Hideki Origasa

Toyama University, Тояма, Toyama, Japan

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Publications (99)388.14 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; 10(2). DOI:10.1111/ijs.12420 · 4.03 Impact Factor
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    ABSTRACT: Abstract OBJECTIVE: A modified World Federation of Neurosurgical Societies scale (m-WFNS scale) for aneurysmal subarachnoid hemorrhage (SAH) has recently been proposed, in which patients with Glasgow Coma Scale (GCS) scores of 14 are assigned to grade II and those with GCS scores of 13 are assigned to grade III regardless of the presence of neurologic deficits. The study objective was to evaluate outcome predictability of the m-WFNS scale in a large cohort. METHODS: This is a multi-center prospective observational study conducted in Japan. A total of 1656 SAH patients were registered during the 2.5-year study period, and the outcome predictability, using the Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) scores at discharge and at 90 days after onset, was evaluated by comparing the m-WFNS with original WFNS scale. We focused on whether significant differences in these scores were present between the neighboring grades. RESULTS: In the m-WFNS scale, significant difference between any neighboring grades was observed both in the mean GOS and mRS scores at 90 days except between grades III/IV. However, differences were not significant between grades II /III and between grades III/IV in the original WFNS scale. CONCLUSIONS: SAH-induced brain injury may be substantially severer in patients with GCS 13 than those with GCS 14, which may explain why grade III patients faired significantly worse than grade II patients by the modified WFNS scale. Although further validation is necessary, the m-WFNS scale has a potential of providing neurosurgeons with simpler and more reliable prognostication of SAH patients.
    World Neurosurgery 12/2014; DOI:10.1016/j.wneu.2014.12.032 · 2.42 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) is public health concern even in Asian countries. TRK-100STP, a sustained release tablet of an orally-active prostacyclin analogue, beraprost sodium, is suggested to suppress worsening of some parameters of renal filtration function, containing in slope of 1/serum creatinine (1/SCr) vs. time in a phase II clinical trial.Methods/design: We describe the design of the phase IIb/III trial of TRK-100STP, CASSIOPEIR (CRF Asian Study with Oral PGI2 derivative for Evaluating Improvement of Renal function) conducted in approximately 160 centers in China, Hong Kong, Japan, Malaysia, Republic of Korea, Taiwan, and Thailand. A total of 750 patients (n = 250 per group) with primary glomerular disease or nephrosclerosis were planned to be enrolled. Patients were randomized into one of three treatment groups in a double-bind, placebo-controlled manner: TRK-100STP 120 mug b.i.d.; TRK-100STP 60 mug b.i.d.; or placebo. The treatment period is planned to last 2 to 4 years. The primary efficacy endpoint is the renal composite endpoint including doubling of SCr and ESRD (dialysis induction, renal transplantation, or increase in SCr to >=6.0 mg/dL).
    BMC Nephrology 09/2014; 15(1):153. DOI:10.1186/1471-2369-15-153 · 1.52 Impact Factor
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    ABSTRACT: Background:It is disputed whether the risk of cardiogenic embolism varies with type of atrial fibrillation (AF). Although several studies have found that the risk of cardiogenic embolism was similar among paroxysmal and persistent/permanent AF, a few studies have found that patients with paroxysmal AF had a lower rate of stroke and systemic embolism than those with persistent/permanent AF. In the present study, post-hoc analysis of the J-RHYTHM Registry was done to compare the risk of thromboembolic events among 3 types of non-valvular AF (NVAF).Methods and Results:A total of 7,406 NVAF patients were followed up prospectively for 2 years. At baseline, warfarin was used for 78.6%, 90.0%, and 91.8% of patients with paroxysmal, persistent, and permanent AF, respectively. There were 126 thromboembolic events during the follow-up period. The crude event rate was 2-fold higher among the patients with permanent NVAF (2.29%) than among those with paroxysmal (1.16%) or persistent (1.20%) NVAF (P=0.001). After adjusting for warfarin use and CHA2DS2-VASc score components, however, the hazard ratio for thromboembolism did not differ between paroxysmal (reference) and permanent NVAF (1.007; 95% confidence interval: 0.955-1.061).Conclusions:The crude rate of thromboembolic events was higher in permanent NVAF than in paroxysmal NVAF, but after adjusting for warfarin use and CHA2DS2-VASc score components, paroxysmal and permanent NVAF patients had similar risk of thromboembolism.
