scholarly journals Efficacy of High-Dose and Low-Dose Simvastatin on Vascular Oxidative Stress and Neurological Outcomes in Patient with Acute Ischemic Stroke: A Randomized, Double-Blind, Parallel, Controlled Trial

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Nattaphol Uransilp ◽  
Pannawat Chaiyawatthanananthn ◽  
Sombat Muengtaweepongsa

Backgrounds. Stroke is the leading cause of death and long-term disability. Oxidative stress is elevated during occurrence of acute ischemic stroke (AIS). Soluble LOX-1 (sLOX-1) and NO are used as biomarkers for vascular oxidative stress that can reflect stabilization of atherosclerotic plaque. Previous study showed that simvastatin can reduce oxidative stress and LOX-1 expression. Objectives. To evaluate neurological outcomes and serum sLOX-1 and NO levels in patients with AIS treatment with low dose 10 mg/day and high dose 40 mg/day of simvastatin. Methods. 65 patients with AIS within 24 hours after onset were randomized to treatment with simvastatin 10 mg/day or 40 mg/day for 90 days. Personal data and past history of all patients were recorded at baseline. The blood chemistries were measured by standard laboratory techniques. Serum sLOX-1 and NO levels and neurological outcomes including NIHSS, mRS, and Barthel index were tested at baseline and Day 90 after simvastatin therapy. Results. Baseline characteristics were not significantly different in both groups except history of hypertension. Serum sLOX-1 and NO levels significantly reduce in both groups (sLOX-1 = 1.19±0.47 and 0.98±0.37 ng/ml; NO = 49.28±7.21 and 46.59±9.36 μmol/l) in 10 mg/day and 40 mg/day simvastatin groups, respectively. Neurological outcomes including NIHSS, mRS, and Barthel index significantly improve in both groups. However, no difference in NO level and neurological outcomes was found at 90 days after treatment as compared between low dose 10 mg/day and high dose 40 mg/day of simvastatin. Conclusion. High-dose simvastatin might be helpful to reduce serum sLOX-1. But no difference in clinical outcomes was found between high- and low-dose simvastatin. Further more intensive clinical trial is needed to confirm the appropriate dosage of simvastatin in patients with acute ischemic stroke. This trial is registered with ClinicalTrials.gov ID: NCT03402204.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Sung Hyuk Heo ◽  
Bum Joon Kim ◽  
Dae-Il Chang ◽  
Hye-Yeon Choi ◽  
Young Seo Kim ◽  
...  

Introduction: HT047 is an herbal mixture extract of the Scutellaria baicalensis and Pueraria lobata plants, which have been widely used to treat ischemic stroke in traditional Korean medicine. The aims of this trial are to investigate whether HT047 can improve neurological status, particularly motor function, in acute ischemic stroke patients, and to determine the safety and tolerance of HT047. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, phase II trial, we enrolled patients with acute ischemic stroke within the past 14 days from 8 centers in Korea. The participating patients must have a Fugl-Meyer Assessment (FMA) motor score ≤55 with arm or leg weakness, and Korean version of the National Institutes of Health Stroke Scale (K-NIHSS) score of ≥4 and ≤15. Seventy-eight participants will be randomized in a 1:1:1 ratio and given high-dose HT047 (750 mg three times a day), low-dose HT047 (500 mg three times a day), or a placebo for 12 weeks. The primary endpoint is the change in FMA motor score between baseline and week 12. The trial is registered with ClinicalTrials.gov, NCT02828540. Results: Between Aug, 2016, and Aug, 2018, we randomly assigned 78 patients to one of the three study groups, of whom 66 patients were assessed for the primary endpoint in full analysis set. The median (min, max) changes in FMA motor score of high-dose HT047 and low-dose HT047 were 24 (0, 63) and 43 (-2, 70) (placebo group=28 [0, 63], p=0.929 and p=0.705, respectively). The prevalence of favorable outcome defined as modified Rankin scale score of 0-2 were 47.6% (p=0.919) in high-dose HT047 group and 57.1% (p=0.106) in low-dose HT047 group (31.6% in placebo group). Adverse events were similar across the three study groups. Conclusions: This study is a first-in-human trial of HT047, and there were no between-group differences on the primary and secondary endpoints.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Masayuki Shiozawa ◽  
Shoichiro Sato ◽  
Sohei Yoshimura ◽  
Kyohei Fujita ◽  
Toshihiro Ide ◽  
...  

