Efficacy Of Edaravone Research Articles

Safety and efficacy of edaravone combined with alteplase for patients with acute ischemic stroke: A systematic review and meta-analysis.

Early administration of edaravone for acute ischemic stroke patients (AIS) receiving intravenous thrombolysis (IVT) has a potential neuroprotective effect. This study aimed to estimate the safety and efficacy of edaravone for AIS patients receiving IVT. We searched PubMed, Embase, Cochrane Library and Chinese Databases (CNKI database, Weipu database, and Wanfang database) for randomized controlled trials (RCT) from the inception of the database to 20 July 2020. Efficacy outcome was reduced National Institutes of Health Stroke Scale (NIHSS) score before and after treatment. Safety outcomes were intracranial hemorrhage (ICH) and mortality. Review Manager 5.3 and Stata 14.0 was used to perform the meta-analysis. A total of 1877 AIS patients from 17 studies were included, 939 (50.03%) patients received edaravone combined with alteplase treatment. Compared with alteplase alone, combined treatment reduced the NIHSS score (MD=3.95,95% CI 2.92-4.99, I² = 92%) and ICH (OR=0.44,95% CI 0.29-0.66, I² =0%) during hospitalization. There was no significant association between combined treatment and mortality during follow-up (OR=0.43,95% CI 0.13-1.42, I² =0%). Conclusions: Edaravone combined with alteplase seems to be safe and effective for AIS patients' short term outcomes.

Safety and efficacy of edaravone in well-defined Iranian patients with amyotrophic lateral sclerosis: A parallel-group single-blind trial

Background: This parallel-group single-blind trial evaluates the safety and efficacy of Edaravone, as a free radical scavenger, in a highly selective subgroup of Iranian patients with amyotrophic lateral sclerosis (ALS). Methods: The study was registered in ClinicalTrials.gov (registration number: NCT03272802) and Iranian Registry of Clinical Trials (registration number: IRCT20190324043105N). Patients were included into the study, who were diagnosed as probable or definite ALS (according to revised El Escorial criteria), mildly to moderately affected by the disease [according to Amyotrophic Lateral Sclerosis Health State Scale (ALS/HSS)], scored ≥ 2 points on all items of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and had forced vital capacity (FVC) of at least 80%. 20 patients (10 cases, 10 controls) were observed for 12 cycles (each cycle lasted four weeks). Cases received Edaravone for the first 14 days in the first cycle and for the first 10 days in the next cycles. In addition, all patients received Riluzole. The 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40), ALSFRS-R, and Manual Muscle Testing (MMT) scores were measured every 3 cycles to evaluate the physical and functional status of the patients. Besides, injection reactions, adverse events (AEs), and serious adverse events (SAEs) were measured during the study. Results: ALSAQ-40, ALSFRS-R, and MMT scores were not significantly different between cases and controls in 5 different time points. During the study, no injection reactions were observed. AEs and SAEs were not significantly different between cases and controls. Conclusion: Our data did not demonstrate efficacy of Edaravone in ALS treatment, but showed its safety for use in patients with ALS. Further studies are necessary to investigate Edaravone efficacy in patients with ALS before prescribing this new drug outside Japan.

P0645EDARAVONE MAY DECREASE THE INCIDENCE OF CONTRAST INDUCED ACUTE KIDNEY INJURY (CI-AKI)

Abstract Background and Aims Edaravone is a low-molecular-weight antioxidant drug targeting peroxyl radicals of reactive oxygen species and has shown clinical efficacy in patients with acute ischemic stroke. We have conducted a multicenter open prospective randomized controlled study to evaluate the efficacy of edaravone in preventing AKI in patients with CKD 3b-4 stages. Method The study included 2 groups of patients aged 46 to 68 (55 ± 3): group A (n=16) with CKD stage 3b or 4 (eGFR EPI 32 ± 4 ml/min) that received intravenous edaravone 30 mg bid on 0,1,2 day of contrast media infusion and control group B (n=20) with CKD stage 3b or 4 (eGFR EPI 33 ± 3 ml/min) with no edaravone intervention during CT coronarography. Patients of both groups received intravenous hydration with 0.9% sodium before CT. Primary endpoint: CIN onset in 48 hours after contrast media infusion and need for RRT. Secondary endpoint: serum potassium level above 5.5 mmol/l. Results CIN onset was obtained in 4 patients of group A and 12 patients of group B (p>0,05, RR 0.417, RRR 0.583, RD 0.350, NNT 2.857). Other results are presented in table

