Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Jiwei, Cheng; Zhang, Xiaojing; Cheng, Li-Shan; Li, Guo-Yi; Zhang, Lijun; Ji, Kangxiang; Zhao, Qing; Bai, Yu

doi:10.1016/j.jstrokecerebrovasdis.2017.09.014

Cited by 32 publications

(24 citation statements)

References 42 publications

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“…In addition, 51.5% of our AIS cohort who were patients aged > 80 years received low dose tPA (0.6 mg/kg). This 'aging' concept may explain in part the strong association between lower tPA dose and the post-tPA 3-month mortality; this is more likely so, considering cumulative evidence of the safety, efficacy and therapeutic non-inferiority of low dose tPA, compared to standard dose [29][30][31] . In our model, the predictive value for tPA dose suggests the applicability of our ANN model to optimize the tPA dose for individual patients.…”

Section: Discussionmentioning

confidence: 99%

Artificial neural network based prediction of postthrombolysis intracerebral hemorrhage and death

Chung

Chan

Bamodu

et al. 2020

Sci Rep

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Despite the salient benefits of the intravenous tissue plasminogen activator (tPA), symptomatic intracerebral hemorrhage (sICH) remains a frequent complication and constitutes a major concern when treating acute ischemic stroke (AIS). This study explored the use of artificial neural network (ANN)-based models to predict sICH and 3-month mortality for patients with AIS receiving tPA. We developed ANN models based on evaluation of the predictive value of pre-treatment parameters associated with sICH and mortality in a cohort of 331 patients between 2009 and 2018. The ANN models were generated using eight clinical inputs and two outputs. The generalizability of the model was validated using fivefold cross-validation. The performance of each model was assessed according to the accuracy, precision, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). After adequate training, the ANN predictive model AUC for sICH was 0.941, with accuracy, sensitivity, and specificity of 91.0%, 85.7%, and 92.5%, respectively. The predictive model AUC for 3-month mortality was 0.976, with accuracy, sensitivity, and specificity of 95.2%, 94.4%, and 95.5%, respectively. The generated ANN-based models exhibited high predictive performance and reliability for predicting sICH and 3-month mortality after thrombolysis; thus, its clinical application to assist decision-making when administering tPA is envisaged.

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Section: Discussionmentioning

confidence: 99%

Artificial neural network based prediction of postthrombolysis intracerebral hemorrhage and death

Chung

Chan

Bamodu

et al. 2020

Sci Rep

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“…As a therapeutic agent, tPA is an effective and approved Food and Drug Administration (FDA) treatment for acute ischemic stroke. tPA converts inactive plasminogen to the active protease plasmin which dissolves fibrin clots into soluble degradation products [1]. However, growing evidence implies that tPA has a close relationship with cognitive function and dementia [2].…”

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confidence: 99%

Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice

Yu¹,

Venkat²,

Chopp³

et al. 2019

Aging and disease

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Tissue plasminogen activator (tPA) is a serine protease primarily involved in mediating thrombus breakdown and regulating catabolism of amyloid-beta (Aβ). The aim of this study is to investigate age-dependent decline of endogenous tPA and the effects of tPA decline on glymphatic function and cognitive outcome in mice. Male, young (3m), adult (6m) and middle-aged (12m) C57/BL6 (wild type) and tPA knockout (tPA -/- ) mice were subject to a battery of cognitive tests and white matter (WM) integrity, neuroinflammation, and glymphatic function were evaluated. Adult WT mice exhibit significantly decreased brain tPA level compared to young WT mice and middle-aged WT mice have significantly lower brain tPA levels than young and adult WT mice. Middle-aged WT mice exhibit significant neuroinflammation, reduced WM integrity and increased thrombin deposition compared to young and adult mice, and increased blood brain barrier (BBB) permeability and reduced cognitive ability compared to young WT mice. In comparison to adult WT mice, adult tPA -/- mice exhibit significant BBB leakage, decreased dendritic spine density, increased thrombin deposition, neuroinflammation, and impaired functioning of the glymphatic system. Compared to age-matched WT mice, adult and middle-aged tPA -/- mice exhibit significantly increased D-Dimer expression and decreased perivascular Aquaporin-4 expression. Compared to age-matched WT mice, young, adult and middle-aged tPA -/- mice exhibit significant cognitive impairment, axonal damage, and increased deposition of amyloid precursor protein (APP), Aβ, and fibrin. Endogenous tPA may play an important role in contributing to aging induced cognitive decline, axonal/WM damage, BBB disruption and glymphatic dysfunction in the brain.

