Takenori Yamaguchi

Shiga University of Medical Science, Ōtu, Shiga, Japan

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Publications (72)217.78 Total impact

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    ABSTRACT: Monotherapy with antiplatelet agents is only modestly effective in secondary prevention of ischemic stroke (IS), particularly in patients with multiple risk factors such as cervicocephalic arterial stenosis, diabetes, and hypertension. While dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduced IS recurrence, particularly in the early stages after IS, it increased the risk of bleeding. Compared with aspirin, cilostazol prevented IS recurrence without increasing the incidence of serious bleeds. In patients with intracranial arterial stenosis, no significant increase in bleeding events was observed for DAPT with cilostazol and aspirin, compared to that for aspirin monotherapy. DAPT involving cilostazol may therefore be safer than conventional DAPT. These findings prompted us to conduct the Cilostazol Stroke Prevention Study for Antiplatelet Combination (CSPS.com; ClinicalTrials.gov identifier: NCT01995370) to evaluate the safety and efficacy of DAPT involving cilostazol for secondary IS prevention, in comparison with that of antiplatelet monotherapy. The CSPS.com is a multicenter, randomized, open-label, parallel-group trial. A total of 4000 high-risk patients with noncardioembolic IS will be randomized 8-180 days after onset to receive aspirin or clopidogrel monotherapy, or DAPT with cilostazol and aspirin or clopidogrel for at least one-year. The primary outcome is IS recurrence. Secondary outcomes are composite occurrences of any stroke, death from any cause, myocardial infarction, vascular death, and other vascular events. The CSPS.com is expected to provide evidence indicating whether secondary IS prevention in high-risk patients can be improved by using DAPT involving cilostazol. © 2014 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.
    International Journal of Stroke 12/2014; · 4.03 Impact Factor
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    ABSTRACT: Background: The Cilostazol Stroke Prevention Study 2 (CSPS 2) showed that cilostazol significantly reduced the risk of stroke by 25.7% relative to aspirin, with significantly fewer hemorrhagic events, in patients with prior ischemic stroke, excluding cardioembolic stroke. However, whether the benefit of cilostazol is sustained in patients with a high risk of bleeding has not been examined. Methods: We conducted a subanalysis of CSPS 2 to examine whether known risk factors for hemorrhagic stroke, such as stroke subtype and systolic blood pressure (SBP), influence the efficacy of the study drugs on hemorrhagic stroke. The relative risk reduction of hemorrhagic stroke was determined from the incidences calculated by the person-year method. The cumulative incidence rates of ischemic stroke and hemorrhagic stroke were estimated and plotted using the Kaplan-Meier method. Incidences of serious hemorrhage and hemorrhage requiring hospital admission were also evaluated in the two treatment groups. Hazard ratios (HR) and 95% confidence intervals (95% CI) calculated by the Cox proportion hazard model for cilostazol versus aspirin were assessed, and a log-rank test was used for the comparison between treatments. Results: The incidence of hemorrhagic stroke was significantly lower in the cilostazol group than in the aspirin group among patients with prior lacunar stroke (0.36 vs. 1.20% in person-year, HR 0.35, 95% CI 0.18-0.70, p < 0.01), but not among those with prior atherothrombotic stroke (0.31 vs. 0.59% in person-year, HR 0.53, 95% CI 0.14-2.0, p = 0.34). The incidence of hemorrhagic stroke was significantly lower in the cilostazol group than in the aspirin group throughout all SBP categories (Poisson regression model including time-dependent covariates, p < 0.01) including SBP above 140 mm Hg (cilostazol 0.45% vs. aspirin 1.44% in person-year; Poisson regression model including time-dependent covariates, p = 0.02). Cilostazol, compared with aspirin, significantly reduced the incidence of cerebral hemorrhage (HR 0.36, 95% CI 0.19-0.70, p < 0.01), overall hemorrhage requiring hospital admission (HR 0.53, 95% CI 0.29-0.97, p = 0.04), and gastrointestinal (GI) bleeding requiring hospital admission (HR 0.44, 95% CI 0.21-0.90, p = 0.03). Conclusions: Hemorrhagic stroke was less frequent in the cilostazol group than in the aspirin group among patients with lacunar stroke as well as those with increased blood pressure levels. As for extracranial hemorrhage requiring hospitalization, GI bleeding was also less frequent in the cilostazol than in the aspirin group. Cilostazol is supposed to be a therapeutic option to replace aspirin for secondary stroke prevention, especially in these subgroups with high risks for hemorrhagic events. © 2014 S. Karger AG, Basel.
