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1.
Indications and Evidence for Dual Antiplatelet Therapy After Acute Ischemic Stroke.
Ringler, J, Steck, M, Shah, SP, Chester, KW
Critical care nursing quarterly. 2020;(2):122-137
Abstract
The antiplatelet landscape for the secondary prevention of ischemic stroke has changed significantly over the past decade. Poststroke dual antiplatelet regimens are becoming increasingly routine as supported by recent literature and guideline recommendations. Dual antiplatelet therapy after stroke generally consists of aspirin and clopidogrel and is considered in the short term after stroke in select populations including those with mild stroke or transient ischemic attack and in patients with severe intracranial atherosclerosis. When initiating dual antiplatelet therapy, factors that may increase a patient's risk of bleeding must be weighed against the patient's risk of future ischemic events. This review focuses on antiplatelet medications available in the United States with the aim to provide a summary of the available literature on poststroke dual antiplatelet therapy, pharmacological nuances of the agents, and reversal of antiplatelets in the setting of intracerebral hemorrhage.
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2.
The Benefits and Risks of Statin Therapy in Ischemic Stroke: A Review of the Literature.
Zhao, W, Xiao, ZJ, Zhao, SP
Neurology India. 2019;(4):983-992
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Abstract
Statins are effective cholesterol-lowering drugs for reducing the risks of mortality and morbidity of cardiovascular diseases. Increasing evidence has shown that statin use is associated with a significant beneficial effect in patients with ischemic stroke. Both pre-stroke and post-stroke statin use has been found to be beneficial in ischemic stroke. Furthermore, good adherence is associated with a better clinical outcome, and statin withdrawal is associated with a poor functional outcome in patients with ischemic stroke. High-intensity statin therapy is advocated for the treatment of ischemic stroke. However, there are concerns regarding the adverse effects associated with statin use in ischemic stroke such as intracranial hemorrhage. In this review, we summarize the beneficial effect of statin use in ischemic stroke and discuss the potential risks associated with statin therapy.
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3.
Ischaemic stroke.
Campbell, BCV, De Silva, DA, Macleod, MR, Coutts, SB, Schwamm, LH, Davis, SM, Donnan, GA
Nature reviews. Disease primers. 2019;(1):70
Abstract
Stroke is the second highest cause of death globally and a leading cause of disability, with an increasing incidence in developing countries. Ischaemic stroke caused by arterial occlusion is responsible for the majority of strokes. Management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy, which both reduce disability but are time-critical. Accordingly, improving the system of care to reduce treatment delays is key to maximizing the benefits of reperfusion therapies. Intravenous thrombolysis reduces disability when administered within 4.5 h of the onset of stroke. Thrombolysis also benefits selected patients with evidence from perfusion imaging of salvageable brain tissue for up to 9 h and in patients who awake with stroke symptoms. Endovascular thrombectomy reduces disability in a broad group of patients with large vessel occlusion when performed within 6 h of stroke onset and in patients selected by perfusion imaging up to 24 h following stroke onset. Secondary prevention of ischaemic stroke shares many common elements with cardiovascular risk management in other fields, including blood pressure control, cholesterol management and antithrombotic medications. Other preventative interventions are tailored to the mechanism of stroke, such as anticoagulation for atrial fibrillation and carotid endarterectomy for severe symptomatic carotid artery stenosis.
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4.
Intravenous tPA (Tissue-Type Plasminogen Activator) in Patients With Acute Ischemic Stroke Taking Non-Vitamin K Antagonist Oral Anticoagulants Preceding Stroke.