    Circulation Journal 08/2014; 78(10). DOI:10.1253/circj.CJ-14-0507 · 3.69 Impact Factor
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    ABSTRACT: Background To maximize protection against stroke with minimal bleeding, warfarin therapy in nonvalvular atrial fibrillation (NVAF) requires tight control within a narrow therapeutic range, which might depend on racial variations. Methods The J-RHYTHM Registry followed 6404 NVAF patients treated with warfarin for 2 years. Using international normalized ratios (INRs) at or closest to the embolic and intracranial hemorrhagic (ICH) events, we determined odds ratios for ischemic stroke/systemic embolism (SE) and ICH according to any given INR with a reference INR range including 2.0. Results Ischemic stroke and SE occurred in 97 of the patients and ICH occurred in 49. The estimated INR-risk relationships showed characteristics of Japanese NVAF patients. Compared to INR-risk relationships reported for Westerners, those observed in Japanese patients were virtually identical for ischemic stroke/SE and shifted leftward by approximately 0.5 INR for ICH. Conclusion This is the largest Japanese study providing fundamental data necessary to establish optimal anticoagulation intensities. Japanese NVAF patients may require narrower therapeutic ranges than Westerners.
    Journal of Cardiology 08/2014; 65(3). DOI:10.1016/j.jjcc.2014.07.013 · 2.57 Impact Factor
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    ABSTRACT: Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer (Kiklin(®) Capsules) is a non-absorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study was a multicenter, double-blind, randomized, placebo-controlled study to confirm the superiority of bixalomer to placebo for a 4-week treatment period in patients with chronic kidney disease on hemodialysis with hyperphosphatemia. Sevelamer hydrochloride (HCl), a similar non-absorbable polymer, was used as an active comparator for open-label as a reference without statistical comparison for efficacy and safety. The primary endpoint was the change in serum phosphorus level from baseline. The safety profile was also investigated. The number of subjects was 32 in the placebo group and 31 in each bixalomer group (1.5, 3.0 and 4.5 g/day), respectively. The baseline serum phosphorus level was 7.95 to 8.25 mg/dL. Bixalomer showed a significant decrease in serum phosphorus level at all doses compared with placebo, and the adjusted mean change in serum phosphorus level from the baseline to the end of treatment (at Week 4 or at the time of discontinuation) was +0.24 mg/dL in the placebo group, -0.75 mg/dL in the 1.5 g/day group, -1.32 mg/dL in the 3.0 g/day group, and -1.80 mg/dL in the 4.5 g/day group, showing a dose-dependent decrease in serum phosphorus level. The mean change in serum phosphorus level was -2.32 mg/dL in the sevelamer HCl group under the mean dose of 4.8 g/day. Major adverse events included constipation, hard feces, vomiting, etc.; however, none of the adverse events were serious or severe. Consequently, the superiority of bixalomer to placebo and its dose-dependency for treating hyperphosphatemia were confirmed (Clinical trial registration: NCT00505037).