    Cerebrovascular Diseases 05/2014; 37(4):296-303. · 2.81 Impact Factor
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    ABSTRACT: To assess the effects of intensive and moderate public education on knowledge of early stroke symptoms among a general Japanese population. Information on early stroke symptoms was distributed by leaflet 12× and by booklet twice in an intensive intervention area >22 months, and by leaflet and booklet once each in a moderate intervention area. No distribution occurred in the control area. Before and after the intervention, a mailed survey was conducted in the 3 areas. A total of 2734 individuals, aged 40 to 74 years, who did not select all 5 correct symptoms of stroke in the preintervention survey were eligible for our analysis. The numbers of correct answers selected about stroke symptoms did not differ significantly among the 3 areas in the preintervention survey (P=0.156). In the postintervention survey, the proportions of participants who selected sudden 1-sided numbness or weakness (94.2% in the intensive intervention area, 88.3% in the moderate intervention area, and 89.2% in the control area; P<0.001) and sudden severe headache (76.8%, 70.1%, and 70.4%, respectively; P<0.001) differed significantly among the 3 areas. After adjustment for confounding factors, the multivariable-adjusted odds ratios (95% confidence intervals) for correctly choosing all 5 symptoms were 1.35 (1.07-1.71) in the intensive intervention area and 0.96 (0.74-1.24) in the moderate intervention area compared with the control area. Our findings suggest that frequent distribution of leaflets and booklets significantly improved the short-term knowledge of community residents about early symptoms of stroke.
    Stroke 07/2013; · 6.16 Impact Factor
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    ABSTRACT: In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 05/2013;
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    ABSTRACT: Background: It is important that the general population be aware of the early symptoms, since it has been shown that early arrival to hospitals leads better prognosis of stroke patients. However, the general population is not well informed about the early symptoms of stroke. This study was conducted to clarify which stroke symptoms are less well known and which information sources are related to awareness of stroke symptoms. Methods: A multiple-choice, mail-in survey involving 5,540 randomly selected residents, aged 40-74 years, of 3 cities in Japan was conducted. Their knowledge about stroke symptoms and their information sources were surveyed; information sources were classified as mass media (television/newspaper/radio) and personal communication sources (posters/leaflets/internet/health professionals/family and/or friends). 'Awareness' was defined as selecting all 5 of the correct stroke symptoms from among 10 listed symptoms with decoy choices. The estimated fraction of the possible impact due to each source on the whole population was also calculated by odds ratios (ORs) and the proportion of respondents who selected each source (Pe). The combined effects of mass media and personal communication sources on awareness were also assessed. Results: Of the 5,540 residents, only 23% selected all 5 correct symptoms. Visual disturbance was the least known of the 5 symptoms (35%). All sources were positively related to awareness, with ORs (Pe) of: television, 1.58 (72.5%); newspaper, 1.79 (48.0%); radio, 1.74 (13.3%); posters, 1.73 (7.6%); leaflets, 1.50 (24.7%); Internet, 1.66 (5.6%); health professionals, 1.33 (34.8%), and family/friends, 1.21 (44.6%). The estimated fraction of the possible impact due to each source was higher for mass media (television, 0.31 and newspaper, 0.28) than personal communication sources (Internet, 0.04 and leaflets, 0.12). Mass media only and mass media/personal communication sources were significantly associated (ORs: 1.66, 2.75, respectively). Conclusions: As a single method of public education, television could be the most effective strategy. Moreover, the combined approach involving mass media and personal communication sources might have a synergistic effect. Less well-known symptoms, such as visual disturbances, should be noted in public education campaigns.