Safety and Efficacy of Edaravone in Delaying Functional Decline in Amyotrophic Lateral Sclerosis: A Meta-Analysis (P1.4-025)

Safety and Efficacy of Edaravone in Delaying Functional Decline in Amyotrophic Lateral Sclerosis: A Meta-Analysis (P1.4-025)

Early post-marketing experience with edaravone in an unselected group of patients with ALS

Introduction: Treatment with edaravone has shown efficacy in a subgroup of patients with amyotrophic lateral sclerosis (ALS). However, it has been estimated that <7% of ALS patients fulfill the stringent inclusion criteria of the trial. In the current study, we aimed to explore retrospectively the efficacy of edaravone in unselected ALS patients. Methods: Demographic and clinical data were retrospectively collected for 22 patients who opted for treatment with edaravone and 71 untreated ALS patients attending the ALS clinic at Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, between May 2017 and January 2018. Clinical data were extracted for a baseline visit at treatment onset, and for pre-baseline and post-baseline visits, roughly 6 months apart from the baseline visit. Results: Baseline demographic and clinical characteristics were similar between edaravone treated and untreated patients, except for shorter disease duration in edaravone treated patients. Muscle strength, ALS Functional rating scale (ALSFRS-R), and respiratory function were similar between edaravone treated and untreated patients, including monthly rate of decline before and after baseline visit. Among treated patients, 7 had major respiratory complications occurring between 8 days to 7 months after treatment initiation, during or within hours following infusions. Discussion: Results of our study comparing edaravone treated and untreated patients in a real-life setting showed no differences in the rate of monthly decline of ALSFRS-R, in line with previous reports in ALS patients not treated with edaravone, and a previous clinical trial. Our findings might suggest that edaravone is not effective in unselected ALS patients.

Post-hoc analysis of open-label extension period of study MCI186-19 in amyotrophic lateral sclerosis

Study MCI186-19 investigated the safety and efficacy of edaravone in the treatment of ALS. The 24-week, double-blind period was followed by a 24-week, open-label, active extension period. Patients originally receiving edaravone continued edaravone (E-E group, n = 65), and patients originally receiving placebo switched to edaravone (P-E group, n = 58). Because no statistical tests had been prospectively planned in the open-label period, we performed post-hoc analyses to assist in the interpretation of efficacy data. A mixed model for repeated measures (MMRM) and the Combined Assessment of Function and Survival (CAFS) were assessed. Additionally, slopes of time-dependent change between baseline in cycle 1 and the end of cycle 6 (24 weeks double-blind) and between the end of cycle 6 and end of cycle 12 (24 weeks open-label) were calculated using a random coefficient model including all available data during each period.At week 48, the MMRM analysis showed significantly less decline in ALS Functional Rating Scale-Revised (ALSFRS-R) total score in the E-E group than in the P-E group (least-squares mean change from baseline ± standard error, 4.17 ± 1.40, p = 0.0037), meaning that the differences in the ALSFRS-R total score during the 24-week double-blind period were maintained in patients receiving edaravone for an additional 24 weeks. The CAFS endpoint (p = 0.0089) supported this finding. The slope analysis during the double-blind period showed a significant difference between the treatment groups, while there was no significant difference between the groups during the active extension period. These analyses suggest a potential benefit of early and continued edaravone treatment over delayed edaravone treatment.

Safety and efficacy of edaravone in well defined patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled trial