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 06/2014; 18 Suppl 2:24-32. DOI:10.1111/1744-9987.12202 · 1.53 Impact Factor
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    ABSTRACT: Background: Recent European guidelines recommended the CHA2DS2-VASc score for thromboembolic and the HAS-BLED score for bleeding risk stratifications. We validated these scores in 7,384 Japanese patients with nonvalvular atrial fibrillation (NVAF) enrolled in the J-RHYTHM Registry. Methods and Results: Of the study cohort, 6,387 patients taking warfarin and the other 997 not taking warfarin were prospectively examined for 2 years. Thromboembolic and major bleeding risks were stratified by modified CHA2DS2-VASc (mCHA2DS2-VASc) and HAS-BLED (mHAS-BLED) scores, respectively. Of the patients with mCHA2DS2-VASc score 0, 1, and ≥2, thromboembolism occurred in 2/141 (0.7%/year), 4/233 (0.9%/year), and 24/623 (1.9%/year), respectively, in the non-warfarin group, and in 1/346 (0.1%/year, P=0.19 vs. non-warfarin), 4/912 (0.2%/year, P=0.05), and 92/5,129 (0.9%/year, P=0.0005), respectively, in the warfarin group. When female sex was excluded from the score, thromboembolism occurred in 2/180 patients (0.6%/year), 5/245 (1.0%/year), and 23/572 (1.6%/year), respectively, in the non-warfarin group, and in 1/422 (0.1%/year, P=0.20 vs. non-warfarin), 5/1,096 (0.2%/year, P=0.02), and 91/4,869 (0.9%/year, P=0.0005), respectively, in the warfarin group. Patients with mHAS-BLED scores ≥3 were at high risk for major bleeding irrespective of warfarin treatment (1.3 and 2.6%/year in the non-warfarin and warfarin groups, respectively). Conclusions: In Japanese NVAF patients, the mCHA2DS2-VASc score is useful for identifying patients at truly low risk of thromboembolism. Female sex may be excluded as a risk from the score. mHAS-BLED score ≥3 is useful for identifying patients at high risk of major bleeding.
    Circulation Journal 04/2014; 78(7). DOI:10.1253/circj.CJ-14-0144 · 3.69 Impact Factor
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    ABSTRACT: Hyperphosphatemia is a prognostic factor for morbidity and mortality in chronic kidney disease. Bixalomer is a nonabsorbable polymer that decreases serum phosphate levels by binding phosphate in the gastrointestinal tract. This study compared the efficacy and safety of bixalomer versus sevelamer hydrochloride for controlling hyperphosphatemia in hemodialysis patients. This was a multicenter, randomized open-label, non-inferiority study. The primary endpoint was serum phosphate on completion of treatment. Administration of bixalomer was started at 1.5 g/day and adjusted to a maximum of 7.5 g/day depending on the serum phosphate level. Sevelamer hydrochloride was started at 3.0 or 6.0 g/day and adjusted to a maximum of 9.0 g/day. Treatment was continued for 12 weeks. Fifty-five patients were randomized to each treatment group. After 12 weeks, the baseline adjusted mean serum phosphate level was 5.87 mg/dL in the bixalomer group and 5.55 mg/dL in the sevelamer group, with a difference of 0.31 mg/dL and 95% confidence interval (CI) of [−0.13 to 0.76]. The upper limit of the 95%CI for the difference of the mean serum phosphate level between the two groups was <1.0 mg/dL, which was the non-inferiority margin in this study. Thus, non-inferiority of bixalomer to sevelamer was confirmed. The incidence of adverse events was lower in the bixalomer group, and bixalomer did not promote acidosis. Bixalomer achieved a similar reduction of serum phosphate to sevelamer, while causing fewer adverse reactions. Consequently, the usefulness of bixalomer for treating hyperphosphatemia was confirmed.
    Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 04/2014; 18(2). DOI:10.1111/1744-9987.12068 · 1.53 Impact Factor
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    ABSTRACT: We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine, juzentaihoto (JTT), on influenza vaccination in a multicenter randomized controlled trial. In this study, the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection. In total, 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba, Gunma, and Toyama prefectures in Japan. Participants were randomly assigned to the JTT and the control groups. Blood samples were taken at 4 weeks before vaccination, at the time of vaccination, and then at 4, 8, 12, and 24 weeks after vaccination. The hemagglutination inhibition (HI) titers against A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 were then manually measured. A significant increase in HI titer against H3N2 was observed at week 8 after vaccination in the JTT group compared with the control group (P = 0.0229), and the HI titer of the JTT group significantly increased from 4 to 24 weeks (P = 0.0468), compared with the control group. In conclusion, our results indicated that JTT increased and prolonged antibody production against A/Victoria/210/2009 (H3N2), in particular, after influenza vaccination.
