High brain natriuretic peptide level is associated with severe stroke in patients taking oral anticoagulants: A sub-analysis of the PASTA registry study.

BACKGROUND: Brain natriuretic peptides (BNP) are an important diagnostic and prognostic marker in patients with heart failure. However, the relationship between BNP levels and stroke severity in patients with atrial fibrillation (AF) remains unelucidated. In this study, we aimed to investigate the association between stroke severity at admission and BNP levels. METHODS: In this prospective observational study, we used data from 513 patients with AF and acute ischemic stroke treated with oral anticoagulants (OAC) registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study. The patients were divided into two groups: high-BNP (≥200 pg/mL) and low-BNP level (<200 pg/mL) groups. We compared the clinical characteristics between the two groups and determined the effect of BNP levels on stroke severity on admission. RESULTS: Among the 513 enrolled patients, 248 (females, n = 30; median age, 82 years) and 265 (females, n = 76; median age, 71 years) were assigned to the high- and low-BNP level groups, respectively. The high-BNP level group had a higher proportion of patients with severe stroke (National Institutes of Health Stroke Scale score, ≥10) on admission (49.2% vs. 32.8%, p = 0.002) and major vessel occlusion (57.5% vs. 39.2%, p < 0.0001) than that had by the low-BNP level group. Multivariate analysis showed that high BNP level was independently associated with severe stroke on admission (odds ratio 1.07, 95% confidence interval 1.00-1.15; p = 0.0478). CONCLUSIONS: High BNP level compared with low BNP level was associated with severe stroke and major vessel occlusion, even before OAC treatment.

High pre-stroke CHADS2 score predicts unfavorable functional outcome in acute cardioembolic stroke patients prescribed oral anticoagulant therapy: A sub-analysis of the PASTA registry study.

BACKGROUND AND PURPOSE: The impact of CHADS2 score on outcome in patients with stroke taking an oral anticoagulant (OAC) has not yet been fully elucidated. We investigated the association between pre-stroke CHADS2 score and outcome at discharge in patients with acute cardioembolic (CE) stroke due to atrial fibrillation (AF) who were prescribed OAC. METHODS: The data of 548 OAC-treated patients with AF and CE stroke who were registered in the multicenter Prospective Analysis of Stroke patients Taking oral Anticoagulants (PASTA) study were analyzed. High CHADS2 score was defined as a pre-stroke CHADS2 score ≥2. Unfavorable outcome was defined as a modified Rankin scale (mRS) of 3-6. The impacts of pre-stroke CHADS2 score on outcome at discharge were evaluated using multiple logistic regression analysis. RESULT: A high CHADS2 score was found in 472/548 patients and unfavorable outcome was found in 330/548 patients. In patients with unfavorable outcome, age, male sex, pre-stroke CHADS2 score, initial National Institute Health Stroke Scale (NIHSS) score, and glucose level on admission were significantly higher, whereas creatinine clearance and body weight were significantly lower, than those with favorable outcome (each p < 0.001). Multivariate logistic regression analysis indicated that high CHADS2 score (OR 2.18, 95 %CI 1.08-4.42, p = 0.031), pre-stroke mRS (OR 2.21, 95 %CI 1.69-2.67, p < 0.001), and initial NIHSS score (OR 1.19, 95 %CI 1.17-1.24, p < 0.001) were independently associated with unfavorable outcome. CONCLUSION: Pre-stroke CHADS2 score was associated with poor outcome in patients with cardioembolic stroke due to AF, even in those taking OAC.

Resumption of oral anticoagulation in patients with non-valvular atrial fibrillation after intracerebral hemorrhage: A sub-analysis of the PASTA registry study.

