margins through all core volumes in both groups. The median final infarct volume (interquartile range) was smaller in the EVT group (142 [80-223] mL versus 211 [123-289] mL in the medical management group; P<0.001). CONCLUSIONS: In this prespecified analysis of a randomized clinical trial involving patients with large ischemic strokes, patients with an estimated core volume of up to 128 mL on diffusion-weighted imaging benefit from EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03702413.

Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Outcomes of Bridging Intravenous Thrombolysis Versus Endovascular Therapy Alone in Late-Window Acute Ischemic Stroke.

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

One-year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after acute large vessel occlusion stroke.

Although low-dose direct oral anticoagulants (DOACs) are recommended for patients at high risk of bleeding complications, it remains unclear whether the dose reduction in real-world setting is also appropriate in patients after large-vessel occlusion (LVO) stroke. This study hypothesized that patients with atrial fibrillation (AF) and LVO receiving low-dose DOACs have an increased risk of ischemic and hemorrhagic events. The study aimed to assess 1 year morbidity and mortality in patients treated with standard-dose and low-dose apixaban after LVO stroke. A post hoc analysis was performed using the acute LVO registry data, which enrolled patients with AF and LVO who received apixaban within 14 days of stroke onset. The incidences of ischemic events (ischemic stroke, acute coronary syndrome, acute myocardial infarction, and systemic embolism), major bleeding events, and death from any cause were compared between patients receiving standard- and low-dose apixaban. Of 643 patients diagnosed with LVO, 307 (47.7%) received low-dose apixaban. After adjustment for clinically relevant variables, no significant differences were observed in the incidence of ischemic events (adjusted hazard ratio [aHR]: 2.12, 95% confidence interval [CI] 0.75-6.02), major bleeding events (aHR: 1.17, 95% CI 0.50-2.73), and death from any cause (aHR: 1.95, 95% CI 0.78-4.89) between patients receiving standard- and low-dose apixaban. No significant differences were observed in the incidence of ischemic events, major bleeding events, or death from any cause between patients with AF and LVO receiving standard- and low-dose apixaban.

Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT.

BACKGROUND: The increased risk of intracranial hemorrhage with multiple passes in endovascular therapy (EVT) for large vessel occlusion with a large ischemic core is a concern. We explored the effect of the number of EVT passes on patients in a randomized clinical trial. METHODS: This post hoc study was the secondary analysis of RESCUE-Japan LIMIT, which was a randomized clinical trial comparing EVT and medical treatment alone for large vessel occlusion with large ischemic core. We grouped patients according to the number of passes with successful reperfusion (modified Thrombolysis in Cerebral Infarction score, ≥2b) in 1, 2, and 3 to 7 passes and failed reperfusion (modified Thrombolysis in Cerebral Infarction score, 0-2a) after any pass in the EVT group, and these groups were compared with medical treatment group. The primary outcome was modified Rankin Scale score of 0 to 3 at 90 days. Secondary outcomes were improvement in National Institutes of Health Stroke Scale score of ≥8 at 48 hours, mortality at 90 days, symptomatic intracranial hemorrhage, and any intracranial hemorrhage within 48 hours. RESULTS: The number of patients who received EVT with successful reperfusion after 1, 2, and 3 to 7 passes and failed reperfusion were 44, 23, 19, and 14, respectively, and 102 received medical treatment alone. The adjusted odds ratios (95% CIs) for the primary outcome relative to medical treatment were 5.52 (2.23-14.28) after 1 pass, 6.45 (2.22-19.30) after 2 passes, 1.03 (0.15-4.48) after 3 to 7 passes, and 1.17 (0.16-5.37) if reperfusion failed. The adjusted odds ratios (95% CIs) for any intracranial hemorrhage within 48 hours relative to medical treatment were 1.88 (0.90-3.93) after 1 pass, 5.14 (1.97-14.72) after 2 passes, 3.00 (1.09-8.58) after 3 to 7 passes, and 6.16 (1.87-24.27) if reperfusion failed. CONCLUSIONS: The successful reperfusion within 2 passes was associated with better clinical outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03702413.

Cost-effectiveness of Endovascular Treatment for Acute Stroke with Large Infarct: A United States Perspective.