    Evidence-based Complementary and Alternative Medicine 11/2013; 2013:568074. DOI:10.1155/2013/568074 · 2.18 Impact Factor
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    ABSTRACT: The effects of smoking on clinical outcomes following acute stroke remain controversial. We evaluated the influence of smoking on 90-day outcomes after acute atherothrombotic stroke in 292 Japanese men extracted from the database of the Edaravone and Argatroban Stroke Therapy for Acute Ischemic Stroke randomized parallel-group trial that tested the safety and efficacy of edaravone and argatroban therapy in 814 patients in 2004-2008. Smokers were matched with non-smokers of the same age for identical age distribution in the smoker and non-smoker groups. Poor 90-day outcomes (defined as death, Barthel index<60, or modified Rankin score>3) were evaluated using a logistic regression model. Significant variables (P<0.05) in univariate analysis were further evaluated by multivariate logistic regression analysis using a forward-selection method. Body temperature, age, National Institute of Health Stroke Scale score at admission, systolic blood pressure, and smoking status were selected in the final model. Smokers had significantly increased odds of poor 90-day functional outcomes independent of other statistically significant predictor variables (adjusted odds ratio, 2.28; 95% confidence interval, 1.15-4.55; P=0.019). In Japanese men, smoking leads to poor functional outcomes at 3months after acute atherothrombotic stroke.
    Journal of the neurological sciences 09/2013; 335(1-2). DOI:10.1016/j.jns.2013.09.023 · 2.26 Impact Factor
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    ABSTRACT: Background Low-dose aspirin is widely used for the prevention of cardiovascular events. The prevalence of gastroduodenal injuries and the risk factor profile including gastroprotective drug therapy needs to be clarified in Japanese patients taking daily aspirin for cardioprotection. Methods This Management of Aspirin-induced Gastro-Intestinal Complications (MAGIC) study was conducted with a prospective nationwide, multicenter, real-world registry of Japanese patients at high-risk of cardiovascular diseases who were taking regular aspirin (75–325 mg) for 1 month or more. All patients underwent endoscopic examination for detection of gastroduodenal ulcer and mucosal erosion. The risk factor profiles including the concurrent drug therapy were compared for those patients with gastroduodenal problems and those without. Results Gastroduodenal ulcer and erosion were detected in 6.5, and 29.2 % of the 1,454 patients receiving aspirin, respectively. H. pylori infection was associated with an increased risk for ulcer: OR 1.83 (1.18–2.88 p = 0.0082). Risk of erosion was lower with enteric-coated aspirin than with buffered aspirin: odds ratio (OR) 0.47 (0.32–0.70, p = 0.0002). Patients receiving proton pump inhibitors had lower risks for both gastroduodenal ulcer and erosion: OR 0.34 (0.15–0.68, p = 0.0050) and 0.32 (0.22–0.46, p < 0.0001), respectively. However, those receiving histamine 2-receptor antagonists had reduced risks for erosion but not for ulcer: OR 0.49 (0.36–0.68, p < 0.0001). Conclusion Gastroduodenal ulcer and erosion are common in Japanese patients taking low dose aspirin for cardioprotection. Proton pump inhibitors reduce the risk of gastroduodenal mucosal injury.
