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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic stroke exacts a heavy toll in death and disability. Important progress have been made in terms of secondary prevention. Care of patients with acute stroke can also be improved. In 1996, the FDA approved Alteplase or rt-PA as a safe and effective treatment for stroke when given within 3 hours of the onset of neurological deficit. More than 10 years later, this treatment is still underused, mostly because of poor knowledge in the general population regarding stroke symptoms and implications, and inefficient emergency care and organisation. Organisation of primary stroke centers results in optimization in the care of patients with acute stroke, and improvement in outcomes, with reduction in death, dependency and need for institutional care.
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PMID:[Time is brain]. 1866 90

In Japan, the intravenous tissue plasminogen activator (t-PA) Alteplase (0.6 mg/kg) administration of the within 3 h of the onset of acute ischemic stroke was approved for therapeutic use in the year 2006. t-PA induces thrombolysis in patients with acute ischemic stroke, and this method has gradually gained recognition among physicians and the general population. However, the number of patients who were treated using Alteplase is low (4,000-5,000 patients/year), and this figure accounts for only 2-3% of the annual number of cases of ischemic stroke. There is little doubt that Alteplase treatment is a potentially effective modality for some patients with acute ischemic stroke. The post-marketing surveillance of 4,749 Japanese patients treated using Alteplase showed that 33% of the patients had modified Rankin scale (mRS) scores of 0-1, 17% of patiens died and 4.5% presented with symptomatic intracerebral hemorrhage (ICH); these results were comparable to those from other countries. The expansion of the therapeutic time window has been a matter of concern. The investigators of the European Cooperative Acute Stroke Study (ECASS) have reported that there was significant improvement in the clinical outcomes of patients with acute ischemie stroke when Alteplase was administered 3-4.5 h after the onset of the symptoms. Mismatches in perfusion- and diffusion-weighted (DW) magnetic resonance imaging (MRI) images have been used for selecting patients 3 h after the onset of symptoms, and the findings from MRI, dwimages (DWI) and MR angiography are practical predictors of t-PA therapy within 3 h of onset. The Middle Cerebral Artery Embolism Local Fibrinolytic Intervention Trial (MELT) Japan study showed that local intra-arterial fibrinolysis is effective in patients with embolic MCA occlusion within 6 h of the onset of symptoms. Combining the initiation of intravenous t-PA administration with further intra-arterial fibrinolysis or mechanical thrombolectomy may improve the recanalization rate. Thrombolysis in combination with ultrasound-enhanced clot lysis is another attractive therapy. In Japan the neuroprotective agent edaravone (radical scavenger) is commonly used in combination with t-PA, and it is expected to decrease the hemorrhagic transformation after t-PA administration. Acute cerebral ischemic symptoms may occasionally precede thoracic aortic dissection. Thoracic aortic dissection after t-PA administration may prove to be fatal, and it is an important disorder that must be differentially diagnosed.
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PMID:[Thrombolysis by intravenous tissue plasminogen activator (t-PA)--current status and future direction]. 1917 6

Japan Alteplase Clinical Trial (J-ACT), a prospective multicenter clinical trial, demonstrated good clinical outcome in patients treated with 0.6 mg/kg of alteplase, being similar to that with 0.9 mg/kg of alteplase in the National Institute of Neurological Disorders and Stroke (NINDS) study. On that basis, intravenous aplteplase therapy was approved in Japan in October, 2005. This therapy resulted in better efficacy and similar safety in our stroke care unit (SCU) as compared to J-ACT or other clinical studies performed outside Japan. Our nation-wide survey demonstrated that the approval of the therapy resulted in dramatic changes in the processes of management for acute stroke patients. Preliminary results of the post-marketing surveillance study of alteplase in Japan suggested similar efficacy and safety profiles of the therapy to those reported by a European study, Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST). There are several limitations and problems in the therapy that will be overcome by new therapeutic strategies including the development of new-generation therombolytic agents having longer therapeutic time window, applications of magnetic resonance imaging techniques, and combination therapies with neuroprotective agents, sonothrombolysis, intraarterial application of the agent, or mechanical thrombectomy.
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PMID:[New era has begun since the approval of thrombolytic therapy for acute ischemic stroke in Japan]. 1919 7