In a previous phase 3 study in patients with amyotrophic lateral sclerosis (ALS), edaravone did not show a significant difference in the Revised ALS Functional Rating Scale (ALSFRS-R) score compared with placebo. Post-hoc analysis of these data revealed that patients in an early stage with definite or probable diagnosis of ALS, defined by the revised El Escorial criteria, who met a select set of inclusion criteria showed a greater magnitude of effect than did the full study population. We aimed to substantiate this post-hoc result and assess safety and efficacy of edaravone in a phase 3 trial that focused on patients with early stage ALS who met the post-hoc analysis inclusion criteria. In this phase 3, randomised, double-blind, parallel-group study, patients aged 20-75 years with ALS of grade 1 or 2 in the Japan ALS Severity Classification, scores of at least 2 points on all 12 items of ALSFRS-R, forced vital capacity of 80% or more, definite or probable ALS according to the revised El Escorial criteria, and disease duration of 2 years or less were recruited from 31 hospitals in Japan. Eligible patients also had a decrease of 1-4 points in the ALSFRS-R score during a 12-week observation period before randomisation. Patients meeting all criteria were then randomly assigned 1:1 to receive 60 mg intravenous edaravone or intravenous saline placebo for 6 cycles (4 weeks per cycle with 2 weeks on, 2 weeks off) for a total treatment duration of 24 weeks. In cycle 1, the study drug or placebo was administered once per day for 14 days within a 14 day period, followed by the drug-free period. In cycle 2 and thereafter, the study drug or placebo was administered for 10 days within a 14 day period, followed by a 2 week drug-free period. Participants and investigators, including those assessing outcomes, were masked to treatment allocation. The primary efficacy outcome was the change in ALSFRS-R score from the baseline to 24 weeks (or at discontinuation if this was after the third cycle) after randomisation. The primary outcome was assessed in all patients who had received at least one treatment infusion, had at least one assessment post-baseline, and reached the end of cycle 3. For patients with missing values at the end of cycle 6, data were imputed by the last observation carried forward (LOCF) method, provided the patients had completed at least cycle 3. Safety was assessed in all patients who had received at least one treatment infusion and had at least one assessment post-baseline. This trial is registered with ClinicalTrials.gov, NCT01492686. Between Nov 28, 2011, and Sept 3, 2014, we screened 213 patients, and enrolled 192 as potential participants. Of these, 137 patients completed the observation period: 69 were randomly assigned to receive edaravone, and 68 were randomly assigned to receive placebo. 68 patients taking edaravone and 66 taking placebo were included in the primary efficacy analysis. For the primary outcome, the change in ALSFRS-R score was -5·01 (SE 0·64) in the edavarone group and -7·50 (0·66) in the placebo group. The least-squares mean difference between groups was 2·49 (SE 0·76, 95% CI 0·99-3·98; p=0·0013) in favour of edaravone. Treatment-emergent adverse events were reported in 58 (84%) patients receiving edaravone and 57 (84%) patients receiving placebo. 11 (16%) patients taking edaravone and 16 (24%) taking placebo had serious adverse events, and one (1%) patient receiving edaravone and four (6%) patients receiving placebo had adverse events (one dysphagia in edaravone group and one dyspnoea, two respiratory disorder, and one rash in the placebo group) that led to withdrawal. Edaravone showed efficacy in a small subset of people with ALS who met criteria identified in post-hoc analysis of a previous phase 3 study, showing a significantly smaller decline of ALSFRS-R score compared with placebo. There is no indication that edaravone might be effective in a wider population of patients with ALS who do not meet the criteria. Mitsubishi Tanabe Pharma Corporation.

Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration

Objectives and methods: Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined.Results and discussion: Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < −5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

Safety and efficacy of edaravone, a free radical scavenger, in the treatment of ALS: randomized, double–blind, placebo–controlled study

Safety and efficacy of edaravone, a free radical scavenger, in the treatment of ALS: randomized, double–blind, placebo–controlled study

Efficacy, safety, and outcomes in 17 pediatric cases treated with the free radical scavenger edaravone.

Edaravone is a free radical scavenger with brain protection properties and is recommended by "The Japanese Guidelines for the Management of Stroke 2009" for administration to adult patients, in whom it has been shown to improve neurological deficits after cerebral infarction. However, its dosage and effects have not yet been established in children. Seventeen pediatric patients with cerebral ischemia were administered edaravone at a dose based on body weight from the standard dose given to adults. Functional outcomes were evaluated using mRS and PSOM (modified ranking scale and pediatric stroke outcome scale, respectively). Immediate post-treatment results were mostly positive, with no liver or renal complications. In some cases, neurological symptoms markedly improved after the administration of edaravone. The efficacy of edaravone has not yet been examined in pediatric patients. The results of the present study suggest that edaravone has potential in the treatment of children safely with promising results similar to those in adults.