    Journal of Gastroenterology 06/2013; 49(5). DOI:10.1007/s00535-013-0839-5 · 4.02 Impact Factor
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    ABSTRACT: Background: Target anticoagulation levels for warfarin in Japanese patients with non-valvular atrial fibrillation (NVAF) are unclear. Methods and Results: Of 7,527 patients with NVAF, 1,002 did not receive warfarin (non-warfarin group), and the remaining patients receiving warfarin were divided into 5 groups based on their baseline international normalized ratio (INR) of prothrombin time (≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0). Patients were followed-up prospectively for 2 years. Primary endpoints were thromboembolic events (cerebral infarction, transient ischemic attack, and systemic embolism), and major hemorrhage requiring hospital admission. During the follow-up period, thromboembolic events occurred in 3.0% of non-warfarin group, but at lower frequencies in the warfarin groups (2.0, 1.3, 1.5, 0.6, and 1.8%/2 years for INR values of ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0059). Major hemorrhage occurred more frequently in warfarin groups (1.5, 1.8, 2.4, 3.3, and 4.1% for INR values ≤1.59, 1.6-1.99, 2.0-2.59, 2.6-2.99, and ≥3.0, respectively; P=0.0041) than in non-warfarin group (0.8%/2 years). These trends were maintained when the analyses were confined to patients aged ≥70 years. Conclusions: An INR of 1.6-2.6 is safe and effective at preventing thromboembolic events in patients with NVAF, particularly patients aged ≥70 years. An INR of 2.6-2.99 is also effective, but associated with a slightly increased risk in major hemorrhage. (UMIN Clinical Trials Registry UMIN000001569).
    Circulation Journal 05/2013; 77(9). DOI:10.1253/circj.CJ-13-0290 · 3.69 Impact Factor
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    ABSTRACT: Background: Japanese patients have been at low risk for cardiovascular events compared with Western countries, but the data regarding current treatment status and rate of subsequent atherothrombotic events after acute coronary syndrome (ACS) are limited in Japanese patients. The objective of this study was to clarify the treatment status and long-term outcomes in Japanese ACS patients. Methods and Results: The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary attack (PACIFIC) registry is a multicenter, prospective observational study of Japanese ACS patients. Consecutive patients aged ≥20 years hospitalized for ACS were enrolled from 96 hospitals and followed up for 2 years (n=3,597). ST-segment elevation myocardial infarction (STEMI) was the most frequent type of ACS (59.4%). The vast majority (93.5%) of patients underwent percutaneous coronary intervention (PCI), with a success rate of 93.9%. Frequent use of guideline-recommended pharmacological treatments was also indicated. Cumulative incidence of major adverse cardiac and cerebrovascular events (MACCE) was 6.4% (7.5% for STEMI and 4.8% for non-STEMI or unstable angina), and all-cause mortality was 6.3%. Conclusions: The PACIFIC registry has identified an incidence of MACCE of 6.4% and that of mortality at 6.3% in Japanese ACS patients at 2-year follow-up. A high proportion of patients underwent PCI, and the PCI success rate was high. Proactively performed successful PCI was considered to have contributed to favorable outcomes in these patients.
    Circulation Journal 03/2013; DOI:10.1253/circj.CJ-13-0174 · 3.69 Impact Factor
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    ABSTRACT: BACKGROUND: Although statin therapy is beneficial for preventing first strokes, the benefit for recurrent stroke and its sub-types remains unknown in Asian populations. The aim of this study is to examine the role of pravastatin in the secondary prevention of stroke in Japanese patients. METHODS: This is a multicenter, randomized, open-label, parallel group study of patients with noncardioembolic ischemic stroke (atherothrombotic infarction, lacunar infarction, and infarction of undetermined etiology). All patients were diagnosed with hyperlipidemia and with a total cholesterol level between 180 and 240 mg/dl at enrollment. Patients in the treatment group receive 10 mg/day of pravastatin, and those in the control group receive no statin treatment. The primary end-point is the recurrence of stroke, including transient ischemic attack. The secondary end-points include the onset of respective stroke sub-types and functional outcomes related to stroke. The patients were enrolled for five-years and will be followed up for five-years. RESULTS: A total of 1578 eligible patients (age: 66·2 years, men: 68·8%), including 64·2% with lacunar infarction, 25·4% with atherothrombotic infarction, and 10·4% with infarction of undetermined etiology were included in this study. Lipid levels were generally well controlled (total cholesterol: 210·0 mg/dl, low density lipoprotein cholesterol: 129·5 mg/dl) at baseline. In addition, the disability of patients was relatively mild, and cognitive function was preserved in the majority of patients. CONCLUSION: This article reports the rationale, design, and baseline features of a randomized controlled trial to assess the effects of statin for the secondary prevention of stroke. Follow-ups of patients are in progress and will end in 2014.