Background The health economic benefit of endovascular treatment (EVT) in addition to best medical management for acute ischemic stroke with large ischemic core is uncertain. Purpose To assess the cost-effectiveness of EVT plus best medical management versus best medical management alone in treating acute ischemic stroke with large vessel occlusion and a baseline Alberta Stroke Program Early CT Score (ASPECTS) 3-5. Materials and Methods This is a secondary analysis of the randomized RESCUE-Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism-Japan Large Ischemic Core Trial), with enrollment November 2018 to September 2021, in which the primary outcome was the modified Rankin Scale (mRS) score at 90 days. Participants with a baseline ASPECTS 3-5 (on the basis of noncontrast CT and diffusion-weighted imaging) were randomized 1:1 to receive EVT plus best medical management (n = 100) or best medical management alone (n = 102). The primary outcome of the current study was cost-effectiveness, determined according to the incremental cost-effectiveness ratio (ICER). A decision model consisting of a short-term component (cycle length of 3 months) and a long-term Markov state transition component (cycle length of 1 year) was used to estimate expected lifetime costs and quality-adjusted life-years (QALYs) from health care and societal perspectives in the United States. Upper and lower willingness-to-pay (WTP) thresholds were set at $100 000 and $50 000 per QALY, respectively. A deterministic one-way sensitivity analysis to determine the impact of participant age and a probabilistic sensitivity analysis to assess the impact of parameter uncertainty were conducted. Results A total of 202 participants were included in the study (mean age, 76 years ± 10 [SD]; 112 male). EVT plus best medical management resulted in ICERs of $15 743 (health care perspective) and $19 492 (societal perspective). At the lower and upper WTP thresholds, EVT was cost-effective up to 85 and 90 years (health care perspective) and 84 and 89 years (societal perspective) of age, respectively. When analyzing participants with the largest infarcts (ASPECTS 3) separately, EVT was not cost-effective (ICER, $337 072 [health care perspective] and $383 628 [societal perspective]). Conclusion EVT was cost-effective for participants with an ASPECTS 4-5, but not for those with an ASPECTS 3. ClinicalTrials.gov registration no. NCT03702413 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Widjaja in this issue.

Safety of Apixaban Monotherapy for Non-Valvular Atrial Fibrillation-Related Acute Stroke with Intra-/Extracranial Artery Stenosis.

INTRODUCTION: We investigated whether apixaban is safe for the prevention of further adverse events in non-valvular atrial fibrillation (NVAF) patients with intra-/extracranial artery stenosis (Stenosis group) compared with acute large vessel occlusion without intra-/extracranial artery stenosis (No stenosis group). We also examined whether combination therapy using apixaban and antiplatelet is safe. METHODS: ALVO (Apixaban on clinical outcome of patients with Large Vessel Occlusion [LVO] or stenosis) was a historical and prospective multicenter registry at 38 centers in Japan. Patients with NVAF and acute LVO or stenosis who received apixaban within 14 days after onset were included. We conducted the post hoc analysis using the ALVO dataset. We compared patients with stenosis versus those without stenosis in terms of the primary outcome, which was defined as a composite of all-cause death, major bleeding events, and ischemic events 365 days after onset. RESULTS: Of the 662 patients, 54 (8.2%) patients were classified into the Stenosis group, and 104 patients of the total (16%) reached the primary outcome. The cumulative incidence of primary outcome was not significantly different between the No stenosis and the Stenosis groups (hazard ratio [HR] 1.2, 95% confidence interval [CI]: 0.64-2.4; p = 0.52). Even after adjustment for predictive clinical variates, no significant difference in the primary endpoint between the No stenosis and the Stenosis groups was shown (adjusted HR 1.2, 95% CI: 0.59-2.5; p = 0.60). Fifty patients (7.6%) used an antiplatelet with apixaban. Among the Stenosis group patients, the cumulative incidence of the primary outcome was significantly higher among patients treated with an antiplatelet and apixaban (HR 3.5, 95% CI: 1.0-12; p = 0.048). CONCLUSION: Apixaban monotherapy appears safe for the prevention of further adverse events in the Stenosis group patients similar to the No stenosis group patients. Concomitant use of an antiplatelet might not be favorable in patients with stenosis.

Association between body mass index and long-term clinical outcomes in patients with non-valvular atrial fibrillation taking oral anticoagulants.

