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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 47, No. 9 ( 2016-09), p. 2323-2330
    Abstract: In patients with acute ischemic stroke caused by large artery atherosclerosis, clopidogrel plus aspirin versus aspirin alone might be more effective to prevent recurrent cerebral ischemia. However, there is no clear evidence. Methods— In this multicenter, double-blind, placebo-controlled trial, we randomized 358 patients with acute ischemic stroke of presumed large artery atherosclerosis origin within 48 hours of onset to clopidogrel (75 mg/d without loading dose) plus aspirin (300-mg loading followed by 100 mg/d) or to aspirin alone (300-mg loading followed by 100 mg/d) for 30 days. The primary outcome was new symptomatic or asymptomatic ischemic lesion on magnetic resonance imaging within 30 days. Secondary outcomes were 30-day functional disability, clinical stroke recurrence, and composite of major vascular events. Safety outcome was any bleeding. Results— Of 358 patients enrolled, 334 (167 in each group) completed follow-up magnetic resonance imaging. The 30-day new ischemic lesion recurrence rate was comparable between the clopidogrel plus aspirin and the aspirin monotherapy groups (36.5% versus 35.9%; relative risk, 1.02; 95% confidence interval, 0.77–1.35; P =0.91). Of the recurrent ischemic lesions, 94.2% were clinically asymptomatic. There were no differences in secondary outcomes between the 2 groups. Any bleeding were more frequent in the combination group than in the aspirin monotherapy group, but the difference was not significant (16.7% versus 10.7%; P =0.11). One hemorrhagic stroke occurred in the clopidogrel plus aspirin group. Conclusions— Clopidogrel plus aspirin might not be superior to aspirin alone for preventing new ischemic lesion and clinical vascular events in patients with acute ischemic stroke caused by large artery atherosclerosis. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00814268.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 2 ( 2022-02), p. 457-462
    Abstract: Although statins are effective in secondary prevention of ischemic stroke, they are also associated with an increase risk of intracranial hemorrhage (ICH) in certain conditions. In the TST trial (Treat Stroke to Target), we prespecified an exploration of the predictors of incident ICH. Methods: Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL (low-density lipoprotein) cholesterol of 〈 70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. Results: Among 2860 patients enrolled, 31 incident ICH occurred over a median follow-up of 3 years (18 and 13 in the lower and higher target group, 3.21/1000 patient-years [95% CI, 2.38–4.04] and 2.32/1000 patient-years [95% CI, 1.61–3.03] , respectively). While there were no baseline predictors of ICH, uncontrolled hypertension (HR, 2.51 [95% CI, 1.01–6.31], P =0.041) and being on anticoagulant (HR, 2.36 [95% CI, 1.00–5.62], P =0.047)] during the trial were significant predictors. On-treatment low LDL cholesterol was not a predictor of ICH. Conclusions: Targeting an LDL cholesterol of 〈 70 mg/dL compared with 100±10 mg/dL in patients with atherosclerotic ischemic stroke nonsignificantly increased the risk of ICH. Incident ICHs were not associated with low LDL cholesterol. Uncontrolled hypertension and anticoagulant therapy were associated with ICH which has important clinical implications. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875; EUDRACT identifier: 2009-A01280-57.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 4 ( 2020-04), p. 1231-1239
    Abstract: The TST trial (Treat Stroke to Target) evaluated the benefit of targeting a LDL (low-density lipoprotein) cholesterol of 〈 70 mg/dL to reduce the risk of cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature or aortic arch plaque 〉 4 mm, in a French and Korean population. The follow-up lasted a median of 5.3 years in French patients (similar to the median follow-up time in the SPARCL trial [Stroke Prevention by Aggressive Reduction in Cholesterol Level]) and 2.0 years in Korean patients. Exposure duration to statin is a well-known driver for cardiovascular risk reduction. We report here the TST results in the French cohort. Methods— One thousand seventy-three French patients were assigned to 〈 70 mg/dL (1.8 mmol/L) and 1075 to 100±10 mg/dL (90–110 mg/dL, 2.3–2.8 mmol/L). To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe on top if needed. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. Results— After a median follow-up of 5.3 years, the achieved LDL cholesterol was 66 (1.69 mmol/L) and 96 mg/dL (2.46 mmol/L) on average, respectively. The primary end point occurred in 9.6% and 12.9% of patients, respectively (HR, 0.74 [95% CI, 0.57–0.94]; P =0.019). Cerebral infarction or urgent carotid revascularization following transient ischemic attack was reduced by 27% ( P =0.046). Cerebral infarction or intracranial hemorrhage was reduced by 28% ( P =0.023). The primary outcome or intracranial hemorrhage was reduced by 25% ( P =0.021). Intracranial hemorrhages occurred in 13 and 11 patients, respectively (HR, 1.17 [95% CI, 0.53–2.62]; P =0.70). Conclusions— After an ischemic stroke of documented atherosclerotic origin, targeting a LDL cholesterol of 〈 70 mg/dL during 5.3 years avoided 1 subsequent major vascular event in 4 (number needed to treat of 30) and no increase in intracranial hemorrhage. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 8 ( 2023-08), p. 1993-2001