PURPOSE: To investigate the rate and timing of oral anticoagulant (OAC) resumption and its safety in patients after intracerebral hemorrhage (ICH) in current clinical practice in Japan. METHODS: We conducted a sub-analysis of the PASTA registry, an observational, multicenter registry of 1043 patients with stroke receiving OACs in Japan, by including patients with ICH on OAC treatment for non-valvular atrial fibrillation (NVAF). The clinical characteristics of the patients in the resumption and non-resumption groups, rate and timing of OAC resumption, its safety, and switching of OACs after ICH were investigated. RESULTS: Of the 160 patients (women, n = 52; median age, 77 years) included, OACs were resumed in 108 (68%) at a median of 7 days (interquartile range, 4-11) after acute ICH onset. The non-resumption group had higher rates of hematoma expansion (21.2% vs. 7.4%; P = 0.0118) and modified Rankin Scale (mRS) scores at discharge (4 (Suda et al., 2019; Steiner et al., 2014 [3, 4]) vs. 4 (Suda et al., 2019; Steiner et al., 2014; Pasquini et al., 2014 [3-5]); P = 0.0302}. The resumption rate in the mRS 0-4 group was higher than that in the mRS 5 group (75.2% vs. 46.5%; P = 0.00006). The number of days to resumption after ICH onset was longer in the mRS 5 than that in the mRS 0-4 group (median 12 days vs. 7 days, P = 0.0065). There were no significant differences in new-onset ICH, symptomatic hematoma expansion, or gastrointestinal bleeding between groups (P > 0.05). CONCLUSIONS: Early resumption of OAC for NVAF in patients after ICH appeared to be safe. Expected functional outcomes at discharge were associated with OAC resumption and with the timing of resumption. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Vitamin K antagonists but not non-vitamin K antagonists in addition on antiplatelet therapy should be associated with increase of hematoma volume and mortality in patients with intracerebral hemorrhage: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prior concomitant use of vitamin K antagonists (VKAs) and antiplatelet (AP) therapy increase the hematoma volume and mortality compared with VKA monotherapy in patients with intracranial hemorrhage (ICH). However, the prior concomitant use of non-vitamin K oral antagonists (NOACs) and AP has not been clarified. METHODS: We conducted a PASTA registry study, which was an observational, multicenter, registry of 1043 patients with stroke receiving oral anticoagulants (OACs) in Japan. In the present study, ICH from the PASTA registry was used to analyze the clinical characteristics including mortality among the four groups (NOAC, VKA, NOAC and AP, and VKA and AP) using univariate and multivariate analyses. RESULTS: Among the 216 patients with ICH, 118 (54.6%), 27 (12.5%), 55 (25.5%), 16 (7.4%) were taking NOAC monotherapy, NOAC and AP, VKA, and VKA and AP, respectively. In-hospital mortality rates were the highest in VKA and AP (31.3%) than in NOACs (11.9%), NOACs and AP (7.4%), and VKA (7.3%). Multivariate logistic regression analysis demonstrated that the concomitant use of VKA and AP (odds ratio [OR], 20.57; 95% confidence interval [CI], 1.75-241.75, p = 0.0162), initial National Institutes of Health Stroke Scale score (OR, 1.21; 95%CI, 1.10-1.37, p < 0.0001), hematoma volume (OR, 1.41; 95%CI, 1.10-1.90, p = 0.066), and systolic blood pressure (OR, 1.31; 95%CI, 1.00-1.75, p = 0.0422) were independently associated with in-hospital mortality. CONCLUSIONS: Although VKA in addition to AP therapy could increase the in-hospital mortality, NOAC and AP did not increase the hematoma volume, stroke severity, or mortality compared to NOAC monotherapy.

Safety of recanalization therapy in patients with acute ischemic stroke on direct oral anticoagulants: A sub-analysis of PASTA registry study.