The US Food and Drug Administration (FDA) approved the use of intravenous (IV) recombinant tissue plasminogen activator (rt-PA) in 1996, on the basis of the results of the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study. IV rt-PA therapy at a dose of 0.9 mg/kg has been approved internationally for the treatment of hyperacute ischemic stroke. After a dose comparison study using duteplase and a multicenter study using a single dose of alteplase (Japan Alteplase Clinical Trial: J-ACT), the administration of IV rt-PA therapy at a dose of 0.6 mg/kg was approved in Japan in 2005. Immediately after the approval, the Japan Stroke Society published the Japanese guidelines for this low-dose therapy. Two years after the approval in Japan, the outcome of IV rt-PA therapy in Japan was observed to be comparable to that of NINDS rt-PA therapy and to those published in studies based in Western nations. Several trials have reported predictors of unfavorable outcome for IV rt-PA therapy. Patients with severe strokes (higher NIHSS score, coma), higher age at disease onset, aortic arch dissection, higher blood pressure, higher blood sugar, occlusion of the internal carotid artery (ICA) or tandem lesion of the left ICA and right middle cerebral artery (MCA), or the presence of major early ischemic changes as observed upon computed tomography (CT) or magnetic resonance imaging (MRI), showed a greater probability for unfavorable response to treatment. The results of the randomised 2008 trial conducted by the third European Cooperative Acute Stroke Study (ECASS III) suggested that treatment with IV rt-PA administered 3-4.5 hours after symptom onset can still induce significant improvement in clinical outcomes after an acute ischemic stroke as opposed to a placebo. MRI-based thrombolysis might be safer than standard CT-based thrombolysis. A combination of reperfusion therapies, IV rt-PA and sonothrombolysis, neuroprotective agents or antiplatelet agents may be effective. However, currently available data do not provide conclusive evidence for the safety or efficacy of these combination therapies. Patients having ICA occlusion may require alternatives including a higher dose of alteplase, combined IV/IA thrombolysis, or possibly mechanical thrombectomy by using a thrombus-removal device.
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PMID:[Prospects of thrombolytic therapy for acute ischemic stroke]. 1980 99

After the success of the 1995 National Institutes of Neurological Disorders and Stroke (NINDS) study using intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA, alteplase) within 3 hours in acute stroke, this therapy was approved worldwide and has been a standard therapy for acute stroke patients. In Japan, IV alteplase at a dose of 0.6 mg/kg was approved in 2005 after a multicenter study using this low dose of alteplase (Japan Alteplase Clinical Trial [J-ACT]). IV rt-PA can drastically improve stroke outcomes. However, more than half of treated patients are not independent in the chronic stage. In addition, the therapeutic time window was so limited that many stroke patients do not have a chance to receive the therapy. In 2008, European Cooperative Acute Stroke Study III showed that IV rt-PA administered between 3 and 4.5 hours after stroke onset significantly improved clinical outcomes in stroke patients; the success resulted in the renewal of recommendation in guidelines in Europe, Canada, and the United States. Several therapeutic strategies, including endovascular therapy, sonothrombolysis, and neuroprotective therapy, may improve the efficacy of IV rt-PA.
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PMID:[Intravenous rt-PA therapy for acute ischemic stroke: efficacy and limitations]. 2003 Feb 14

Alteplase (tissue plasminogen activator, tPA) is currently the only FDA-approved treatment that can be given to acute ischemic stroke (AIS) patients if patients present within 3 h of an ischemic stroke. After 14 years of alteplase clinical research, evidence now suggests that the therapeutic treatment window can be expanded 4.5 h, but this is not formally approved by the FDA. Even though there remains a significant risk of intracerebral hemorrhage associated with alteplase administration, there is an increased chance of favorable outcome with tPA treatment. Over the last 30 years, the use of preclinical models has assisted with the search for new effective treatments for stroke, but there has been difficulty with the translation of efficacy from animals to humans. Current research focuses on the development of new and potentially useful thrombolytics, neuroprotective agents, and devices which are also being tested for efficacy in preclinical and clinical trials. One model in particular, the rabbit small clot embolic stroke model (RSCEM) which was developed to test tPA for efficacy, remains the only preclinical model used to gain FDA approval of a therapeutic for stroke. Correlative analyses from existing preclinical translational studies and clinical trials indicate that there is a therapeutic window ratio (ARR) of 2.43-3 between the RSCEM and AIS patients. In conclusion, the RSCEM can be used as an effective translational tool to gauge the clinical potential of new treatments.
Transl Stroke Res 2010 Jun
PMID:Translational stroke research using a rabbit embolic stroke model: a correlative analysis hypothesis for novel therapy development. 2053 48