    Abstract: Whether a strategy to target an LDL (low-density lipoprotein) cholesterol 〈 70 mg/dL is more effective when LDL is reduced 〉 50% from baseline rather than 〈 50% from baseline has not been investigated. METHODS: The Treat Stroke to Target trial was conducted in France and South Korea in 61 sites between March 2010 and December 2018. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned to a target LDL cholesterol of 〈 70 mg/dL or 100±10 mg/dL, using statin and/or ezetimibe as needed. We used the results of repeated LDL measurements (median, 5 [2–6] per patient) during 3.9 years (interquartile range, 2.1–6.8) of follow-up. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death. Cox regression model including lipid-lowering therapy as a time-varying variable, after adjustment for randomization strategy, age, sex, index event (stroke or transient ischemic attack), and time since the index event. RESULTS: Among 2860 patients enrolled, patients in the lower target group who had 〉 50% LDL cholesterol reduction from baseline during the trial had a higher baseline LDL cholesterol and a lower LDL cholesterol achieved as compared to patients who had 〈 50% LDL cholesterol reduction (155±32 and 62 mg/dL versus 121±34 and 74 mg/dL, respectively, P 〈 0.001 for both). In the 〈 70 mg/dL target group, patients with 〉 50% LDL reduction had a significant reduction in the primary outcome as compared to the higher target group (hazard ratio, 0.61 [95% CI, 0.43–0.88]; P =0.007) and patients with 〈 50% LDL reduction from baseline had little reduction (hazard ratio, 0.96 [95% CI, 0.73–1.26]; P =0.75). CONCLUSIONS: In this post hoc analysis of the TST trial, targeting an LDL cholesterol of 〈 70 mg/dL reduced the risk of primary outcome compared with 100±10 mg/dL provided LDL cholesterol reduction from baseline was superior to 50%, thereby suggesting that the magnitude of LDL cholesterol reduction was as important to consider as the target level to achieve. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01252875. URL: https://clinicaltrialsregister.eu ; Unique identifier: EUDRACT2009-A01280-57.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-8-5)
    Abstract: There is much uncertainty in endovascular treatment (EVT) decisions in patients with acute large vessel occlusion (LVO) and mild neurological deficits. Methods From a prospective, nationwide stroke registry, all patients with LVO and baseline NIHSS & lt;6 presenting within 24 h from the time last known well (LKW) were included. Early neurological deterioration (END) developed before EVT was prospectively collected as an increasing total NIHSS score ≥2 or any worsening of the NIHSS consciousness or motor subscores during hospitalization not related to EVT. Significant hemorrhage was defined as PH2 hemorrhagic transformation or hemorrhage at a remote site. The modified Rankin Scale (mRS) was prospectively collected at 3 months. Results Among 1,083 patients, 149 (14%) patients received EVT after a median of 5.9 [3.6–12.3] h after LKW. In propensity score-matched analyses, EVT was not associated with mRS 0-1 (matched OR 0.99 [0.63–1.54] ) but increased the risk of a significant hemorrhage (matched OR, 4.51 [1.59–12.80]). Extraneous END occurred in 207 (19%) patients after a median of 24.5 h [IQR, 13.5–41.9 h] after LKW (incidence rate, 1.41 [95% CI, 1.23–1.62] per 100 person-hours). END unrelated to EVT showed a tendency to modify the effectiveness of EVT (P-for-interaction, 0.08), which decreased the odds of having mRS 0–1 in mild LVO patients without END (adjusted OR, 0.63 [0.40–0.99] ). Conclusions The use of EVT in patients with acute LVO and low NIHSS scores may require the assessment of individual risks of early deterioration, hemorrhagic complications and expected benefit.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 6
    In: Stroke: Vascular and Interventional Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 3, No. 5 ( 2023-09)