BACKGROUND: The safety of intravenous recombinant tissue plasminogen activator (rtPA) and mechanical thrombectomy (MT) in patients treated with direct oral anticoagulants (DOACs) before stroke has not been fully investigated. Therefore, we aimed to investigate the safety of recanalization therapy in patients receiving DOACs. METHODS: We assessed data from a prospective multicenter registry of patients with stroke, including those with acute ischemic stroke (AIS) treated with rtPA and/or MT who were administered DOACs. We evaluated the safety of recanalization considering the DOACs dosage and interval between the last DOAC intake and recanalization. RESULTS: The final analysis included 108 patients (women, n = 54; median age, 81 years; DOAC overdose, n = 7; appropriate dose, n = 74; and inappropriate low dose, n = 27). The rate of any ICH differed significantly among overdose-, appropriate dose-, and inappropriate-low dose DOACs groups (71.4, 23.0, and 33.3%, respectively; P = 0.0121), whereas no significant difference was observed in respect of symptomatic ICH (P = 0.6895). Multivariate analysis showed that the National Institutes of Health Stroke Scale score on admission (odds ratio [OR]: 1.06, 95% confidence interval [CI]: 1.01-1.11; P = 0.0267) and overdose-DOAC (OR: 8.40, 95% CI: 1.24-56.88; P = 0.0291) were independently associated with any ICH. No relationship was observed between the timing of the last DOAC intake and occurrence of ICH in patients treated with rtPA and/or MT (all P > 0.05). CONCLUSION: Recanalization therapy during DOAC treatment may be safe in selected patients with AIS, if it is performed >4 h after the last DOAC intake and the patient is not overdosed with DOACs. REGISTRATION: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Association between Living Conditions and the Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults.

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Rankin Scale ≥4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

Intravenous Alteplase at 0.6 mg/kg for Unknown Onset Stroke with Prior Antithrombotic Medication: THAWS Randomized Clinical Trial.

AIM: This study aimed to assess the potential effect of prior antithrombotic medication for thrombolysis in an unknown onset stroke. METHODS: This was a predefined sub-analysis of the THAWS trial. Stroke patients with a time last known well ＞4.5 h who had a DWI-fluid-attenuated inversion recovery mismatch were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg (alteplase group) or standard medical treatment (control group). Patients were dichotomized by prior antithrombotic medication. RESULTS: Of 126 patients (intention-to-treat population), 40 took antithrombotic medication (24 with antiplatelets alone, 13 with anticoagulants alone, and 3 with both), and the remaining 86 did not before stroke onset. Of these, 17 and 52 patients, respectively, received alteplase, and 23 and 34, respectively, had standard medical treatment. Antithrombotic therapy was initiated within 24 h after randomization less frequently in the alteplase group (12% vs. 86%, p＜0.01). Both any intracranial hemorrhage within 22-36 h (26% vs. 14%) and a modified Rankin Scale score of 0-1 at 90 days (good outcome) (47% vs. 48%) were comparable between the two groups. A good outcome was more common in the alteplase group than in the control group in patients with prior antithrombotic medication [relative risk (RR) 2.25, 95% confidence interval (CI) 1.02-4.99], but it tended to be less common in the alteplase group in those without (RR 0.69, 95% CI 0.46-1.03) (p＜0.01 for interaction). The frequency of any intracranial hemorrhage did not significantly differ between the two groups in any patients dichotomized by prior antithrombotic medication. CONCLUSION: Alteplase appears more beneficial in patients with prior antithrombotic medication.

Sustained atrial fibrillation is related to a higher severity of stroke in patients taking direct oral anticoagulants.

BACKGROUND: Atrial fibrillation (AF) includes paroxysmal and sustained (persistent or permanent) AF, and both forms are considered risk factors for ischemic stroke. This study aimed to investigate the differences in stroke severity at admission between patients with paroxysmal AF and sustained AF when treated with direct oral anticoagulants (DOACs). METHODS: Using data from DOAC-treated 300 nonvalvular patients with AF and acute anterior circulation stroke who were registered in the Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants study, patients were divided into two groups, namely, paroxysmal AF and sustained AF. We compared the clinical characteristics between the two groups and determined the effect of these two types of AF on stroke severity on admission. RESULTS: Of 300 patients, 246 (males, n = 149; median age, 80 years) and 54 (males, n = 32; median age, 78 years) were assigned to the sustained AF and paroxysmal AF groups, respectively. The sustained AF group had a higher proportion of severe stroke (National Institutes of Health Stroke Scale score, >20) on admission (22.0% vs. 5.7%, p = 0.006) and internal carotid artery occlusion (11.4% vs. 1.9%, p = 0.03) compared to the paroxysmal AF group. Multivariate analysis showed that sustained AF was independently associated with severe stroke on admission (odds ratio 4.31, 95% confidence interval 1.24-15.0, p = 0.02). CONCLUSIONS: Sustained AF was associated with a higher severity of stroke accompanied with major vessel occlusion than paroxysmal AF, even prior to DOACs treatment. Registration https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034958.