Jin, C, Huang, RJ, Peterson, ED, Laskowitz, DT, Hernandez, AF, Federspiel, JJ, Schwamm, LH, Bhatt, DL, Smith, EE, Fonarow, GC, et al
Stroke. 2018;(9):2237-2240
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Abstract
Background and Purpose- Although there are no trials or large cohorts to inform clinical care, current guidelines caution against giving intravenous tPA (tissue-type plasminogen activator) to patients with acute ischemic stroke who are taking non-vitamin K antagonist oral anticoagulants (NOACs). We performed a literature review of intravenous tPA in patients treated with NOACs preceding stroke. Methods- A literature search of PubMed was performed encompassing January 2010 to March 2018. Patient characteristics, timing of last medication intake, laboratory testing, use of reversal, and outcomes ≤3 months after discharge were summarized. Results- We identified 55 studies with 492 NOAC patients receiving tPA (dabigatran, 181; rivaroxaban, 215; apixaban, 40; and unspecified NOAC, 56). Among patients with complete data, the median time from the last NOAC intake to symptom onset was 8 hours (interquartile range, 2.5-14.5), with 55.2% (80/145) within 12 hours. Few patients underwent sensitive laboratory tests, such as thrombin time, diluted thrombin time, or anti-Xa assays before tPA administration. The overall observed rates of symptomatic intracranial hemorrhage, mortality, and favorable outcomes (National Institutes of Health Stroke Scale score, ≤1; modified Rankin Scale score, 0-2; or neurological improvement in the National Institutes of Health Stroke Scale score, ≥8 points) were 4.3% (20/462), 11.3% (48/423), and 43.7% (164/375), respectively. Among dabigatran-treated patients, reversal with idarucizumab was associated with fewer symptomatic intracranial hemorrhage (4.5% [2/44] versus 7.4% [8/108]; unadjusted odds ratio, 0.60; 95% CI, 0.12-2.92), death (4.5% [2/44] versus 12.0% [13/108]; unadjusted odds ratio, 0.35; 95% CI, 0.08-1.61), and more favorable outcomes (79.1% [34/43] versus 39.2% [29/74]; unadjusted odds ratio, 5.86; 95% CI, 2.45-14.00), although the differences were not statistically significant for symptomatic intracranial hemorrhage and death. Conclusions- These preliminary observations suggest that tPA may be reasonably well tolerated without prohibitive risks of bleeding complications in selected patients on NOACs. Reversal of anticoagulant effects by idarucizumab for dabigatran-treated patients before tPA is an emerging strategy that was associated with more favorable outcomes.
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5.
Hemostasis in the Very Young.
Kenet, G, Barg, AA, Nowak-Göttl, U
Seminars in thrombosis and hemostasis. 2018;(7):617-623
Abstract
Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed.
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6.
Cerebrolysin: a multi-target drug for recovery after stroke.
Brainin, M
Expert review of neurotherapeutics. 2018;(8):681-687
Abstract
Cerebrolysin is a neuropeptide preparation with neurotrophic effects and promotes recovery after brain injury. Its preclinical profile promises wide applications due to its multi-target effects. Currently, Cerebrolysin is used for treatment of cerebral ischemia and neurodegeneration. Areas covered: In stroke, earlier clinical trials with Cerebrolysin were performed mostly in mildly affected stroke populations, which usually have a favorable prognosis. Due to this selection, a floor or ceiling effect of recovery measures in the mild cases may have prevented to show a clear benefit between treatment groups. In contrast, subgroup analyses of more severely affected patients reveal a strikingly positive effect for enhanced recovery. Based on the findings from several studies, it became evident that the effect size of Cerebrolysin was increasing with stroke severity. Other controlled studies showed that Cerebrolysin can be safely used in combination with thrombolysis. More recently, Cerebrolysin has been tested not only for neuroprotection but also for its neurorecovery potential and also showed efficacy in patients with moderate to severe strokes. Expert commentary: Cerebrolysin shows a benefit mostly in moderate to severe ischemic stroke patients and an overall significant effect for functional recovery when combined with neurorehabilitation versus neurorehabilitation alone. This gives lead to the planning of a more rigorous study design in the future.
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7.
Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation.
Korompoki, E, Filippidis, FT, Nielsen, PB, Del Giudice, A, Lip, GYH, Kuramatsu, JB, Huttner, HB, Fang, J, Schulman, S, Martí-Fàbregas, J, et al
Neurology. 2017;(7):687-696
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Abstract
OBJECTIVE To perform a systematic review and meta-analysis of studies reporting recurrent intracranial hemorrhage (ICH) and ischemic stroke (IS) in ICH survivors with atrial fibrillation (AF) during long-term follow-up. METHODS A comprehensive literature search including MEDLINE, EMBASE, Cochrane library, clinical trials registry was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We considered studies capturing outcome events (ICH recurrence and IS) for ≥3 months and treatment exposure to vitamin K antagonists (VKAs), antiplatelet agents (APAs), or no antithrombotic medication (no-ATM). Corresponding authors provided aggregate data for IS and ICH recurrence rate between 6 weeks after the event and 1 year of follow-up for each treatment exposure. Meta-analyses of pooled rate ratios (RRs) were conducted with the inverse variance method. RESULTS Seventeen articles met inclusion criteria. Seven observational studies enrolling 2,452 patients were included in the meta-analysis. Pooled RR estimates for IS were lower for VKAs compared to APAs (RR = 0.45, 95% confidence interval [CI] 0.27-0.74, p = 0.002) and no-ATM (RR = 0.47, 95% CI 0.29-0.77, p = 0.002). Pooled RR estimates for ICH recurrence were not significantly increased across treatment groups (VKA vs APA: RR = 1.34, 95% CI 0.79-2.30, p = 0.28; VKA vs no-ATM: RR = 0.93, 95% CI 0.45-1.90, p = 0.84). CONCLUSIONS In observational studies, anticoagulation with VKA is associated with a lower rate of IS than APA or no-ATM without increasing ICH recurrence significantly. A randomized controlled trial is needed to determine the net clinical benefit of anticoagulation in ICH survivors with AF.