    Abstract: Approximately 10% of patients with acute ischemic stroke with large‐vessel occlusion (LVO) have mild neurological deficits. Although leptomeningeal collaterals (LMCs) are the major determinant of clinical outcomes for patients with acute ischemic stroke with LVO, the contribution of baseline LMC status to subsequent infarct progression in patients with mild stroke with LVO is poorly defined. Methods This observational study included patients with acute anterior circulation LVO and mild stroke symptoms (National Institutes of Health Stroke Scale 〈 6) from a prospectively collected, multicenter, national stroke registry. The Alberta Stroke Program Early Computed Tomography Score was quantified on the initial and follow‐up images. An infarct progression, defined as any Alberta Stroke Program Early Computed Tomography Score decrease between the initial versus follow‐up scans, was categorized as either 0/1/2+. The LMCs on the baseline images were graded as good, fair, or poor. Results Of the 623 included patients (mean age, 67.6±13.4 years; 380 [61.0%] men; 186 [29.9%] with reperfusion treatment), the baseline LMC was graded as good in 331 (53.1%), fair in 219 (35.2%), and poor in 73 (11.7%). The Alberta Stroke Program Early Computed Tomography Score decrement was noted as 0 in 288 (46%) patients, 1 in 154 (24%), and 2+ in 181 (29%). A poor LMC was associated with an infarct progression (adjusted odds ratio, 2.05 [95% CI, 1.22–3.47]). Conclusions Poor collateral blood flow was associated with infarct progression in patients with acute ischemic stroke with LVO and mild symptoms. In this selective population, early assessment of collateral blood flow status can help in early detection of patients susceptible to infarct progression.
    Type of Medium: Online Resource
    ISSN: 2694-5746
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 3144224-9
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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. Suppl_1 ( 2023-02)
    Abstract: Introduction: Perfusion imaging (PI) could guide decision-making for endovascular treatment (EVT) of acute ischemic stroke (AIS). However, PI was underused even in the US before the pivotal EVT trials proved its usefulness in 2018. This study aimed to describe the secular trends of PI utilization and investigate the effectiveness of PI-based EVT in real-world practice. Methods: Using a prospective multicenter (n=17) stroke registry in South Korea, we identified patients with AIS who presented within 24 hours from onset between 2011 and 2021. The study period was divided into 3 epochs: 2011-2014, 2015-2017, and 2018-2021. The study population was divided into the early (arrival within 6 hours) and late window (6-24 hours) groups. Results: A total of 51,650 patients (15,654 patients in 2011-2014, 14,432 patients in 2015-2017, and 21,564 patients in 2018-2021) were analyzed. Utilization of PI decreased in the overall population and early window group ( P trend 〈 0.001); 43.3% and 54.1% in 2011-2014, 40.1% and 44.1% in 2015-2017, and 38.4% and 40.2% in 2018-2021, respectively; but increased in the late window group ( P trend 〈 0.001); 31.3% in 2011-2014, 35.7% in 2015-2017, and 36.5% in 2018-2021. Of 10,872 patients with anterior large-vessel occlusion (aLVO), the EVT rate was not different between patients with and without PI (48.7% vs. 46.6%, P =0.08) in the early window but higher in those with PI than without PI in the late window (29.8% vs. 18.7%, P 〈 0.001). The EVT outcome (3-month mRS 0-2) was not different between patients with and without PI in the early window (44.1% vs. 41.8%, P =0.21) and late window (38.4% vs. 39.2%, P =0.81). Propensity score analysis and instrumental variable analysis with PI rate per center as an instrument will be performed to adjust imbalances between patients with and without PI. Conclusion: Between 2011 and 2021 in South Korea, PI utilization has decreased in patients arriving within 6 hours from onset but has increased in those arriving between 6 and 24 hours. Among patients with aLVO, PI likely increased the EVT rate in the late window but did not in the early window. PI utilization did not seem to affect the EVT outcomes, but in-depth analysis is required.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 8
    In: JAMA Neurology, American Medical Association (AMA), Vol. 78, No. 2 ( 2021-02-01), p. 177-
    Type of Medium: Online Resource
    ISSN: 2168-6149
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2021
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  • 9
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 12 ( 2020-12), p. 3504-3513
    Abstract: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P =0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P =0.23, P interaction =0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively ( P =NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P =0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03354429.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 8 ( 2022-08), p. 2597-2606
    Abstract: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. Methods: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. Results: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. Conclusions: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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