    International Journal of Stroke 01/2013; DOI:10.1111/ijs.12099 · 4.03 Impact Factor
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    ABSTRACT: Treatment guidelines for atrial fibrillation (AF) used in Western countries describe female gender as a risk factor for thromboembolic events in patients with non-valvular AF (NVAF). The present study aimed to determine impact of gender on prognosis of Japanese NVAF patients. A sub-analysis of 7,406 NVAF patients (mean age, 70 years) who were followed-up prospectively for 2 years was performed using data from the J-RHYTHM registry. The primary endpoints were thromboembolic events, major hemorrhaging, total mortality, and cardiovascular mortality. Compared with male subjects (n = 5,241), females (n = 2,165) were older and displayed higher prevalences of paroxysmal AF, heart failure, and hypertension, but lower prevalences of diabetes, prior cerebral infarction, and coronary artery disease. Male and female patients had mean CHADS2 scores of 1.6 and 1.8, respectively (p <0.001). Warfarin was given to 87% of male patients and 86% of female patients (p = 0.760), and the two genders displayed similar mean international normalized ratio of prothrombin time values at baseline (1.91 vs 1.90, p = 0.756). Multivariate logistic regression analysis indicated that male gender was an independent risk factor for major hemorrhaging (odds ratio, 1.59; 95% confidence interval, 1.05–2.40; p = 0.027) and all-cause mortality (1.78, 1.25–2.55, p <0.002), but not for thromboembolic events (1.24, 0.83–1.86, p = 0.297) or cardiovascular mortality (0.96, 0.56–1.66, p = 0.893). In conclusion, female gender is not a risk factor for thromboembolic events among Japanese NVAF patients that were treated mostly with warfarin. However, male gender is a risk factor for major hemorrhaging and all-cause mortality.
    The American journal of cardiology 01/2013; 113(6). DOI:10.1016/j.amjcard.2013.11.057 · 3.43 Impact Factor
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    ABSTRACT: Background: Currently, there are only a few risk scores to predict long-term recurrence of ischemic stroke and no risk score has been developed for the Asian population. The aim of the present study was to develop a new risk score to predict 1-year recurrence in Japanese patients with ischemic stroke and compare it with the other ones. Methods: Data used in this analysis were extracted from the Fukuoka stroke registry (FSR) database, including 3,067 Japanese patients who experienced ischemic stroke. FSR is a multicenter, hospital-based, prospective registry of Japanese patients with acute stroke. Associations between potential clinical variables that could be involved in the increase of risk and recurrence of ischemic stroke within 1 year after initial stroke onset were evaluated using univariate and multivariate analyses. To calculate risk scores, weighted points proportionally based on standardized coefficient values were assigned to variables that were identified to be significant risks for recurrence by multivariate analysis. The Hosmer-Lemeshow goodness-of-fit test was used to test agreement between a predicted outcome using a model and an actual observed outcome. Kaplan-Meier analysis was used to estimate average cumulative recurrence rates within three risk groups. Intergroup comparisons in recurrence rate among the risk groups were performed using a log-rank test. Results: Univariate and multivariate analyses identified nine significant predictors for 1-year recurrence, to which we assigned the following points: age (65-74 years, 1 point; ≥75 years, 2 points), hypertension (1 point), diabetes mellitus (1 point), smoker (1 point), atrial fibrillation (1 point), cardiac diseases (1 point), chronic kidney disease (1 point), nonlacunar stroke (1 point), and previous ischemic stroke (2 points). The Hosmer-Lemeshow goodness-of-fit test demonstrated good agreement between the observed and predicted recurrence rate (χ(2) = 2.30, p = 0.97). The ROC curve for the risk score models showed acceptable discriminant power with a C-statistic of 0.636 (95% confidence interval: 0.573-0.698). Trends toward increased risk of recurrence with higher scores were observed. The 1-year recurrence rates were 2.93, 5.83 and 7.96% in low- (≤3 points), intermediate (4-5 points), and high-risk groups (≥6 points), respectively. Kaplan-Meier curves with log-rank test showed a significant difference in recurrence among the three risk groups (p < 0.0001). Conclusions: A new risk score was developed and successfully validated. Our results suggest that this simple risk score enables clinicians to assess 1-year recurrence risk in Japanese patients with ischemic stroke.