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[Neurotrophic effects of lithium stimulate the reduction of ischemic and neurodegenerative brain damage].
Pronin, AV, Gogoleva, IV, Torshin, IY, Gromovа, OA
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2016;(2):99-108
Abstract
For over 60 years, high doses of lithium (hundreds of milligrams of elemental lithium) have being used to treat bipolar disorder. However, only during the past 20 years the relevant basic and clinical studies have shown that neuroprotective and neurotrophic effects of lithium are possible in much smaller doses ( hundreds of micrograms of elemental lithium). These data indicate a significant potential for the clinical applications of lithium-based drugs in modern neurology for the purposes of prevention and treatment of neurodegenerative and ischemic pathologies. Pharmacological and molecular biology studies indicated that the inhibition of glycogen synthase kinase-syntentase-3 (GSK-3) and induction of brain-derived neurotrophic factors are the main mechanisms of neurotropic actions of lithium. Also, by inhibiting the NMDA receptors, lithium regulates the calcium homeostasis and inhibits the activation of calcium-dependent apotosis. These and other molecular mechanisms of lithium action protect neurons from ischemia and neurodegeneration thus contributing to a significant reduction of neurological deficit in various models of stroke and neurodegenerative diseases.
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9.
Phytochemicals in Ischemic Stroke.
Kim, J, Fann, DY, Seet, RC, Jo, DG, Mattson, MP, Arumugam, TV
Neuromolecular medicine. 2016;(3):283-305
Abstract
Stroke is the second foremost cause of mortality worldwide and a major cause of long-term disability. Due to changes in lifestyle and an aging population, the incidence of stroke continues to increase and stroke mortality predicted to exceed 12 % by the year 2030. However, the development of pharmacological treatments for stroke has failed to progress much in over 20 years since the introduction of the thrombolytic drug, recombinant tissue plasminogen activator. These alarming circumstances caused many research groups to search for alternative treatments in the form of neuroprotectants. Here, we consider the potential use of phytochemicals in the treatment of stroke. Their historical use in traditional medicine and their excellent safety profile make phytochemicals attractive for the development of therapeutics in human diseases. Emerging findings suggest that some phytochemicals have the ability to target multiple pathophysiological processes involved in stroke including oxidative stress, inflammation and apoptotic cell death. Furthermore, epidemiological studies suggest that the consumption of plant sources rich in phytochemicals may reduce stroke risk, and so reinforce the possibility of developing preventative or neuroprotectant therapies for stroke. In this review, we describe results of preclinical studies that demonstrate beneficial effects of phytochemicals in experimental models relevant to stroke pathogenesis, and we consider their possible mechanisms of action.
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Autophagy in cerebral ischemia and the effects of traditional Chinese medicine.
Huang, XP, Ding, H, Lu, JD, Tang, YH, Deng, BX, Deng, CQ
Journal of integrative medicine. 2015;(5):289-96
Abstract
Autophagy is a lysosome-mediated degradation process for non-essential or damaged cellular constituents, playing an important homeostatic role in cell survival, differentiation and development to maintain homeostasis. Autophagy is involved in tumors as well as neurodegenerative, cardiovascular and cerebrovascular diseases. Recently, active compounds from traditional Chinese medicine (TCM) have been found to modulate the levels of autophagy in tumor cells, nerve cells, myocardial cells and endothelial cells. Ischemic stroke is a major cause of neurological disability and places a heavy burden on family and society. Regaining function can significantly reduce dependence and improve the quality of life of stroke survivors. In healthy cells, autophagy plays a key role in adapting to nutritional deprivation and eliminating aggregated proteins, however inappropriate activation of autophagy may lead to cell death in cerebral ischemia. This paper reviews the process and the molecular basis of autophagy, as well as its roles in cerebral ischemia and the roles of TCM in modulating its activity.