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

The publication of the positive results of the National Institute of Neurological Disorders and Stroke (NINDS) trial of alteplase (a recombinant tissue plasminogen activator; rt-PA) for acute stroke patients in 1995 and its approval by the US Food and Drug Administration as well as the American Academy of Neurology and American Heart Association increased the interest and attention of the medical community in acute stroke treatment. However, the implication of this NINDS Stroke Study and other thrombolytic trials in clinical practice remains controversial and debated. Furthermore, the recent publication of the results from the European Cooperative Acute Stroke Study II (ECASS II) and Alteplase Thrombolysis of Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) studies will feed the controversy, since the results of these two studies are disappointing and do not confirm the positive results of the NINDS Stroke Study as expected by clinicians managing patients with acute stroke. The Standard Treatment with Alteplase to Reverse Stroke (STARS) and Cleveland studies, which involved a large number of community hospitals to assess the safety profile and the benefit of rt-PA thrombolysis for acute stroke patients in clinical practice, have shown controversial results. Consequently, the issue arises of which is the more reasonable position concerning thrombolysis by alteplase, which seems to work but has not been proven yet beyond reasonable doubt? The recent publication of the results from the Prolyse in Acute Cerebral Thromboembolism (PROACT II) study has shown that intra-arterial thrombolysis with prourokinase is a benefit treatment in stroke patients with a proven middle cerebral artery occlusion within 6 h of stroke onset. Numerous trials devoted to neuroprotection against acute ischemic stroke have been prematurely stopped because of safety concerns or poor risk-benefit ratios, but some new neuroprotective drugs seem promising and are being tested in ongoing studies. The third issue under study concerns the use of antithrombotic drugs in the acute phase of stroke, particularly the new potent platelet glycoprotein IIb/IIIa antagonists such as abciximab. In this paper, we have reviewed selected recent clinical trials focusing on recent advances in acute stroke therapy.
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PMID:Recent progress in drug treatment for acute ischemic stroke. 1124 3

Ischemic stroke trials have traditionally sought to limit the range of disease studied according to several dimensions based on clinical examination and CT scan results. It has been proposed that the optimal sample for stroke trials would include a positive imaging diagnosis of a pathology rationally linked to the drug's mechanisms of action and that this would improve the likelihood of positive results. This principle has been supported by the results of the Prolyse in Acute Cerebral Thromoembolism II (PROACT II) study. Whereas trials of iv thrombolysis between 3 and 6 hours after symptom onset in a general sample of patients were not positive, selection of a subgroup by angiography was an effective strategy in this time period for PROACT II. This study contradicted the hypothesis that treatment of stroke beyond 3 hours would not be successful. MRI with diffusion and perfusion has been an appealing imaging modality because it provides pretreatment angiography, perfusion, and lesion volume information during a brief, non-invasive assessment. Current literature supports the validity of MRI as a marker for clinical severity and clinical improvement. The diffusion-perfusion mismatch, the MRI marker for the ischemic penumbra, is a very strong predictor of lesion volume growth. Several acute trials in progress use a positive imaging diagnosis for the basis of selection. As the field of stroke clinical trials examines opportunities for improving trial design, positive imaging diagnoses in patient selection are likely to assume an increasingly useful role.
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PMID:New imaging strategies for patient selection for thrombolytic and neuroprotective therapies. 1155 55

Intra-arterial (IA) thrombolysis is an emerging treatment strategy for acute ischemic stroke. In IA thrombolysis, the cervicocephalic arterial tree is traversed with an endovascular microcatheter delivery system, the catheter port is positioned immediately within and adjacent to the offending thrombus, and fibrinolytic agents are infused directly into the clot. This delivery technique permits high concentrations of lytic agent to be applied to the clot while minimizing systemic exposure. Early open series suggested that IA thrombolysis achieves higher recanalization rates than i.v. thrombolysis. The first randomized Phase III trial of IA thrombolysis, the Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial, confirmed this promise, showing that IA therapy begun up to 6 hours after symptom onset was associated with higher recanalization rates and better clinical outcomes, with acceptable hemorrhage rates. MRI studies have provided striking imaging evidence of the potential beneficial effects of IA therapy, showing not only rescue of regions of diffusion-perfusion mismatch but also normalization and salvage of some tissues with pretreatment bioenergetic failure evidenced by early diffusion abnormality. The Emergency Management of Stroke Bridging Trial demonstrated the feasibility of combined i.v. and intra-arterial thrombolysis. Intra-arterial thrombolysis is a promising treatment strategy for acute ischemic stroke. In coming years, IA thrombolysis, alone or in combination with endovascular mechanical reperfusion techniques, is likely to be increasingly refined and validated and to become a widely accepted therapy for acute ischemic stroke.
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PMID:Intra-arterial thrombolysis. 1155 57

In 1995, a two-part randomized trial showed the efficacy of intravenous tissue plasminogen activator (tPA) when given within 3 hours of onset of symptoms of acute ischemic stroke. Two subsequent trials were unable to extend the therapeutic window of intravenous tPA beyond 3 hours. A phase IV study performed by experienced stroke centers showed an acceptably low symptomatic intracerebral hemorrhage rate for intravenous tPA of only 3%, whereas a review of the Cleveland area experience showed a disturbingly high rate of symptomatic intracerebral hemorrhage of 15.7%. The Prolyse in Acute Cerebral Thromboembolism (PROACT) II study showed efficacy of intra-arterial pro-urokinase and intravenous heparin over intravenous heparin alone when given within 6 hours of onset of symptoms to patients with thrombotic occlusion of the proximal middle cerebral artery. Additional controlled investigations of intra-arterial thrombolytic therapy are needed. Neuroprotectants in combination with intravenous tPA have yet to show improved efficacy over the use of tPA alone.
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PMID:New insights on thrombolytic treatment of acute ischemic stroke. 1189 96

New MR imaging methods provide us with a hitherto unimaginable wealth of information on the pathophysiologic mechanisms operative in acute stroke. The only evidence-based acute stroke therapy, thrombolysis with IV tPA, only requires a CT to exclude brain hemorrhage before treatment. In PROACT 2 (Prolyse in Acute Cerebral Thromboembolism) locoregional thrombolysis with prourokinase improved the frequency of independent outcome. The only imaging methods used in this trial were a brain CT to exclude patients with brain hemorrhage and extended early infarct signs and a classical angiogram to demonstrate the presence of an M1 or M2 segment occlusions. In principle these therapies can be applied without using sophisticated MR or CT techniques. In this brief review we discuss the potential role of these novel techniques before application of intravenous or intraarterial thrombolysis.
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PMID:Imaging strategy for acute stroke therapy. 1474 1