    Cerebrovascular Diseases 11/2012; 34(5-6):351-357. DOI:10.1159/000343503 · 3.70 Impact Factor
  • Yukito Shinohara, Hideki Origasa
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    ABSTRACT: Angiotensin-converting enzyme inhibitors (ACEIs) are reported to reduce the incidence of aspiration pneumonia in hypertensive patients. In this study, a metaanalysis was conducted to obtain statistically more reliable estimates of outcome. The MEDLINE and JMEDICINE databases were searched and the following study selection criteria were applied: (1) comparative controlled studies identified with the following keywords: drug therapy, ACEI, hypertension, swallowing function, dysphagia, stroke, and pneumonia; (2) a minimum follow-up period of 6 months; and (3) a minimum number of patients of more than 100. Patients with hypertension and a history of stroke or transient ischemic attack (TIA) in five controlled studies that reported the incidence of pneumonia were included in the analysis. A total of 8,693 post-stroke patients were given ACEIs with another antihypertensive agent or placebo as a control. In all studies, ACEIs, particularly imidapril, exhibited preventive effects equating to a relative risk that ranged from 0.32 to 0.81 compared with controls. In the combined studies the overall relative risk of ACEI-treated patients versus controls was 0.61 (95% confidence intervals [CI] 0.51-0.75; P < 0.001). Among Asian patients, the relative risk was 0.42 (95% CI 0.32-0.56; P < 0.001). Among Japanese patients, an even greater preventive effect was found for ACEIs versus other antihypertensives (relative risk: 0.38 [95% CI 0.27-0.54; P < 0.001]). ACEIs appear to be more effective than other antihypertensive agents or placebo in reducing pneumonia risk in post-stroke patients, especially in Asian populations.
    Advances in Therapy 09/2012; 29(10):900-12. DOI:10.1007/s12325-012-0049-1 · 2.44 Impact Factor
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    ABSTRACT: BACKGROUND: The Essen stroke risk score is widely applied to predict the risk of recurrent ischemic stroke. We developed a modified Essen stroke risk score and validated it using a large prospective Effective Vascular Event REduction after STroke (EVEREST) registry including 3588 patients with ischemic stroke in Japan. Patients with cardioembolic stroke were excluded, and follow-up was one-year. METHODS: The modified Essen stroke risk score was calculated from scores for waist circumference, stroke subtype by etiology, and gender in addition to age, hypertension, diabetes mellitus, previous myocardial infarction, other cardiovascular diseases except myocardial infarction and atrial fibrillation, peripheral artery disease, smoking, and previous stroke or transient ischemic attack. A multiple logistic regression model identified the predictors (each assigned one or two points) and provided c-statistics for the modified Essen stroke risk score. We considered two outcomes, recurrent ischemic stroke and cardiovascular events (defined as the combined outcomes of fatal or nonfatal stroke, myocardial infarction, nonfatal unstable angina, and cardiac death). RESULTS: Recurrent ischemic stroke occurred in 121 patients (3·7%) and cardiovascular events occurred in 133 (4·0%) within a year. The c-statistic (used for discrimination) was 0·632 for recurrent stroke and 0·640 for cardiovascular events. Patients scoring 6 or greater were classified as high risk, otherwise were classified as low risk. Kaplan-Meier analysis revealed that the modified risk score was more predictive than the Essen stroke risk score in both men and women. CONCLUSIONS: The modified Essen stroke risk score increased the ability of the Essen stroke risk score to predict recurrent cardiovascular events. Patients with a high modified Essen stroke risk score should be candidates for intensified secondary prevention strategies.