Efficacy and safety of therapies for acute ischemic stroke in China: a network meta-analysis of 13289 patients from 145 randomized controlled trials.

BackgroundMany of these therapies have been compared against placebos, but have not been directly compared against each other. To evaluate the efficacy and safety of several commonly used drugs for AIS directly or indirectly.MethodsA systematic literature review was performed to identify randomized controlled trials (RCTs) published prior to April 2013 for AIS therapies. The primary outcome measures were the National Institutes of Health Stroke Scale (NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and meta-regression are performed; lastly, performed a mixed treatment comparison was performed through the Bayesian methods.ResultsOutcome of Efficacy of therapies for acute ischemic stroke are as followed: All of the therapies mentioned above yielded results a more effective result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18–4.61); Sodium ozagrel + edaravone (RR 9.60, 95%CI 7.04–13.06); Edaravone (RR 4.07, 95%CI 3.30–5.01); Edaravone + Kininogenase (RR 15.33, 95%CI 10.03–23.05). The significant difference in efficacy between edaravone monotherapy and Sodium ozagrel + edaravone was evident (RR 0.43, 95%CI 0.08–0.61) and was also significant between efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI 2.47–6.24). The differences between the risk and benefit were not significant when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological function: Placebo served a significant difference in treating the defects of neurological function compared with Sodium ozagrel (WMD = −3.11, 95%CI −4.43 to −1.79), Sodium ozagrel + edaravone (WMD = −6.25, 95%CI −7.96 to −4.54) and Edaravone + Kininogenase (WMD = −3.47, 95%CI −5.73 to −1.21).ConclusionsIt provides that the efficacy of edaravone monotherapy in treatment was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone + Kininogenase monotherapy in treatment was more effective than Sodium ozagrel. Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone + Kininogenase can improve the nerve dysfunction.

Effects of smoking on outcomes after acute atherothrombotic stroke in Japanese men

BackgroundThe effects of smoking on clinical outcomes following acute stroke remain controversial. MethodsWe 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. ResultsBody 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). ConclusionsIn Japanese men, smoking leads to poor functional outcomes at 3months after acute atherothrombotic stroke.

The efficacy of edaravone combined with vinpocetine for ac ute cerebral infarction

Objective To observe the efficacy of edaravone combined with vinpocetine in the treatment of acute cerebral infarction.Methods 60 patients were randomly assigned to receive combination therapy with edaravone and vinpocetine ( 30 patients,study group ),or vinpocetine alone ( 30 patients,control group ).Both groups also received basic treatment.Results There was a significant difference between the study group and the control group in total effectiveness rate( 100％ vs.70％,P＜ 0.05 ）, and the study group was superior to the control group in the efficacy.Conclusion Combination therapy with edaravone and vinpocetine can markedly increase the efficacy in the treatment of acute cerebral infarction.It is worth popularizing in clinical practice. Key words: Edaravone; Vinpocetine; Acute cerebral infarction; Efficacy

The efficacy of edaravone combined with ganglioside for acute cerebral infarction

Objective To explore the efficacy of edaravone combined with ganglioside for acute cerebral infarction. Methods 138 patients with acute cerebral infarction from June 2007 to June 2010 were randomly divided into study group and control group, 69 patients for each group. The control group received conventional therapy, aspirin for controlling blood platelets, control of blood pressure and sugar and water to intracranial hypotension, protection of cerebral cells, and improvement of circulation, mannitol, salvia miltiorrhiza, andciticoline; The study group on the edaravone plus ganglioside besides conventional therapy.All the patients were assessed using National Institutes of Health Stroke before and after treatment.Results21 days after therapy, the overall response rate was 82.61%in the study group and 31.88% in the control group, and the total effective rate was 94.41% and 39.13%, respectvely: there was a statistical difference between the two groups (P＜0.05). Scores for NIHSS differed significantly between the two groups (P＜0.05).Conclusions Edaravone combined with ganglioside for acute cerebral infarction is safe and effective and can increase the recovery of nerve function, protect the cerebral tissue, reduce disability rate, and improve the quality of life. Key words: Acute cerebral infarction; Edaravone; Ganglioside