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“…Despite significant diagnostic and therapeutic advances in recent decades, acute ischemic stroke (AIS) remains one of the leading causes of morbidity and mortality worldwide (1). Intravenous thrombolysis (IVT) is an effective recanalization strategy in AIS (2), and appropriately applied IVT within the time window of AIS is associated with improved functional outcome and survival in these patients. However, IVT has also been associated with an increased risk of symptomatic intracranial hemorrhage (SIH) in AIS patients, particularly in high-risk patients (2).…”

Section: Introductionmentioning

confidence: 99%

“…Intravenous thrombolysis (IVT) is an effective recanalization strategy in AIS (2), and appropriately applied IVT within the time window of AIS is associated with improved functional outcome and survival in these patients. However, IVT has also been associated with an increased risk of symptomatic intracranial hemorrhage (SIH) in AIS patients, particularly in high-risk patients (2). Statins are a category of cholesterollowering medications which have become the cornerstone for the primary and secondary prevention of atherosclerotic cardiovascular diseases (3,4).…”

Section: Introductionmentioning

confidence: 99%

Premorbid Use of Statin and Outcome of Acute Ischemic Stroke After Intravenous Thrombolysis: A Meta-Analysis

Liu

Wang

et al. 2020

Front. Neurol.

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Background: The association between the premorbid use of statin and the early outcomes of acute ischemic stroke (AIS) after intravenous thrombolysis (IVT) remains uncertain. We performed a meta-analysis of observational studies to evaluate the influence of the premorbid use of statin on functional outcome and symptomatic intracranial hemorrhage (SIH) in AIS after IVT. Methods: Relevant studies were identified by search of PubMed, Embase, and Cochrane's Library databases. Only studies with multivariate analyses were included. A random-effect model, incorporating inter-study heterogeneity, was used to pool the results. Results: Twenty observational studies with 20,752 AIS patients who were treated with IVT were included. The pooled results showed that the premorbid use of statin was not associated with improved 3-month favorable functional outcome [odds ratio (OR): 1.05, 95% confidence interval (CI): 0.87–1.26, p = 0.60, I 2 = 52%), 3-month functional independence (OR: 1.13, 95% CI: 0.96–1.33, p = 0.15, I 2 = 52%), or 3-month mortality (OR: 1.12, 95% CI: 0.94–1.34, p = 0.20, I 2 = 20%). Moreover, the premorbid use of statin was associated with an increased risk of SIH in AIS after IVT (OR: 1.48, 95% CI: 1.12–1.95, p = 0.006, I 2 = 60%). Subgroup analyses according to study design, adjustment of baseline low-density lipoprotein cholesterol, and definitions of SIH showed consistent results ( p -values for subgroup difference all >0.05). Conclusions: The premorbid use of statin is not associated with improved functional outcomes or mortality but is associated with a higher risk of SIH in AIS patients after IVT.

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Low-Dose Tissue Plasminogen Activator in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Cited by 32 publications

References 42 publications

Artificial neural network based prediction of postthrombolysis intracerebral hemorrhage and death

Artificial neural network based prediction of postthrombolysis intracerebral hemorrhage and death

Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice

Premorbid Use of Statin and Outcome of Acute Ischemic Stroke After Intravenous Thrombolysis: A Meta-Analysis

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