Background and Purpose: Cerebral microbleeds (CMBs) are now considered to be one of the neuroimaging markers of cerebral small vessel disease. It has been reported that CMBs are associated with age, hypertension, cognitive impairment, and use of antithrombotic drugs. We aimed at identifying factors associated with the presence of CMBs among acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) who participated in the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-NVAF study. Methods: Acute ischemic stroke/transient ischemic attack (within 7 days of onset) patients with NVAF who underwent T2*-weighted images on magnetic resonance imagings at baseline were included in the analysis. Factors associated with the presence of CMBs were assessed in univariable and multivariable logistic regression models. Results: Of 1,099 (77.6±10.0 years, 620 male) participants, 256 (23.2%) had CMBs: single CMB in 96 (8.7%), 2-4 of CMBs in 109 (9.9%), and ≥5 CMBs in 51 (4.6%). The presence of CMBs was associated with age [per 10 years, odds ratio (OR) 1.21; 95% confidence interval (CI) 1.02-1.44], past history of stroke (OR 1.52; 95% CI 1.09-2.11), and advanced cognitive impairment (OR 1.64; 95% CI 1.02-2.61) in multivariable analysis adjusted for sex, hypertension, arterial disease, ever smoking, premorbid antithrombotic medications, and estimated glomerular filtration rate. Among 514 patients (46.8% of the participants) with the data of urinary albumin, clinical albuminuria (urinary albumin ≥300 mg/gCr) and past history of stroke were identified as independent factors associated with CMBs (OR 1.91; 95% CI 1.06-3.42 and 1.67; 1.04-2.66, respectively). Conclusions: Approximately one fourth of acute ischemic stroke patients with NVAF had CMBs. Past history of stroke and clinical albuminuria were identified as independent determinants of CMBs on top of established ones. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.


2021 ◽  
Vol 8 (20) ◽  
pp. 1516-1520
Author(s):  
Rupa Gopinathan ◽  
Deepa Gopalakrishna ◽  
Saboora Beegum ◽  
Thomas Iype

BACKGROUND Disturbance of brain iron homeostasis have been linked to acute neuronal injury following cerebral ischemia. Increased body iron stores measured as serum ferritin is an acute-phase reactant involved in cellular defence against oxidative stress and it constitutes the main intracellular iron storage protein. In a healthy population, iron excess may not be a major concern; however, in persons with high oxidative stress and dyslipidaemia, iron excess may place them at greater risk. Hence this study is undertaken to find out the role of iron in acute ischemic stroke and to estimate the iron stores, measured as serum ferritin in acute ischemic stroke patients. METHODS A minimum of 180 consecutive patients above 40 years in the acute phase of ischemic stroke within 72 hours of first episode admitted to the neurology department was selected for the study. Data collection was based on Interview method by detailed questionnaire and laboratory investigations. Quantitative determination of serum ferritin was done by immunoenzymatic colorimetric method using ELISA technique. Association of risk factors like age, gender, place of residence, history of hypertension, dyslipidaemia and diabetes between cases with elevated ferritin and normal values were analysed. RESULTS In the present study incidence of stroke was more common among patients with the age group of more than 50 years and among the 180 cases, 75 % showed elevated serum ferritin levels. Association of risk factors between cases with elevated ferritin and cases with normal ferritin were studied and it shown that history of hypertension, dyslipidaemia and diabetes were statistically significant. Multiple logistic regression showed history of hypertension and dyslipidaemia that were independent predictors of elevated ferritin levels among stroke patients. CONCLUSIONS Serum Ferritin was increased in acute ischemic stroke patients. There was significant association of factors like history of hypertension, dyslipidaemia and diabetes with elevated ferritin levels. KEYWORDS Stroke, Ferritin, Oxidative Stress, Free Radicals


2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Zhang ◽  
Hui Wei ◽  
Yu Ren ◽  
Yanping Wu ◽  
Yetao Luo ◽  
...  