    Cerebrovascular Diseases 03/2013; 35(3):241-249. · 2.81 Impact Factor
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    ABSTRACT: Edoxaban is a once-daily (QD) oral, direct factor Xa inhibitor in clinical development for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to evaluate the safety of edoxaban in Japanese patients with NVAF. A total of 536 NVAF patients (CHADS2 ≥1) were randomized to receive double-blinded edoxaban 30, 45, or 60 mg QD or open-label warfarin (international normalized ratio [INR] 2.0-3.0 for age <70 years; 1.6-2.6 for age ≥70 years) for 12 weeks. The primary endpoint was the incidence of all bleeding events (major, clinically relevant non-major, and minor bleeds). Patients underwent CT and/or MRI to assess asymptomatic intracranial hemorrhage (ICH). Secondary endpoints included thromboembolic events and pharmacodynamic indices. The mean incidence of all bleeding events for edoxaban 30, 45, and 60mg, and warfarin was 18.5%, 22.4%, 27.7%, and 20.0%, respectively. There were no statistically significant differences among the edoxaban groups and no significant differences from the warfarin group. There were no asymptomatic ICH events in any group. One episode of cerebral infarction was observed in the edoxaban 45-mg group. Subgroup analysis suggested low body weight (≤60kg) was associated with higher bleeding risk. Edoxaban 30, 45, and 60mg QD in patients with NVAF was associated with a numerical increase in all bleeding across the dose range, but this was not statistically significant, nor was any dose compared with warfarin.
    Circulation Journal 05/2012; 76(8):1840-7. · 3.58 Impact Factor
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    ABSTRACT: A recent large, randomized trial suggested that statins may increase the risk of intracerebral hemorrhage. Accordingly, we systematically reviewed the association of statins with intracerebral hemorrhage in randomized and observational data. We screened 17 electronic bibliographic databases to identify eligible studies and consulted with experts in the field. We used DerSimonian-Laird random-effects models to compute summary risk ratios with 95% confidence intervals. Randomized trials, cohort studies, and case-control studies were analyzed separately. Only adjusted risk estimates were used for pooling observational data. We included published and unpublished data from 23 randomized trials and 19 observational studies. The complete data set comprised 248 391 patients and 14 784 intracerebral hemorrhages. Statins were not associated with an increased risk of intracerebral hemorrhage in randomized trials (risk ratio, 1.10; 95% confidence interval, 0.86-1.41), cohort studies (risk ratio, 0.94; 95% confidence interval, 0.81-1.10), or case-control studies (risk ratio, 0.60; 95% confidence interval, 0.41-0.88). Substantial statistical heterogeneity was evident for the case-control studies (I(2)=66%, P=0.01), but not for the cohort studies (I(2)=0%, P=0.48) or randomized trials (I(2)=30%, P=0.09). Sensitivity analyses by study design features, patient characteristics, or magnitude of cholesterol lowering did not materially alter the results. We found no evidence that statins were associated with intracerebral hemorrhage; if such a risk is present, its absolute magnitude is likely to be small and outweighed by the other cardiovascular benefits of these drugs.
    Circulation 11/2011; 124(20):2233-42. · 15.20 Impact Factor
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    ABSTRACT: An educational campaign by mass media has been associated with great increases in the knowledge about early symptoms of stroke. However, few studies were conducted with a controlled community intervention study. To clarify the effects of a 1-year television campaign for the whole population on improvement of knowledge about stroke symptoms in 2 cities, a campaign area and a control area in Japan were selected. Before and after the campaign, 1960 randomly selected residents aged 40 to 74 years answered a telephone survey regarding knowledge of early stroke symptoms. We calculated the percentage and 95% CIs of participants who correctly chose all 5 early symptoms of stroke in each area and in each year. Before the campaign, 53% of participants (95% CI, 50%-55%) in the campaign area and 46% (95% CI, 44%-49%) in the control area correctly chose 5 early symptoms. After the 1-year television campaign, knowledge was significantly improved only in the campaign area (campaign area, 63%; 95% CI, 60%-66%; control area, 51%; 95% CI, 48%-54%). After sex stratification, only women showed improved knowledge of early symptoms. The audience rate for the campaign television programs was found to be higher in women than in men. A 1-year stroke educational television campaign effectively improved knowledge about early stroke symptoms among Japanese women aged 40 to 74 years. No impact was found among men in this age group. Future studies should examine the impact of this approach on stroke knowledge among younger individuals and whether there are any behavioral changes that contribute to earlier presentation for treatment.