BACKGROUND AND AIMS: The association between body mass index (BMI) and clinical outcomes of patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are controversial, and we thus analyzed the large registry data to elucidate them. METHODS AND RESULTS: We conducted a historical cohort study at 71 centers in Japan and included outpatients with NVAF taking vitamin K antagonists (VKAs). Physicians in charge could change VKAs to direct OACs based on their judgement during follow-up period. We categorized patients into four BMI groups (kg/m2): underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (30 ≤ BMI). The effects of each BMI group relative to the normal weight group on clinical outcomes consisting of all-cause death, ischemic events, and bleeding events were estimated using Cox proportional hazard models adjusting for potential confounders. We also constructed restricted cubic spline regression model adjusted by multivariable Cox proportional hazard models. We included 6927 patients consisting of an underweight (n = 386), normal weight (n = 3785), overweight (n = 2174), and obese (n = 582) groups. The median follow-up period was 3.9 years. In the underweight group, the adjusted hazard ratios (HRs) for all-cause death and ischemic events were 1.75 (1.30-2.34) and 1.61 (1.04-2.50). The HR for all-cause death was 0.63 (0.49-0.82) in the overweight group. Restricted cubic spline regression models confirmed that lower BMI showed significantly higher risks for all-cause death and ischemic events. CONCLUSION: Among NVAF patients taking OACs, underweight patients had higher risks of all-cause death and ischemic events than other patients. Overweight patients had lower risk of all-cause death.

Difference in the cumulative incidence of aneurysmal occlusion by Flow Re-direction Endoluminal Device and Pipeline Embolization Device in the treatment of unruptured internal carotid artery aneurysms: a propensity score-matched cohort study.

The introduction of flow diverters (FDs) has represented a paradigm shift in the management of unruptured cerebral aneurysms (UCA). Flow Re-direction Endoluminal Devices (FREDs) and Pipeline Embolization Devices (PEDs) have gained widespread popularity. We aimed to investigate the cumulative incidence of aneurysm occlusion. A total of 195 patients with 199 UCAs were analyzed retrospectively. The outcomes were aneurysmal occlusion during the follow-up, a modified Rankin Scale score of 0-2 at 90 days, additional treatment, major stroke, and steno-occlusive events of FD. Propensity score-matched analysis was performed, controlling for age, sex, aneurysmal size, and location of the internal carotid artery (ICA) aneurysm. Non-ICA aneurysms were excluded from matching. During the follow-up period (median, 366 days), complete and satisfactory aneurysmal occlusions were observed in 128 (68%) and 148 (78%) of 189 UCAs in the unmatched cohort. The 142 (71 each) propensity score-matched cohort was complied. The FRED group had a higher cumulative incidence of ICA aneurysm occlusion (complete: HR 2.7, 95% CI 1.4-5.1, p = 0.0025; satisfactory: HR 2.4, 95% CI 1.1-5.2, p = 0.025). The proportion of additional treatment was significantly smaller in the FRED group (OR 0.077, 95% CI 0.010-0.57, p = 0.0007). Other outcomes showed no significant differences. Propensity score-matched analysis indicated that FRED might have a higher cumulative incidence of aneurysmal occlusion in the treatment of unruptured ICA aneurysms. Whether a cumulative incidence of aneurysmal occlusion may differ by the type of FDs warrants further investigation.

Identifying large vessel occlusion using the hyperdense artery sign in patients treated with mechanical thrombectomy.

OBJECTIVES: The hyperdense artery sign on non-contrast computed tomography-reconstructed images is useful for identifying large vessel occlusion in acute ischemic stroke. This study aimed to assess its efficacy in patients with large vessel occlusion treated with mechanical thrombectomy. MATERIALS AND METHODS: This retrospective and prospective single-centered study from June 2019 to May 2021 evaluated the use of non-contrast computed tomography-reconstructed images for detecting hyperdense artery sign to identify large vessel occlusion from June 2020 to May 2021. We registered consecutive potential candidates for mechanical thrombectomy due to suspected stroke and assessed the accuracy of hyperdense artery sign on non-contrast computed tomography-reconstructed images for large vessel occlusion in the hyperacute setting. Non-contrast computed tomography images were reconstructed into maximum intensity projection images with iterative reconstruction algorithms to detect hyperdense artery signs. We compared the door-to-puncture time and functional outcome at 90 days before and after employing non-contrast computed tomography-reconstructed images in patients with large vessel occlusion treated with mechanical thrombectomy. RESULTS: The cohort included 82 patients, wherein 47 were treated with mechanical thrombectomy. The sensitivity (96%) and specificity (94%) of hyperdense artery sign on non-contrast computed tomography-reconstructed images for large vessel occlusion were performed. The door-to-puncture time was significantly shortened after using non-contrast computed tomography-reconstructed images (49 versus 28 min, p = 0.001), but the functional outcome at 90 days remained unchanged. CONCLUSIONS: Non-contrast computed tomography-reconstructed images, as a vascular imaging tool for mechanical thrombectomy, can reduce workflow time in hospitals by identifying large vessel occlusion with high sensitivity and specificity.