Background: Intravenous thrombolysis with alteplase benefits eligible patients with acute ischemic stroke. However, in some countries such as China, alteplase may be too expensive for low-income patients, and also for regions with low economic development. Urokinase is much less expensive than alteplase. This study aimed to assess the outcomes and treatment complications of urokinase in acute ischemic stroke patients, which are poorly understood.Methods: This multicenter retrospective study included acute ischemic stroke patients who received intravenous urokinase or alteplase from January 2014 to January 2018 at 21 centers in China. Outcomes and treatment complications were analyzed by univariate and multivariate analyses.Results: Among the 618 patients included in this study, 489 were treated with urokinase and 129 were treated with alteplase. Functional independence, no/minimal disability, mortality, intracranial hemorrhage (ICH), and symptomatic ICH did not significantly differ between the urokinase and alteplase groups in the univariate and multivariate analyses. However, the patients who received alteplase had a lower odds ratio (OR) of extracranial bleeding in the univariate analysis and a lower adjusted OR (aOR) in the multivariate analysis than the patients who received urokinase (OR = 0.410 [95% CI, 0.172–0.977], p = 0.038; aOR = 0.350 [95% CI, 0.144–0.854], p = 0.021). Furthermore, in patients treated with urokinase, the patients who received high-dose urokinase had a higher OR of extracranial bleeding in the univariate analysis and a higher aOR of extracranial bleeding in the multivariate analysis than patients who received low-dose urokinase (OR = 3.046 [95% CI, 1.696–5.470], p < 0.001; aOR = 3.074 [95% CI, 1.627–5.807], p = 0.001). Moreover, patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase.Conclusions: Patients treated with urokinase had similar outcomes but a higher risk of extracranial bleeding compared to patients treated with alteplase. The risk of extracranial bleeding was higher in the patients treated with high-dose urokinase than in the patients treated with low-dose urokinase. Patients who received low-dose urokinase had similar outcomes and complications compared to patients treated with alteplase. In countries such as China where some acute ischemic stroke patients cannot afford alteplase, urokinase may be a good alternative to alteplase for intravenous thrombolysis.


2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Haomeng Zhu ◽  
Ankush Chandra ◽  
Xiaokun Geng ◽  
Zhe Cheng ◽  
Yanna Tong ◽  
...  

2019 ◽  
Vol 24 (5) ◽  
pp. 558-571 ◽  
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Christopher Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.


2017 ◽  
Vol 79 (1-2) ◽  
pp. 68-73 ◽  
Author(s):  
Guangjian Zhao ◽  
Tingfen Huang ◽  
Mei Zheng ◽  
Yansen Cui ◽  
Yunyong Liu ◽  
...  

Objective: This study analyzed the efficacy and safety of low-dose and standard-dose alteplase intravenous thrombolytic therapy for acute ischemic stroke (AIS). Methods: Patients with AIS who underwent intravenous alteplase thrombolysis from July 2012 to December 2016 were retrospectively analyzed and correspondingly divided into low-dose (0.6–0.89 mg/kg) group and standard-dose group (0.9 mg/kg) according to alteplase dosage. The clinical outcome was evaluated by modified Rankin Scale (mRS) at 90 days after onset. The safety index was the mortality at 90 days after onset and the incidence of symptomatic intracranial hemorrhage (SICH) within 7 days. Results: A total of 1,486 patients were included (1,115 cases in low-dose group and 371 cases in standard-dose group). There were no significant differences in baseline data between the 2 groups. As mRS, good outcome rate as well as mortality rate in both groups had no significant difference (36.1 vs. 37.6%; χ2 = 10.882, p = 0.890; 5.5 vs. 7.3%; χ2 = 2.163, p = 0.076), but the incidence of SICH in low-dose group was significantly lower than that of the standard-dose group (2.2 vs. 5.9%; χ2 = 3.157, p = 0.001). Conclusion: The efficacy of low-dose alteplase intravenous thrombolytic therapy for AIS was equivalent to the standard-dose regimen but with higher safety.


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