    Stroke 11/2011; 43(2):545-9. · 6.16 Impact Factor
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    ABSTRACT: The aim of the present study was to identify factors associated with functional outcome, mortality, and symptomatic intracranial hemorrhage (sICH) in patients from the Japan Alteplase Clinical Trial (J-ACT) data set with ischemic stroke treated with intravenous (IV) 0.6 mg/kg alteplase within 3 hours after onset. The patient sample comprised 103 patients from the J-ACT, a multicenter, single-dose, open-label cohort study conducted to verify the efficacy and safety of IV 0.6 mg/kg alteplase in treating acute hemispheric stroke. The effects of 21 patient baseline characteristics on a favorable outcome (as evaluated by modified Rankin scale [mRS] score of 0-1 after 3 months), death within 3 months, and incidence of sICH within 36 hours after the start of treatment were examined by univariate analysis and stepwise logistic regression analysis. The baseline characteristics associated with a favorable outcome in univariate analysis included age and National Institutes of Health Stroke Scale (NIHSS) score. The factors associated with death included age and the NIHSS score. No factors were significantly associated with sICH. In stepwise logistic regression analysis, age and NIHSS score significantly predicted both favorable outcome and death. No factors significantly predicted sICH. Age and baseline NIHSS score were independent predictors for both favorable outcome and death. Although these factors are consistent with those found to be predictors in studies on IV 0.9 mg/kg alteplase, there were no factors predicting outcomes specific for IV 0.6 mg/kg alteplase.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 11/2011; 20(6):517-22.
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    ABSTRACT: Despite improvements in treatment, stroke still carries a high death toll and disability in Asia. Extended-release dipyridamole (ER-DP) plus acetylsalicylic acid (ASA) has consistently been shown to be superior over conventional platelet inhibition by ASA. ER-DP plus ASA is well established in the secondary prevention of stroke in a lot of countries including the USA and Europe. DP has an established benefit in the treatment of heart disease in Japan; however, for the prevention of stroke, the fixed-dose combination of ER-DP plus ASA has only been investigated in a small number of patients in Japan. The aim of this double-blind, randomized clinical trial was to investigate the efficacy and safety of ER-DP plus ASA versus 81 mg ASA over 1 year. The primary end point of this study was the event rate of recurrent ischemic stroke (fatal or nonfatal) using the Kaplan-Meier method and Cox regression analysis. Of the 1,294 enrolled patients, the primary end point was analyzed in 652 patients in the ER-DP plus ASA group and 639 in the ASA group. The incidence of ischemic stroke was 6.9% for ER-DP plus ASA and 5.0% for ASA with a hazard ratio of 1.47 (95% confidence interval 0.93-2.31) for the primary end point. The ASA treatment group was found to have a lower than expected yearly event rate, compared to other studies in Japanese stroke patients. Noninferiority of ER-DP plus ASA versus ASA could not be shown. The risks of major bleeding events and intracranial hemorrhage were found to be similar between the treatment arms. There were 4 deaths (0.6%) in the ER-DP plus ASA group and 10 (1.6%) in the ASA group. The results of the study are inconclusive. Noninferiority of ER-DP plus ASA versus ASA could not be established, a difference between treatments could not be shown for the primary end point. Possible reasons for this result include a small sample size, low event rates and too short a treatment duration (ClinicalTrials. gov number, NCT00311402).
    Cerebrovascular Diseases 01/2011; 31(6):601-13. · 2.81 Impact Factor
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    ABSTRACT: It remains unknown whether the effects of 0.6 mg/kg alteplase differ with occlusion site of the middle cerebral artery (MCA). We therefore evaluated the effects of 0.6 mg/kg intravenous alteplase in patients with different sites of MCA occlusion. An exploratory analysis was made of 57 patients enrolled in the Japan Alteplase Clinical Trial II (J-ACT II), originally designed to evaluate 0.6 mg/kg alteplase in Japanese patients with unilateral occlusion of the MCA (M1 or M2 portion). The residual vessel length (in mm), determined by pretreatment magnetic resonance angiography, was used to reflect the occluded site. The proportions of patients with valid recanalization (modified Mori grade 2 to 3) at 6 and 24 hours and a modified Rankin Scale (mRS) score of 0 to 1 and of 0 to 2 at 3 months were compared between the groups dichotomized according to length of the residual vessel. Multiple logistic-regression models were generated to elucidate the predictors of valid recanalization, mRS 0 to 1, and mRS 0 to 2. Receiver operating characteristics analysis revealed that 5 mm was the practical cutoff length for dichotomization. In patients with an M1 length < 5 mm (n = 12), the frequencies of valid recanalization at 6 and 24 hours (16.7% and 25.0%) were significantly lower compared with those (62.1% and 82.8%, respectively) of the 45 patients with a residual M1 length ≥ 5 mm and an M2 occlusion (P = 0.008 for 6 hours, P < 0.001 for 24 hours). The proportions of patients who achieved an mRS of 0 to 1 and an mRS of 0 to 2 were also lower for those with an M1 length < 5 mm (8.3% and 16.7%, respectively) compared with the other group (57.8% and 68.9%, respectively; P = 0.003 for mRS 0 to 1, P = 0.002 for mRS 0 to 2). In logistic-regression models, the site of MCA occlusion (< 5 mm) was a significant predictor of valid recanalization at 6 and 24 hours and of an mRS of 0 to 1 and of mRS of 0 to 2. In patients with acute MCA occlusion, a residual vessel length < 5 mm on magnetic resonance angiography can identify poor responders to 0.6 mg/kg alteplase. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412867.