Therapeutic effect of edaravone on inner ear barotrauma in the guinea pig

Inner ear barotrauma (IEB) that is caused by acute pressure changes can often lead to permanent severe sensorineural hearing loss (SNHL). However, the mechanism that causes IEB is still unknown. In the current study, we assessed the involvement of reactive oxygen species (ROS) in IEB and the therapeutic effect of 3-methyl 1-phenyl-2-pyrazolin-5-one (edaravone), which is a free radical scavenger. To create the IEB model, guinea pigs were subjected to quick pressure changes that resulted in acute SNHL. The animals were then divided into two groups, an edaravone-treated IEB group and a non-treated IEB group that only received normal saline. Immunohistochemical analyses for 8-hydroxy-2-deoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal (4-HNE) were performed to examine the amount of oxidative DNA damage and lipid peroxidation that occurred in guinea pig cochlea. To assess the curative efficacy of edaravone, auditory brainstem response (ABR) testing was performed to evaluate auditory function. Strong immunoreactivities against 8-OHdG and 4-HNE were observed in the inner ear tissues of the non-treated IEB group. Lesser amounts of immunoreactivity were observed in the same region of the edaravone-treated IEB group as compared to the non-treated IEB group. Furthermore, ABR measurement revealed that there was a faster improvement in the threshold shift for the edaravone-treated IEB group as compared to that of the non-treated IEB group. At the final 7-week time point, the threshold shift for the edaravone-treated IEB group was significantly smaller as compared to the non-treated IEB group. These results strongly suggest that ROS is produced in the cochlea in response to acute pressure changes and that ROS plays an important role in the pathophysiology of IEB. Furthermore, edaravone treatment had a therapeutic effect on IEB-induced acute SNHL and thus, edaravone might possibly be able to be used as a therapeutic treatment for IEB.

Effects of free radical scavenger on acute liver injury induced by d‐galactosamine and lipopolysaccharide in rats

Acute severe liver injury still has a high mortality rate. Acute liver injury induced by a coadministration of d-galactosamine (GalN) and lipopolysaccharide (LPS) is an experimental model of fulminant hepatitis in rats. Our aim is to investigate the effects of free radical scavenger on the injury induced by GalN/LPS in rats. Free radical scavenger edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) was twice injected into rats 5 min before and 60 min after the GalN/LPS injection. Liver injury was biochemically and histologically assessed. The survival rate was examined 72 h after the intoxication. In the GalN/LPS-treated rats, a marked elevation in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels was observed. On the other hand, edaravone significantly inhibited the elevation in serum AST and ALT levels. The efficacy of edaravone was also confirmedby histological analysis. Edaravone lowered the levels of proinflammatory cytokines TNF-alpha mRNA and interleukin-6 mRNA expression, antioxidative enzyme heme oxygenase-1 protein and myeloperoxidase activity, a marker of neutrophil infiltration, in rat livers. In addition, edaravone reduced the mortality rate in GalN/LPS-treated rats as compared to the rats without edaravone treatment. Free radical scavenger edaravone effectively ameliorated the liver injury induced by the GalN/LPS administration in rats, not only by attenuating oxidative stress, but also by reducing the expression of proinflammatory cytokines.

Efficacy of Edaravone, a Free Radical Scavenger, for the Treatment of Acute Lacunar Infarction

The effect of edaravone as an inhibitor of ischemic brain damage in addition to routine treatment was retrospectively examined in 70 patients with lacunar infarction who were admitted within 24 hours of symptom onset. Clinical status was assessed using the National Institutes of Health Stroke Scale (NIHSS). The modified Rankin Scale (MRS) was used to assess clinical outcomes at 3 months after onset, with a good outcome defined as MRS score < or =2. Risk factors were also evaluated, including evidence of hypertension, diabetes mellitus, hyperlipidemia, coronary heart disease, and a history of smoking longer than 2 months. The probability of a good outcome and independence at 3 months was assessed by backward stepwise logistic regression analysis based on the maximum likelihood ratio. Administration of edaravone yielded an odds ratio with multivariate adjustment of 6.49 (95% confidence interval, 1.35 to 50.32; p < 0.05) for a good outcome at 3 months. Higher baseline NIHSS score and higher age also adversely affected the outcome at 3 months (p < 0.005). Administration of edaravone improves the outcome of patients with lacunar infarction.

Smoke Inhalation

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 3 months after acute atherothrombotic stroke.