Prior direct oral anticoagulant dosage and outcomes in patients with acute ischemic stroke and non-valvular atrial fibrillation: A sub-analysis of PASTA registry study.

BACKGROUND AND PURPOSE: Prescribing under-dose direct oral anticoagulants (DOACs) for non-valvular atrial fibrillation (NVAF) is alerted to increase cardiovascular events or death. However, the association between dose selection of DOACs and the clinical course remains unclear. This study aimed to propose a novel criterion for selecting the DOAC dose and investigate clinical characteristics of ischemic stroke (IS) under this criterion. METHODS: We assessed the pooled prospective multicenter registry data of stroke patients taking anticoagulant agents, including IS patients with NVAF and prior DOAC usage. The recommended dose according to the reduction criteria of each DOAC and the selected dose were identified for each patient, and patients were categorized into four groups: no alternative low-dose, selecting low-dose appropriately with all DOACs applicable for reduction criteria; selected low-dose, selecting low-dose appropriately or inappropriately despite at least one DOAC inapplicable for reduction criteria; selected standard-dose, appropriate standard-dose use; and absolute over-dose, inappropriate standard-dose regardless of criteria. We investigated the effects of dose selection of DOACs on short-term poor functional outcomes. RESULTS: 322 patients were included in the analysis. The prevalence of no alternative low-dose, selected low-dose, selected standard-dose, and absolute over-dose was 74 (23%), 144 (45%), 89 (27%), and 15 (5%), respectively. Multivariable analysis found that the selected low-dose group showed significantly poorer functional outcomes than the selected standard-dose group only in patients without renal dysfunction (OR, 2.60; 95% CI, 1.17-6.00; P = 0.0186). CONCLUSIONS: Selecting a low dose DOAC might be associated with poor functional outcomes in patients without renal dysfunction.

Characteristics of Ischemic Versus Hemorrhagic Stroke in Patients Receiving Oral Anticoagulants: Results of the PASTA Study.

Objective Limited data exist regarding the comparative detailed clinical characteristics of patients with ischemic stroke (IS)/transient ischemic attack (TIA) and intracerebral hemorrhage (ICH) receiving oral anticoagulants (OACs). Methods The prospective analysis of stroke patients taking oral anticoagulants (PASTA) registry, a multicenter registry of 1,043 stroke patients receiving OACs [vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulant (NOACs)] across 25 medical institutions throughout Japan, was used. Univariate and multivariable analyses were used to analyze differences in clinical characteristics between IS/TIA and ICH patients with atrial fibrillation (AF) who were registered in the PASTA registry. Results There was no significant differences in cardiovascular risk factors, such as hypertension, diabetes mellitus, dyslipidemia, smoking, or alcohol consumption (all p>0.05), between IS/TIA and ICH among both NOAC and VKA users. Cerebral microbleeds (CMBs) [odds ratio (OR), 4.77; p<0.0001] were independently associated with ICH, and high brain natriuretic peptide/N-terminal pro B-type natriuretic peptide levels (OR, 1.89; p=0.0390) were independently associated with IS/TIA among NOAC users. A history of ICH (OR, 13.59; p=0.0279) and the high prothrombin time-international normalized ratio (PT-INR) (OR, 1.17; p<0.0001) were independently associated with ICH, and a history of IS/TIA (OR, 3.37; 95% CI, 1.34-8.49; p=0.0101) and high D-dimer levels (OR, 2.47; 95% CI, 1.05-5.82; p=0.0377) were independently associated with IS/TIA among VKA users. Conclusion The presence of CMBs, a history of stroke, natriuretic peptide and D-dimer levels, and PT-INR may be useful for risk stratification of either IS/TIA or ICH development in patients with AF receiving OACs.

Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy.

BACKGROUND AND PURPOSE: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database. METHODS: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. RESULTS: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI (P=0.026) and core volume (P=0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33-30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87-43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients. CONCLUSIONS: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000011630.

Predicting the outcome of non-pharmacological treatment for patients with dementia-related mild cognitive impairment.

Dementia is a progressive cognitive syndrome, with few effective pharmacological treatments that can slow its progress. Hence, non-pharmacological treatments (NPTs) play an important role in improving patient symptoms and quality of life. Designing the optimal personalised NPT strategy relies on objectively and quantitatively predicting the treatment outcome. Magnetoencephalography (MEG) findings can reflect the cognitive status of patients with dementia, and thus potentially predict NPT outcome. In the present study, 16 participants with cognitive impairment underwent NPT for several months. Their cognitive performance was evaluated based on the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale - Cognitive at the beginning and end of the NPT period, while resting-state brain activity was evaluated using MEG during the NPT period. Our results showed that the spectral properties of MEG signals predicted the changes in cognitive performance scores. High frequency oscillatory intensity at the right superior frontal gyrus medial segment, opercular part of the inferior frontal gyrus, triangular part of the inferior frontal gyrus, post central gyrus, and angular gyrus predicted the changes in cognitive performance scores. Thus, resting-state brain activity may be a powerful tool in designing personalised NPT.

Risk factors, etiology, and outcome of ischemic stroke in young adults: A Japanese multicenter prospective study.

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; P>0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.

Multicenter Prospective Analysis of Stroke Patients Taking Oral Anticoagulants: The PASTA Registry - Study Design and Characteristics.

OBJECTIVES: The management of atrial fibrillation and deep venous thrombosis has evolved with the development of direct oral anticoagulants (DOAC), and oral anticoagulant (OAC) might influence the development or clinical course in both ischemic and hemorrhagic stroke. However, detailed data on the differences between the effects of the prior prescription of warfarin and DOAC on the clinical characteristics, neuroradiologic findings, and outcome of stroke are limited. DESIGN: The prospective analysis of stroke patients taking anticoagulants (PASTA) registry study is an observational, multicenter, prospective registry of stroke (ischemic stroke, transient ischemic attack, and intracerebral hemorrhage) patients receiving OAC in Japan. This study is designed to collect data on clinical background characteristics, drug adherence, drug dosage, neurological severity at admission and discharge, infarct or hematoma size, acute therapy including recanalization therapy or reverse drug therapy, and timing of OAC re-initiation. Patient enrollment started in April 2016 and the target patient number is 1000 patients. CONCLUSIONS: The PASTA prospective registry should identify the status of stroke patients taking OAC in the current clinical practice in Japan.

Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke: A Randomized Clinical Trial and Meta-analysis.