The aim of the present study was to identify factors associated with functional outcome, mortality, and symptomatic intracranial hemorrhage (sICH) in patients from the Japan Alteplase Clinical Trial (J-ACT) data set with ischemic stroke treated with intravenous (IV) 0.6 mg/kg alteplase within 3 hours after onset. The patient sample comprised 103 patients from the J-ACT, a multicenter, single-dose, open-label cohort study conducted to verify the efficacy and safety of IV 0.6 mg/kg alteplase in treating acute hemispheric stroke. The effects of 21 patient baseline characteristics on a favorable outcome (as evaluated by modified Rankin scale [mRS] score of 0-1 after 3 months), death within 3 months, and incidence of sICH within 36 hours after the start of treatment were examined by univariate analysis and stepwise logistic regression analysis. The baseline characteristics associated with a favorable outcome in univariate analysis included age and National Institutes of Health Stroke Scale (NIHSS) score. The factors associated with death included age and the NIHSS score. No factors were significantly associated with sICH. In stepwise logistic regression analysis, age and NIHSS score significantly predicted both favorable outcome and death. No factors significantly predicted sICH. Age and baseline NIHSS score were independent predictors for both favorable outcome and death. Although these factors are consistent with those found to be predictors in studies on IV 0.9 mg/kg alteplase, there were no factors predicting outcomes specific for IV 0.6 mg/kg alteplase.
J Stroke Cerebrovasc Dis 2011 Nov
PMID:Factors predicting outcome in stroke patients treated with 0.6 mg/kg alteplase: evidence from the Japan Alteplase Clinical Trial (J-ACT). 2071 35

Alteplase is the only drug licensed for acute ischemic stroke, and in this formulation, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) is stabilized in a solution of L-arginine. Improved functional outcomes after alteplase administration have been shown in clinical trials, along with improved histological and behavioral measures in experimental models of embolic stroke. However, in animal models of mechanically induced ischemia, alteplase can exacerbate ischemic damage. We have systematically reviewed the literature of both rtPA and L-arginine administration in mechanical focal ischemia. The rtPA worsens ischemic damage under certain conditions, whereas L-arginine can have both beneficial and deleterious effects dependent on the time of administration. The interaction between rtPA and L-arginine may be leading to the production of nitric oxide, which can cause direct neurotoxicity, altered cerebral blood flow, and disruption of the neurovascular unit. We suggest that alternative formulations of rtPA, in the absence of L-arginine, would provide new insight into rtPA neurotoxicity, and have the potential to offer more efficacious thrombolytic therapy for ischemic stroke patients.
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PMID:The contribution of L-arginine to the neurotoxicity of recombinant tissue plasminogen activator following cerebral ischemia: a review of rtPA neurotoxicity. 2073 61

Stroke is the third leading cause of death and the main cause of permanent disability in western countries. Reperfusion within 3 hours of symptoms-onset is the most beneficial of all therapeutic strategies for acute ischemic stroke. Alteplase has been the first thrombolytic treatment approved by FDA. However, its use is still limited to specific patient subgroups and may be complicated by severe side effects, including massive cerebral hemorrhages. This review is aimed at investigating the current and future treatment strategies in ischemic stroke, including new fibrinolytic drugs, sonothrombolysis, mechanical clot retrievals, and recent patents.
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PMID:Thrombolysis in ischemic stroke: focus on new treatment strategies. 2204 4

Alteplase (recombinant tissue plasminogen activator) has been used in the treatment of acute ischemic stroke for 10 years. The application of this drug is considered safe and effective. However, alteplase is also associated with side effects. The author is reporting on an unusual side effect of angioedema that is triggered by alteplase. Angioedema occurs through alteplase according to this study at a frequency of 5.88% (95% confidence interval: 0.98% to 28.76%). In this case immunoglobulin G was slightly increased. The relative risk to get an angioedema compared between the two genders is elevated in men 3.3 (95% confidence interval: 0.15% to 71.90%; P = 0.4423), who were 3.3 times more likely to suffer than women. The use of angiotensin-converting-enzyme (ACE) inhibitors is considered a possible risk factor for the occurrence of angioedema with concomitant administration of tissue plasminogen activator. The angioedema may occur with use of alteplase at any time, so treatment with this drug must always be carried out in intensive care and doctors must be ready for intubation if necessary.
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PMID:Lingual angioedema with macroglossia during the treatment of acute ischemic stroke with alteplase. 2239 62


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