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  • 1
    In: The Lancet Neurology, Elsevier BV, Vol. 17, No. 6 ( 2018-06), p. 509-518
    Type of Medium: Online Resource
    ISSN: 1474-4422
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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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. 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
    detail.hit.zdb_id: 1467823-8
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  • 4
    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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  • 5
    In: Journal of Stroke, Korean Stroke Society, Vol. 22, No. 1 ( 2020-01-31), p. 108-118
    Abstract: Background and purpose Whether pharmacologically altered high-density lipoprotein cholesterol (HDL-C) affects the risk of cardiovascular events is unknown. Recently, we have reported the Prevention of Cardiovascular Events in Asian Patients with Ischaemic Stroke at High Risk of Cerebral Haemorrhage (PICASSO) trial that demonstrated the non-inferiority of cilostazol to aspirin and superiority of probucol to non-probucol for cardiovascular prevention in ischemic stroke patients (clinicaltrials.gov: NCT01013532). We aimed to determine whether on-treatment HDL-C changes by cilostazol and probucol influence the treatment effect of each study medication during the PICASSO study.Methods Of the 1,534 randomized patients, 1,373 (89.5%) with baseline cholesterol parameters were analyzed. Efficacy endpoint was the composite of stroke, myocardial infarction, and cardiovascular death. Cox proportional hazards regression analysis examined an interaction between the treatment effect and changes in HDL-C levels from randomization to 1 month for each study arm.Results One-month post-randomization mean HDL-C level was significantly higher in the cilostazol group than in the aspirin group (1.08 mmol/L vs. 1.00 mmol/L, 〈 i 〉 P 〈 /i 〉 〈 0.001). The mean HDL-C level was significantly lower in the probucol group than in the non-probucol group (0.86 mmol/L vs. 1.22 mmol/L, 〈 i 〉 P 〈 /i 〉 〈 0.001). These trends persisted throughout the study. In both study arms, no significant interaction was observed between HDL-C changes and the assigned treatment regarding the risk of the efficacy endpoint.Conclusions Despite significant HDL-C changes, the effects of cilostazol and probucol treatment on the risk of cardiovascular events were insignificant. Pharmacologically altered HDL-C levels may not be reliable prognostic markers for cardiovascular risk.
    Type of Medium: Online Resource
    ISSN: 2287-6391 , 2287-6405
    Language: English
    Publisher: Korean Stroke Society
    Publication Date: 2020
    detail.hit.zdb_id: 2814366-8
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 51, No. 3 ( 2020-03), p. 931-937
    Abstract: Although cilostazol has shown less hemorrhagic events than aspirin, only marginal difference was observed in hemorrhagic stroke events among patients at high risk for cerebral hemorrhage. To identify patients who would most benefit from cilostazol, this study analyzed interactions between treatment and subgroups of the PICASSO trial (Prevention of Cardiovascular Events in Asian Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage). Methods— Ischemic stroke patients with a previous intracerebral hemorrhage or multiple microbleeds were randomized to treatment with cilostazol or aspirin and followed up for a mean 1.8 years. Efficacy, defined as the composite of any stroke, myocardial infarction, and vascular death, and safety, defined as the incidence of hemorrhagic stroke, were analyzed in the 2 groups. Interactions between treatment and age, sex, presence of hypertension and diabetes mellitus, index of high-risk cerebral hemorrhage, and white matter lesion burden were analyzed for primary and key secondary outcomes. Changes in vital signs and laboratory results were compared in the 2 groups. Results— Among all 1534 patients enrolled, a significant interaction between treatment group and index of high risk for cerebral hemorrhage on hemorrhagic stroke ( P for interaction, 0.03) was observed. Hemorrhagic stroke was less frequent in the cilostazol than in the aspirin group in patients with multiple microbleeds (1 versus 13 events; hazard ratio, 0.08 [95% CI, 0.01–0.61]; P =0.01). A marginal interaction between treatment group and white matter change on any stroke ( P for interaction, 0.08) was observed. Cilostazol reduced any stroke significantly in patients with mild (5 versus 16 events; hazard ratio, 0.36 [95% CI, 0.13–0.97]; P =0.04)-to-moderate (16 versus 32 events; hazard ratio, 0.50 [95% CI, 0.29–0.92]; P =0.03) white matter changes. Heart rate and HDL (high-density lipoprotein) cholesterol level were significantly higher in the cilostazol group than in the aspirin group at follow-up. Conclusions— Cilostazol may be more beneficial for ischemic stroke patients with multiple cerebral microbleeds and before white matter changes are extensive. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01013532.