Outcomes of Large Vessel Occlusion Stroke in Patients Aged ≥90 Years.

BACKGROUND AND PURPOSE: Outcomes in patients ≥90 years of age with stroke due to large vessel occlusion were compared between endovascular therapy (EVT) and medical management. METHODS: Of 2420 acute ischemic stroke patients with large vessel occlusion in a prospective, multicenter, nationwide registry in Japan, patients aged ≥90 years with occlusion of the internal carotid artery or M1 segment of the middle cerebral artery were included. The primary effectiveness outcome was a favorable outcome at 3 months, defined as achieving a modified Rankin Scale score of 0 to 2 or return to at least the prestroke modified Rankin Scale score at 3 months. Safety outcomes included symptomatic intracranial hemorrhage within 72 hours after onset. Intergroup biases were adjusted by multivariable adjustment with inverse probability of treatment weighting. RESULTS: A total of 150 patients (median age, 92 [interquartile range, 90-94] years; median prestroke modified Rankin Scale score, 2 [interquartile range, 0-4]) were analyzed. EVT was performed in 49 patients (32.7%; mechanical thrombectomy, n=43). The EVT group showed shorter time from onset to hospital arrival (P=0.03), higher Alberta Stroke Program Early CT Score (P<0.01), and a higher rate of treatment with intravenous thrombolysis (P<0.01) than the medical management group. The favorable outcome was seen in 28.6% of the EVT group and 6.9% of the medical management group (P<0.01). EVT was associated with the favorable outcome (adjusted odds ratio, 8.44 [95% CI, 1.88-37.97]). Rates of symptomatic intracranial hemorrhage were similar between the EVT group (0.0%) and the medical management group (3.9%; P=0.30). CONCLUSIONS: Patients who underwent EVT showed better functional outcomes than those with medical management without increased symptomatic intracranial hemorrhages. Given proper patient selection, withholding EVT solely on the basis of the age of patients may not offer the best chance of good outcome. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02419794.

Association of Admission Hyperglycemia with Clinical Outcomes in Japanese Patients with Acute Large Vessel Occlusion Stroke: A post hoc Analysis of the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2.

INTRODUCTION: Admission hyperglycemia is an indicator of poor functional prognosis in acute stroke, but investigations of its prevalence and effects on the outcomes of acute large vessel occlusion in real-world, large-scale studies are limited, especially in Asian population. OBJECTIVE: We aimed to elucidate the relationship between admission hyperglycemia and outcomes in a prospective multicenter registry in Japan. METHODS: We analyzed data from the Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism (RESCUE) Japan Registry 2, which was a prospective, multicenter registry that enrolled patients from 46 centers in Japan. Admission hyperglycemia was defined as blood glucose level >140 mg/dL. The relationships between clinical outcomes and admission hyperglycemia were analyzed in all 1,932 assessable patients. A favorable functional outcome, defined as a modified Rankin Scale score of 0-2 at day 90, as well as mortality within 90 days and symptomatic intracranial hemorrhage (SICH) within 72 h, was analyzed. We performed subgroup analyses of the adjusted variables to investigate the association between hyperglycemia and favorable outcome in relation to each variable. RESULTS: Admission hyperglycemia was present in 687 (35.6%) of the assessable patients and in 420 (26.9%) of the 1,561 patients without diabetes. A favorable outcome was significantly less frequent in the hyperglycemia group than in the no-hyperglycemia group (33.2% vs. 47.6%, adjusted odds ratio [OR]: 0.60, 95% confidence interval [CI]: 0.47-0.76). The mortality rates were 12.8% and 6.8% in the hyperglycemia and no-hyperglycemia groups, respectively. The incidence of SICH within 72 h was higher in the hyperglycemia group than in the no-hyperglycemia group (4.4% vs. 1.9%, adjusted OR: 2.54, 95% CI: 1.36-4.82). Hyperglycemia was associated with unfavorable outcomes in almost all subgroups. CONCLUSIONS: Admission hyperglycemia in Japanese patients with large vessel occlusion stroke is associated with an unfavorable functional outcome at 90 days, mortality within 90 days, and the occurrence of SICH within 72 h.