    Stroke 10/2010; 41(12):2828-33. · 6.16 Impact Factor
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    ABSTRACT: The antiplatelet drug cilostazol is efficacious for prevention of stroke recurrence compared with placebo. We designed the second Cilostazol Stroke Prevention Study (CSPS 2) to establish non-inferiority of cilostazol versus aspirin for prevention of stroke, and to compare the efficacy and safety of cilostazol and aspirin in patients with non-cardioembolic ischaemic stroke. Patients aged 20-79 years who had had a cerebral infarction within the previous 26 weeks were enrolled at 278 sites in Japan and allocated to receive 100 mg cilostazol twice daily or 81 mg aspirin once daily for 1-5 years. Patients were allocated according to a computer-generated randomisation sequence by means of a dynamic balancing method using patient information obtained at registration. All patients, study personnel, investigators, and the sponsor were masked to treatment allocation. The primary endpoint was the first occurrence of stroke (cerebral infarction, cerebral haemorrhage, or subarachnoid haemorrhage). The predefined margin of non-inferiority was an upper 95% CI limit for the hazard ratio of 1·33. Analyses were by full-analysis set. This trial is registered with ClinicalTrials.gov, number NCT00234065. Between December, 2003, and October, 2006, 2757 patients were enrolled and randomly allocated to receive cilostazol (n=1379) or aspirin (n=1378), of whom 1337 on cilostazol and 1335 on aspirin were included in analyses; mean follow-up was 29 months (SD 16). The primary endpoint occurred at yearly rates of 2·76% (n=82) in the cilostazol group and 3·71% (n=119) in the aspirin group (hazard ratio 0·743, 95% CI 0·564-0·981; p=0·0357). Haemorrhagic events (cerebral haemorrhage, subarachnoid haemorrhage, or haemorrhage requiring hospital admission) occurred in fewer patients on cilostazol (0·77%, n=23) than on aspirin (1·78%, n=57; 0·458, 0·296-0·711; p=0·0004), but headache, diarrhoea, palpitation, dizziness, and tachycardia were more frequent in the cilostazol group than in the aspirin group. Cilostazol seems to be non-inferior, and might be superior, to aspirin for prevention of stroke after an ischaemic stroke, and was associated with fewer haemorrhagic events. Therefore, cilostazol could be used for prevention of stroke in patients with non-cardioembolic stroke. Otsuka Pharmaceutical.
    The Lancet Neurology 10/2010; 9(10):959-68. · 23.92 Impact Factor
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    ABSTRACT: We examined the knowledge regarding heavy drinking and smoking as risk factors of stroke according to drinking/smoking habits among randomly selected Japanese general population. The Japan Stroke Association and co-researchers have performed a large-scale educational intervention to improve knowledge concerning stroke from 2006 to 2008. Prior to above-mentioned intervention, we conducted mail-surveillance on knowledge about stroke in 11,306 randomly selected residents aged 40 to 74. We assessed the relationship between drinking/smoking habits and knowledge regarding heavy drinking and smoking as risk factors by using the chi-square test and multiple logistic regression analysis adjusting for age, sex, area, employment, living situation, history of stroke and other stroke related diseases, history of liver disease, family history of stroke and drinking (non-drinker / ex-drinker / occasional drinker / habitual drinker) / smoking habits (non-smoker / ex-smoker / current smoker). Total 5,540 subjects (49.0%) participated in this study. Ex-smokers and current smokers had better knowledge regarding smoking as a risk factor of stroke than non-smokers (odds ratio and 95% confidence intervals: 1.89, 1.55-2.31, 1.76, 1.45-2.12, respectively). There was no difference between habitual drinkers and non-drinkers in their knowledge, whereas current smokers had greater knowledge regarding smoking than nonsmokers. Accordingly, it is suggested that it will be necessary for habitual drinkers to be enlightened regarding heavy drinking as a risk factor of stroke and for current smokers to be provided with information regarding not only these risks but also the specific strategies for invoking behavioral changes.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 10/2010; 45(5):411-9.