IMPORTANCE: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that a systolic blood pressure (BP) target less than 120 mm Hg was superior to less than 140 mm Hg for preventing vascular events. This trial excluded patients with prior stroke; therefore, the ideal BP target for secondary stroke prevention remains unknown. OBJECTIVE: To assess whether intensive BP control would achieve fewer recurrent strokes vs standard BP control. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial (RCT) of standard vs intensive BP control in an intent-to-treat population of patients who had a history of stroke. Patients were enrolled between October 20, 2010, and December 7, 2016. For an updated meta-analysis, PubMed and the Cochrane Central Library database were searched through September 30, 2018, using the Medical Subject Headings and relevant search terms for cerebrovascular disease and for intensive BP lowering. This was a multicenter trial that included 140 hospitals in Japan; 1514 patients who had a history of stroke within the previous 3 years were approached, but 234 refused to give informed consent. INTERVENTIONS: In total, 1280 patients were randomized 1:1 to BP control to less than 140/90 mm Hg (standard treatment) (n = 640) or to less than 120/80 mm Hg (intensive treatment) (n = 640). However, 17 patients never received intervention; therefore, 1263 patients assigned to standard treatment (n = 630) or intensive treatment (n = 633) were analyzed. MAIN OUTCOMES AND MEASURES: The primary outcome was stroke recurrence. RESULTS: The trial was stopped early. Among 1263 analyzed patients (mean [SD] age, 67.2 [8.8] years; 69.4% male), 1257 of 1263 (99.5%) completed a mean (SD) of 3.9 (1.5) years of follow-up. The mean BP at baseline was 145.4/83.6 mm Hg. Throughout the overall follow-up period, the mean BP was 133.2/77.7 (95% CI, 132.5-133.8/77.1-78.4) mm Hg in the standard group and 126.7/77.4 (95% CI, 125.9-127.2/73.8-75.0) mm Hg in the intensive group. Ninety-one first recurrent strokes occurred. Nonsignificant rate reductions were seen for recurrent stroke in the intensive group compared with the standard group (hazard ratio [HR], 0.73; 95% CI, 0.49-1.11; P = .15). When this finding was pooled in 3 previous relevant RCTs in a meta-analysis, the risk ratio favored intensive BP control (relative risk, 0.78; 95% CI, 0.64-0.96; P = .02; absolute risk difference, -1.5%; 95% CI, -2.6% to -0.4%; number needed to treat, 67; 95% CI, 39-250). CONCLUSIONS AND RELEVANCE: Intensive BP lowering tended to reduce stroke recurrence. The updated meta-analysis supports a target BP less than 130/80 mm Hg in secondary stroke prevention. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01198496.

Correlation between the Occlusion Site and Clinical Outcome after Acute Ischemic Stroke.

OBJECTIVE: The significance of early mild clinical improvement after intravenous tissue plasminogen activator (IVtPA) treatment is unclear. Therefore, we examined whether the timing of clinical improvement after IVtPA predicted the clinical outcome at 3 months. METHODS: Consecutive patients with acute cerebral infarction in the anterior circulation who received IVtPA treatment within 3 hours of the onset of symptoms were enrolled in the study. Patients were classified according to the timing of clinical improvement [early responder (ER), National Institutes of Health Stroke Scale (NIHSS) score improved ≥4 points or who had a score of 0 within 2 hours after IVtPA; late responder (LR), a similar improvement between 2 and 24 hours; and non-responder (NR)] and according to the arterial occlusion site (P group, internal carotid artery and proximal middle cerebral artery M1 region; and D group, distal M1 and M2). RESULTS: Ninety-three patients [median age, 74 (67-79) years; 54 men (58%); median NIHSS score, 11 (7-16)] were enrolled in the study. The P group consisted of 48 (52%) patients and the D group consisted of 45 (48%) patients. Thirty-eight patients (41%) were classified as ERs, 20 (22%) as LRs, and 35 (38%) as NRs. On a multivariate regression analysis, the P group [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.08-10.45; p=0.036] and NR (OR, 4.04; 95% CI, 1.29-14.27; p=0.016) were independent predictors of a poor outcome. ER (47%, p=0.01) and LR (45%, p=0.01) patients showed fewer poor outcomes than NR (77%) patients, but the rate did not differ significantly between the ER and LR patients. CONCLUSION: Early mild clinical recovery did not predict a good outcome. The occlusion site was a stronger predictor of clinical improvement after IVtPA administration.

Prediction of cerebrovascular reserve capacity by computed tomography perfusion using 320-row computed tomography.