Impact of Procedure Time on Clinical Outcomes of Patients Who Underwent Endovascular Therapy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The time from onset to reperfusion is associated with clinical outcomes in acute ischemic stroke due to large vessel occlusion (LVO); nevertheless, the time limit of the continuing procedure remains unclear. We analyzed the relationship between procedure time and clinical outcomes in patients with LVO who underwent endovascular treatment (EVT). METHODS: We assessed 1,247 patients who underwent EVT for LVO. Data were obtained from our multicenter registry, and patients were included if data on procedure time were available. Multivariate analysis was performed to assess the impact of procedure time on clinical outcomes using the following parameters: favorable outcome (the modified Rankin score of 0-2 at 90 days), mortality within 90 days, symptomatic intracranial hemorrhage within 72 h after stroke onset, and procedure-related complications. RESULTS: The rate of favorable outcomes linearly decreased with increasing procedure time, but there was no linear relationship between procedure time and other outcomes. The adjusted odds ratio for 30-minute delay in procedure time was 0.76 (95% confidence interval, 0.68-0.84) for favorable outcome, 1.15 (0.97-1.36) for mortality, 1.08 (0.87-1.33) for symptomatic intracranial hemorrhage, and 0.92 (0.75-1.16) for complications. Significant interactions in the effect of procedure time on favorable outcome were observed between the subgroups stratified by age (≥75 or <75 years). Younger patients had a greater deleterious effect of delayed reperfusion. CONCLUSIONS: Increasing procedure time was associated with less favorable outcomes, but not with the rate of mortality, symptomatic intracerebral hemorrhage, or complications in our cohort.

Differences in Acute Ischemic Stroke Management and Prognosis between Multiple Large-Vessel Occlusion and Single Large-Vessel Occlusion: Subanalysis of the RESCUE-Japan Registry 2.

INTRODUCTION: The management and prognosis of acute ischemic stroke due to multiple large-vessel occlusion (LVO) (MLVO) are not well scrutinized. We therefore aimed to elucidate the differences in patient characteristics and prognosis of MLVO and single LVO (SLVO). METHODS: The Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) enrolled 2,420 consecutive patients with acute LVO who were admitted within 24 h of onset. We compared patient prognosis between MLVO and SLVO in the favorable outcome, defined as a modified Rankin Scale (mRS) score ≤2, and in mortality at 90 days by adjusting for confounders. Additionally, we stratified MLVO patients into tandem occlusion and different territories, according to the occlusion site information and also examined their characteristics. RESULTS: Among the 2,399 patients registered, 124 (5.2%) had MLVO. Although there was no difference between the 2 groups in terms of hypertension as a risk factor, the mean arterial pressure on admission was significantly higher in MLVO (115 vs. 107 mm Hg, p = 0.004). MLVO in different territories was more likely to be cardioembolic (42.1 vs. 10.4%, p = 0.0002), while MLVO in tandem occlusion was more likely to be atherothrombotic (39.5 vs. 81.3%, p < 0.0001). Among MLVO, tandem occlusion had a significantly longer onset-to-door time than different territories (200 vs. 95 min, p = 0.02); accordingly, the tissue plasminogen activator administration was significantly less in tandem occlusion (22.4 vs. 47.9%, p = 0.003). However, interestingly, the endovascular thrombectomy (EVT) was performed significantly more in tandem occlusion (63.2 vs. 41.7%; adjusted odds ratio [aOR], 2.3; 95% confidence interval [CI], 1.1-5.0). The type of MLVO was the only and significant factor associated with EVT performance in multivariate analysis. The favorable outcomes were obtained less in MLVO than in SLVO (28.2 vs. 37.1%; aOR, 0.48; 95% CI, 0.30-0.76). The mortality rate was not significantly different between MLVO and SLVO (8.9 vs. 11.1%, p = 0.42). DISCUSSION/CONCLUSION: The prognosis of MLVO was significantly worse than that of SLVO. In different territories, we might be able to consider more aggressive EVT interventions.