    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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  • 7
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 12 ( 2012-12), p. 3278-3283
    Abstract: Unclear-onset strokes are generally excluded from time-based thrombolytic therapy. We examined the safety and feasibility of magnetic resonance imaging-based reperfusion therapy in unclear-onset stroke. Methods— This prospective, multicenter, single-arm study screened consecutive unclear-onset stroke patients within 6 hours of symptom detection. Patients with perfusion-diffusion mismatch 〉 20% and negative or subtle fluid-attenuated inversion recovery changes were treated with intravenous tissue plasminogen activator, intra-arterial therapy, or a combination. The safety outcome was symptomatic intracranial hemorrhage within 48 hours after treatment. The primary efficacy outcome was a 3-month modified Rankin Scale score of 0 to 2. Controls were untreated unclear-onset stroke patients prospectively captured in stroke registries. Results— Of 430 unclear-onset stroke patients, 83 (19.3%) received reperfusion therapy (mean age, 67.5 ± 10.4 years; males, 66.3%; median baseline National Institutes of Health Stroke Scale, 14). Symptomatic intracranial hemorrhage with any neurological decline developed in 5 patients (6.0%). Symptomatic intracranial hemorrhage with National Institutes of Health Stroke Scale worsening ≥4 developed in 3 patients (3.6%). Thirty-seven patients (44.6%) achieved modified Rankin Scale score of 0 to 2, and 24 (28.9%) had modified Rankin Scale score of 0 to 1. Female, baseline National Institutes of Health Stroke Scale score, no immediate or early recanalization, and more white blood cells were independent predictors of poor outcome. Compared with untreated controls, the treated group was significantly associated with good outcomes of modified Rankin Scale score of 0 to 2 after adjusting for age, sex, and baseline National Institutes of Health Stroke Scale in logistic regression analysis (odds ratio, 2.25; 95% CI, 1.14–4.49). Conclusions— In unclear-onset stroke patients, magnetic resonance imaging-based reperfusion therapy was feasible and safe. Randomized controlled trials are warranted to confirm the benefit of reperfusion therapy for unclear-onset stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 8
    In: Journal of Clinical Neurology, XMLink, Vol. 8, No. 4 ( 2012), p. 265-
    Type of Medium: Online Resource
    ISSN: 1738-6586 , 2005-5013
    Language: English
    Publisher: XMLink
    Publication Date: 2012
    detail.hit.zdb_id: 2500489-X
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  • 9
    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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  • 10
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. suppl_1 ( 2013-02)
    Abstract: Background: Cardioembolic (CE) strokes are more disabling and more fatal than non-CE strokes. Multiple prognostic factors have been recognized, but the magnitude of their relative contribution has not been well explored. Methods: Using a stroke outcome registry, we compared the outcomes of CE and non-CE strokes. The relative contribution of prognostic factors was assessed with multivariable models and model fitness improvement using -2 log-likelihood and Nagelkerke’s R 2 . Results: A total of 1233 patients were included in this analysis. As compared to non-CE strokes, CE strokes had less mRS 0-2 outcomes (47.2% vs 68.5%, p 〈 0.001), less mRS 0-1 outcomes (33.7% vs 53.5%, p 〈 0.001), more mRS 5-6 outcomes (32.1% vs 10.9%, p 〈 0.001), and higher mortality (19.2% vs 5.2%, p 〈 0.001). When adjusting either baseline demographics or poststroke complications, the outcome differences remained significant. However, adjusting initial NIHSS score alone abolished the differences in mRS 0-2 outcome (Figure) and mRS 0-1 and mRS 5-6 outcomes. For mRS 0-2 outcome, the differences in -2 log-likelihood and Nagelkerke’s R 2 between univariable model and multivariable model were greater with adjusting NIHSS alone (-2 log-likelihood difference, 418; Nagelkerke’s R 2 difference, 38.7%) than with adjusting baseline demographics (184; 17.7%) or poststroke complication (279; 27.3%). Further adjustment of baseline demographics and poststroke complication to the initial NIHSS score adjustment resulted in a small shift of odds ratio. The decrement of -2 log-likelihood and the Nagelkerke’s R 2 of the model adjusting initial NIHSS score alone approached 70.2% and 76.7% of the model adjusting baseline demographics, poststroke complication, and initial NIHSS score. Conclusion: Greater stroke severity predominates over all other factors for the worse outcome of CE stroke.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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