    International Journal of Stroke 07/2012; 8(4). DOI:10.1111/j.1747-4949.2012.00841.x · 4.03 Impact Factor
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    ABSTRACT: The Japan EPA Lipid Intervention Study (JELIS) reported a 19% reduction of the risk for coronary artery disease after long-term use of pure eicosapentaenoic acid (EPA) in Japanese patients with hypercholesterolemia. The variation in plasma fatty acid composition influenced the risk of coronary events. The aim of this study was to examine in JELIS participants the possible correlation of changes in plasma fatty acids with those of serum lipids. The coefficient for the correlation between the absolute change in plasma fatty acid concentrations and the changes in serum lipids was calculated in 13,901 JELIS participants. Low-density lipoprotein (LDL) cholesterol exhibited a positive correlation with docosahexaenoic acid (DHA; r=0.117 in control group, r=0.155 in EPA group) and linoleic acid (r=0.139 in control group, r=0.177 in EPA group), but the correlation coefficients with EPA (r=0.097 in control group, r=-0.032 in EPA group) were less than 0.1. We distributed the patients into 9 groups according to tertiles of the change in EPA and DHA. The average absolute decrease of LDL cholesterol and L/H ratio in each group was significantly smaller (p<0.001) in the DHA-high tertile, but not in any EPA tertile. The changes in DHA, but not in EPA, showed a positive correlation with the changes in LDL-cholesterol.
    Journal of atherosclerosis and thrombosis 05/2012; 19(7):673-9. DOI:10.5551/jat.11593 · 2.77 Impact Factor
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    ABSTRACT: BACKGROUND: Various factors that have been implicated in recovery after the acute phase of stroke have not been well evaluated. Methods: To identify prognostic factors affecting outcomes at 90 days after stroke from the viewpoint of recovery patterns, we enrolled 660 patients from the Edaravone and Argatroban Stroke Therapy for Acute Ischemic Stroke study database. Fourteen groups of patients were identified based on an analysis of their recovery patterns according to changes in their National Institutes of Health Stroke Scale scores during the first 21 days. These groups were then divided into 2 groups: favorable recovery trend (patterns 1-3; n = 486) and poor recovery trend (patterns 4-14; n = 174). Patterns with >80% of the patients experiencing a favorable outcome (National Institutes of Health Stroke Scale score of ≤4 at 90 days) were defined as the favorable recovery trend group, whereas patterns that included ≤80% favorable outcomes were defined as the poor recovery trend group. Results: Using the poor recovery trend group, logistic regression analysis found that after controlling for covariates, lower scores at admission, fewer ischemic lesions, and nonsmoking were significant prognostic factors for a favorable outcome at 90 days. Conclusions: Based on a detailed analysis of the relationship between recovery patterns after stroke and clinical outcomes in the chronic stage of stroke, smoking cessation may improve the prognosis of patients after stroke.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 05/2012; DOI:10.1016/j.jstrokecerebrovasdis.2012.04.010 · 1.99 Impact Factor

Publication Stats

2k Citations
388.14 Total Impact Points

Institutions

  • 2007–2014
    • Toyama University
      Тояма, Toyama, Japan
    • University of Toyama
      • • Graduate School of Medicine and Pharmaceutical Science for Education
      • • Department of Internal Medicine 3
      • • Department of Pediatrics
      • • Faculty of Medicine
      Тояма, Toyama, Japan
    • Saito Yukoukai Hospital
      Ōsaka, Ōsaka, Japan
  • 2009
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
    • Yamaguchi University
      • Department of Clinical Neuroscience
      Yamaguti, Yamaguchi, Japan
  • 2002–2006
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan
  • 2002–2005
    • Kanazawa University
      • • Department of Internal Medicine
      • • School of Medicine
      Kanazawa, Ishikawa, Japan
  • 2004
    • Kyoto University
      • Department of Cardiovascular Medicine
      Kyoto, Kyoto-fu, Japan
  • 2003
    • Osaka Police Hospital
      Ōsaka, Ōsaka, Japan