BACKGROUND: Acetazolamide loading has been the "gold standard" for evaluating cerebrovascular reserve capacity (CVRC). However, life-threatening side effects of acetazolamide have recently been reported. The aim of the study was to identify alternative methods for evaluating CVRC. METHODS: We reviewed 6 patients who underwent both computed tomography perfusion (CTP) imaging and xenon CT (XeCT) imaging with and without acetazolamide loading during the same periods. The data were obtained as volume data using 320-row CT and applied to the automated region of interest-determining software and converted to standardized images. Correlations between CVRC and CTP parameters were analyzed by Pearson correlation coefficient analysis, and simple regression was used to assess the relationship between the data. When statistically significant, correlation between CVRC and any CTP data is identified, and cutoff points for CVRC 30% and 10% were calculated with receiver operating characteristic curves. RESULTS: Of 4 CTP parameters evaluated, statistically significant correlations were observed between time to peak (TTP) by CTP and CVRC (P < .0001, r = -.7228) calculated from XeCT. The regression line using CVRC as outcome variable (y) and using TTP as predictor variable (x) was y = -9.062x + 140.1. The cutoff value for the TTP for CVRC less than 10% was 12.56 seconds (sensitivity of 86% and specificity of 85%) and that for CVRC less than 30% was 9.34 seconds (sensitivity of 77% and specificity of 96%). CONCLUSIONS: TTP calculated from CTP data correlated well with the CVRC calculated from XeCT data. These results suggest that TTP calculated from CTP could be used to estimate CVRC in patients with occlusive cardiovascular disease.

Comparison of cerebral blood flow data obtained by computed tomography (CT) perfusion with that obtained by xenon CT using 320-row CT.

Cerebral blood flow (CBF) data obtained by computed tomography perfusion (CTP) imaging have been shown to be qualitative data rather than quantitative, in contrast with data obtained by other imaging methods, such as xenon CT (XeCT) imaging. Thus, interpatient comparisons of CBF values themselves obtained by CTP may be inaccurate. In this study, we have compared CBF ratios as well as CBF values obtained from CTP-CBF data to those obtained from XeCT-CBF data for the same patients to determine CTP-CBF parameters that can be used for interpatient comparisons. The data used in the present study were obtained as volume data using 320-row CT. The volume data were applied to an automated region of interest-determining software (3DSRT, version 3.5.2 ) and converted to 59 slices of 2 mm interval standardized images. In the present study, we reviewed 10 patients with occlusive cerebrovascular diseases (CVDs) undergoing both CTP and XeCT in the same period. Our study shows that ratios of CBF measurements, such as hemodynamic stress distribution (perforator-to-cortical flow ratio of middle cerebral artery [MCA] region) or the left/right ratio for the region of the MCA, calculated using CTP data have been shown to correlate well with the same ratios calculated using XeCT data. These results suggest that such CBF ratios could be useful for generating interpatient comparisons of CTP-CBF data obtained by 320-row CT among patients with occlusive CVD.

Aberrant NF-kappaB activity is critical in focal necrosis formation of human glioblastoma by regulation of the expression of tissue factor.

Focal necrosis is a key pathologic feature that distinguishes glioblastoma from lower grade glioma. The presence of necrosis in a glioblastoma could promote its rapid growth and clinical progression. Focal necrosis of glioblastoma seems to be associated with thrombosis that result from hyper-coagulability. In the present study, we found that glioblastoma cells had a high level of constitutive nuclear factor (NF)-kappaB activity, which was directly correlated with necrosis in glioblastomas. We also found a direct correlation between NF-kappaB activity and the expression of tissue factor (TF), a potent procoagulant factor in gliomas. Inhibition of TF by an inhibitory antibody prevented the procoagulant activity of glioblastoma cells, indicating a TF-dependent mechanism. Blockade of NF-kappaB activation significantly inhibited TF expression and the procoagulant activity of glioblastoma cells in vitro. Blockade of NF-kappaB activation also significantly inhibited in vivo expression of TF, which was directly correlated with decreased necrosis formation and tumor growth of glioblastoma cells in nude mice. Collectively, these results suggest that elevated NF-kappaB activity in glioblastomas cells plays a critical role in necrosis formation of glioblastoma and that inhibition of NF-kappaB activity in glioblastoma can suppress necrosis formation and progressive growth.