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    ABSTRACT: In Japan, alteplase at 0.6 mg/kg was approved in October 2005 for use within 3 hours of stroke onset by the Ministry of Health, Labor and Welfare (MHLW). The aim of the Japan post-Marketing Alteplase Registration Study (J-MARS), which was requested by MHLW at the time of approval, was to assess the safety and efficacy of 0.6 mg/kg alteplase in routine clinical practice for the Japanese. A total of 7492 patients from 942 centers were enrolled in the J-MARS, an open-label, nonrandomized, observational study, from October 2005 to October 2007. Primary outcome measures were symptomatic intracranial hemorrhage (a deterioration in NIHSS score >or=4 from baseline) and favorable outcome (modified Rankin Scale score, 0-1) at 3 months after stroke onset. The proportion of patients with symptomatic intracranial hemorrhage in 7492 patients (safety analysis) was 3.5% (95% confidence interval [CI], 3.1%-3.9%) within 36 hours and 4.4% (95% CI, 3.9%-4.9%) at 3 months. The overall mortality rate was 13.1% (95% CI, 12.4%-13.9%) and the proportion of patients with fatal symptomatic intracranial hemorrhage was 0.9% (95% CI, 0.7%-1.2%). The outcomes at 3 months were available for 4944 patients and the proportion of favorable outcome (efficacy analysis) was 33.1% (95% CI, 31.8%-34.4%). The subgroup analysis in patients between 18 and 80 years with a baseline NIHSS score <25 demonstrated that favorable outcome at 3 months was 39.0% (95% CI, 37.4%-40.6%). These data suggest that 0.6 mg/kg intravenous alteplase within 3 hours of stroke onset could be safe and effective in routine clinical practice for the Japanese.
    Stroke 09/2010; 41(9):1984-9. · 6.16 Impact Factor
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    ABSTRACT: The purpose of this study was to evaluate further the efficacy of 0.6 mg/kg intravenous alteplase on vascular and clinical outcomes in patients with middle cerebral artery occlusion in a postmarketing Phase IV trial of prospective cohort study design. Alteplase was given intravenously at 0.6 mg/kg to patients with ischemic stroke within 3 hours of onset with MR angiography-documented middle cerebral artery occlusion. Vascular outcome was evaluated by MR angiography at 6 and 24 hours after symptom onset based on the modified Mori grade. The primary end points also included a favorable outcome (modified Rankin Scale 0 to 1 at 3 months after onset) and incidence of symptomatic intracranial hemorrhage within 36 hours after treatment. The impact of recanalization on clinical outcome was assessed by stepwise logistic regression analysis. Fifty-eight patients were enrolled. Recanalization was noted in 51.7% on 6-hour MR angiography and 69.0% on 24-hour MR angiography. A favorable clinical outcome was achieved in 46.6%. None had symptomatic intracranial hemorrhage. In logistic regression models, recanalization on either 6-hour or 24-hour MR angiography was an independent predictor for clinical outcome as well as the baseline National Institutes of Health Stroke Scale score. Early recanalization of an occluded middle cerebral artery can be provoked by 0.6 mg/kg intravenous alteplase and may induce a favorable clinical outcome. The rates of recanalization and favorable outcome are comparable to that previously reported with the 0.9-mg/kg dose.
    Stroke 03/2010; 41(3):461-5. · 6.16 Impact Factor
  • Nosotchu 01/2010; 32(1):1-11.
  • Yasushi Okada, Takenori Yamaguchi
    Nosotchu 01/2010; 32(6):762-769.
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    ABSTRACT: A secreted isoform of the receptor for advanced glycation end products (RAGE), soluble RAGE (sRAGE), can neutralize the adverse effects of RAGE signaling by acting as a decoy. RAGE signaling contributes to the development of diabetic microangiopathy, however few studies have addressed pivotal roles of RAGE signaling in acute stroke. We examined plasma sRAGE levels associated with clinical features in acute stroke patients. Plasma sRAGE was measured in 482 patients (318 men; mean age 71 years) admitted within three days of stroke onset. Median values of sRAGE were significantly different among stroke subtypes (p=0.001); 1010 pg/ml in atherothrombotic infarction, 933 pg/ml in lacunar, 1280pg/ml in cardioembolic infarction, 1050 pg/ml in other types of infarctions, and 943 pg/ml in primary intracerebral hemorrhage. Severe leukoaraiosis on brain MR images, high NIHSS scores on admission, cigarette smoking, and normal estimated glomerular filtration rate were significantly associated with low sRAGE levels (p<0.05). The low level of sRAGE was associated with severe leukoaraiosis, reflecting long-standing presence of hypertensive angiopathy. Kidneys play a role in the removal of sRAGE. RAGE signaling can contribute to the deterioration of neuronal damage under severe leukoaraiosis, result in a high NIHSS score on admission in acute stroke patients, especially those with smoking habits.