Effect of concomitant antiplatelet therapy on ischemic and hemorrhagic events in patients taking oral anticoagulants for nonvalvular atrial fibrillation in daily clinical practice.

PURPOSE: Antiplatelet therapy (APT) is challenging in patients taking oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) with concomitant atherosclerotic diseases. We scrutinized the generalizability of recent randomized clinical trials showing OAC use alone was superior to OAC plus antiplatelet use in patients with NVAF and coronary artery diseases (CAD). METHODS: We conducted a historical multicenter registry at 71 centers in Japan. The inclusion criterion was taking OACs for NVAF. The exclusion criteria were mechanical heart valves or history of pulmonary thrombosis or deep vein thrombosis. Consecutive patients (N = 7826) were registered in February 2013 and were followed until February 2017. The co-primary endpoints were ischemic events and major bleedings. Secondary endpoints were ischemic stroke, hemorrhagic stroke, and all-cause mortality. RESULTS: The mean patient age was 73 years; 67% were men. Antiplatelets were administered in 25% of patients and 27% had history of CAD. Cumulative incidences of ischemic events and major bleedings at 4 years were 5.9% and 9.6% in the APT group and 5.3% and 7.0% in the No-APT group, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of the APT group for ischemic events and major bleedings were 1.12 (0.84-1.49) and 1.26 (1.01-1.57), respectively. The adjusted HRs (95% CIs) for ischemic stroke, hemorrhagic stroke, and all-cause mortality were 1.16 (0.86-1.57), and 1.31 (0.70-2.48), and 1.02 (0.82-1.26), respectively. CONCLUSIONS: APT in patients taking OACs for NVAF did not prevent ischemic events but significantly increased major bleedings in the real-world setting.

Simplified Prehospital Prediction Rule to Estimate the Likelihood of 4 Types of Stroke: The 7-Item Japan Urgent Stroke Triage (JUST-7) Score.

OBJECTIVE: Prehospital prediction models to estimate the likelihood of several types of stroke (large vessel occlusion [LVO], intracranial hemorrhage [ICH], and subarachnoid hemorrhage [SAH], and other types of stroke) should be useful to transfer those with suspected stroke to appropriate facilities. We recently reported Japan Urgent Stroke Triage (JUST) score with 21 items had excellent predictive abilities, and we further tried to simplify the score with parsimonious items and comparable predictive abilities. METHODS: We conducted historical and prospective multicenter cohort studies at 8 centers from June 2015 to March 2018. We developed the prediction rules with select variables from JUST score for LVO, ICH, SAH and other types of stroke in 2236 patients with suspected stroke in historical derivation cohort. We validated the developed prediction rules in 964 patients in prospective validation cohort. RESULTS: There were 1150 stroke, including 235 LVO, 352 ICH, 107 SAH and 456 other types of stroke in the derivation cohort. We developed the scores with 7 items (high blood pressure, arrhythmia, conjugate deviation, headache, dysarthria, disturbance of consciousness, paralysis of upper limbs) and the developed scores had area under the receiver-operating curve (AUC) of 0.84 for any type of stroke, 0.89 for LVO, 0.79 for ICH, and 0.90 for SAH in the derivation cohort. There were 490 stroke, including 102 LVO, 138 ICH, 28 SAH and 222 other types of stroke in the validation cohort. The scores well discriminated these strokes in the validation cohort (AUC of 0.76 for any type of stroke; 0.81 for LVO, 0.73 for ICH, and 0.85 for SAH). CONCLUSIONS: The simplified 7-item JUST (JUST-7) score had good predictive ability and can help healthcare providers to estimate the likelihood of different types of stroke and decide the referral hospital.

Outcome of retreatment for recurrent saccular cerebral aneurysms: a propensity score-matched analysis.

Although endovascular or surgical treatment has been performed for preventing the rupture of saccular cerebral aneurysms (sCA), in some patients, the aneurysms may recur and require retreatment. We aimed to investigate the clinical and radiological outcomes of treating recurrent sCA. We retrospectively evaluated the data of 52 patients with 60 recurrent sCAs who were retreated and 1534 patients with 1817 sCAs who received initial treatment. The primary outcome was a recurrence of the aneurysm. Secondary outcomes were an additional treatment, rupture after treatment, and a neurological worsening, which was defined as an increase of 1 or more scores using the modified Rankin Scale at 12-month. Safety outcomes included postoperative ischemic and hemorrhagic complications. We compiled the 120 (60 each) propensity score-matched cohort based on a propensity score for the treatment of recurrent sCA. In the propensity score-matched cohort, recurrence after treatment was observed in 25% and 6.7% of cases in the retreatment and initial treatment groups, respectively. The odds ratio of recurrence after treatment was 4.7 (95% CI, 1.4-15; P = 0.011). The secondary and safety outcomes were not significantly different between the two groups. This study showed that the treatment of recurrent sCA was a risk factor for recurrence after treatment but not for additional treatment, rupture after treatment, or neurological worsening. Although decision-making regarding the treatment varies depending on the institutional protocols and personal experience of the physicians, endovascular or surgical retreatment could be performed without hesitation.

Wall Redness of Enlarged Unruptured Cerebral Aneurysm.

OBJECTIVES: The wall of enlarged unruptured cerebral aneurysm (EUCA) is thought to be reddish, thin, and fragile. This study aimed to evaluate the EUCA wall redness based on quantitative signal intensity method and to compare the clinical and radiological characteristics between EUCA and non-EUCA. MATERIALS & METHODS: In this retrospective analysis, red (R), green (G), blue (B), and RGB signal intensities of aneurysm were quantitatively measured using an intraoperative digital picture in 150 cases. Color intensities were measured by two independent investigators. Aneurysm redness was defined as an R/RGB ratio since the brightness of the operative field differed by each surgery or angle of the microscope. RESULTS: The median aneurysm size was 4.9 mm (IQR 3.9-5.9 mm). Median color intensity of R, G, B, RGB, and R/RGB ratio were 206 (185-215), 129 (107-150), 136 (115-157), 157 (140-174), and 1.26 (1.20-1.38), respectively. The intraclass correlation coefficient for R/RGB ratio was 0.73 (P<0.0001). The proportion of female sex was significantly higher for EUCA (p = 0.019). Median R/RGB ratio in GUCA was significantly larger than that of non-EUCA (OR 1.25, 95% CI 1.19-1.35) (p = 0.035). Even after adjustment of female sex, a R/RGB ratio ≧1.36 was related to EUCA (OR 3.02, 95% CI 1.30-7.02). CONCLUSIONS: The present study showed that a R/RGB ratio could be calculated easily and a larger R/RGB ratio was related to EUCA. When EUCA is managed by surgical treatment, more careful manipulation should be needed compared to non-EUCA due to a "red" wall of EUCA.

Relationship Between Acute Neurological Function and Long-Term Prognosis in Patients with Large Arterial Occlusions.

OBJECTIVES: To clarify the relationship between early neurological symptoms and long-term functional outcomes of acute ischemic stroke, which would be beneficial for patient management and determining clinical study criteria of novel therapeutic interventions. MATERIALS AND METHODS: We retrieved data from the Recovery by Endovascular Salvage for Cerebral Ultra-acute Embolism Japan Registry 2 (RESCUE-Japan Registry 2) and investigated the association between 24- and 72-hour National Institutes of Health Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) scores, stratified by the site of occlusion (carotid or vertebrobasilar circulatory large arterial occlusion [ACO or PCO, respectively]) and endovascular recanalization therapy (EVT) performance. We examined the correlation using Spearman's rank correlation coefficient (rho). Predictive accuracies of 24- and 72-hour NIHSS scores for good outcomes at 90 days (defined as mRS score of 0-2) were evaluated by receiver operating characteristic (ROC) analyses and the corresponding areas under the curves (AUCs). RESULTS: Among the 2420 patients, 1745 had ACO (971 with EVT, 774 without EVT) and 263 had PCO (127 with EVT, 136 without EVT). The 24- and 72-hour NIHSS scores were significantly associated with 90-day mRS scores and accurately predicted good outcomes (all rhos ≥0.76, all AUCs ≥0.86). In the ACO group, there were differences in rho and AUC depending on EVT performance and the time from onset to NIHSS acquisition, but no differences were observed in the PCO group. CONCLUSIONS: EVT performance and time frame should be considered when determining the criteria of novel therapeutic interventions, especially for patients with ACO.