    Journal of the neurological sciences 10/2009; 287(1-2):41-4. · 2.32 Impact Factor
  • Shinichiro Uchiyama, Yasuo Fukuuchi, Takenori Yamaguchi
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    ABSTRACT: Two Phase III studies comparing the safety and efficacy of clopidogrel with ticlopidine as antiplatelet agents for the secondary prevention of vascular events in patients with prior stroke were performed in Japan. Both studies were randomized, double-blind, double-dummy comparative trials with the primary objective of comparing the clinical safety of treatment with either clopidogrel or ticlopidine for up to 12 months. The secondary objective was to assess the incidence of a combined efficacy endpoint of cerebral infarction, myocardial infarction, and vascular death. Patients with prior stroke were recruited during July 1996-February 1998 and September 2001-November 2003 at centers across Japan. The results of the two studies were combined in this analysis. There were 1,869 patients in the safety population (clopidogrel, 941; ticlopidine, 928). Significantly, fewer patients experienced a safety event in the clopidogrel group than in the ticlopidine group (p < 0.001; hazard ratio, 0.610; 95% confidence interval 0.529, 0.703). Almost twice as many patients in the ticlopidine group (25.6%) experienced hepatic dysfunction than in the clopidogrel group (13.4%). There were 1,862 patients evaluable for efficacy (clopidogrel, 939; ticlopidine, 923). There was no significant difference in the incidence of the combined efficacy endpoint between clopidogrel (2.6% of patients) and ticlopidine (2.5%). Clopidogrel was better tolerated than ticlopidine. There was no difference in the efficacy of the two agents with regard to the secondary prevention of vascular events in patients with prior stroke. This was the first combined analysis of direct comparison of clopidogrel with ticlopidine in the clinical setting.
    Journal of Neurology 04/2009; 256(6):888-97. · 3.58 Impact Factor
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    ABSTRACT: The aim of this study is to determine if there was an association of stroke recurrence with metabolic syndrome (MetS), defined by the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-III) report or the International Diabetes Federation (IDF), as well as with other risk factors, including albuminuria. From February 1, 2004 to February 5, 2006, 523 patients were admitted to our Stroke Care Unit within 7 days of stroke onset. After excluding 22 patients who died in hospital and 27 patients who did not provide consent, 474 survivors (M/F=313/161, median age, 71 years) were enrolled. End-point events were fatal or nonfatal stroke. Diagnosis of MetS by NCEP-III criteria was made in 33% of patients, and by IDF criteria in 26%. During follow-up (505.4 person-years), 2 patients dropped out. Forty-nine patients among 370 with ischemic stroke and 5 patients among 102 patients with brain hemorrhage had stroke recurrence, being fatal in 3. A significant predictor of recurrence was albuminuria (HR: 1.835, 95% CI: 1.005-3.350) in ischemic stroke. There were no significant predictors of stroke recurrence in patients with brain hemorrhage. In conclusion, albuminuria, but not MetS, was a significant predictor of stroke recurrence in ischemic stroke.
    Journal of the Neurological Sciences 12/2008; 277(1-2):50-3. · 2.24 Impact Factor

Publication Stats

1k Citations
217.78 Total Impact Points


  • 2010–2013
    • Shiga University of Medical Science
      Ōtu, Shiga, Japan
    • Kumamoto University
      • Department of Neurology
      Kumamoto, Kumamoto Prefecture, Japan
  • 1996–2013
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2011
    • Tohoku University
      • Division of Cognitive Neuroscience
      Sendai, Kagoshima-ken, Japan
  • 2009–2011
    • Tokyo Women's Medical University
      • Department of Neurology
      Tokyo, Tokyo-to, Japan
  • 2008
    • Japan Red Cross Fukuoka Hospital
      Hukuoka, Fukuoka, Japan