Stroke; a journal of cerebral circulation
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Review Meta Analysis
Systematic review of outcome after ischemic stroke due to anterior circulation occlusion treated with intravenous, intra-arterial, or combined intravenous+intra-arterial thrombolysis.
The optimal approach to recanalization in acute ischemic stroke is unknown. We performed a literature review and meta-analysis comparing the relative efficacy of 6 reperfusion strategies: (1) 0.9 mg/kg intravenous tissue-type plasminogen activator; (2) intra-arterial chemical thrombolysis; (3) intra-arterial mechanical thrombolysis; (4) intra-arterial combined chemical/mechanical thrombolysis; (5) 0.6 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis; and (6) 0.9 mg/kg intravenous tissue-type plasminogen activator and intra-arterial thrombolysis. ⋯ This study found no evidence that one reperfusion strategy is superior with respect to efficacy or safety, supporting clinical equipoise between reperfusion strategies. Intravenous tissue-type plasminogen activator remains the standard of care for acute ischemic stroke. Randomized clinical trials are necessary to determine the efficacy of alternative reperfusion strategies. Participation in such trials is strongly recommended.
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Randomized Controlled Trial
Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: insights from the desmoteplase in acute stroke trials.
The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. ⋯ Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.
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The effectiveness of prothrombin complex concentrate (PCC) products available in the United States that contain low levels of factor VII (3-factor PCC) has not been tested. The purpose of this study was to review our experience with 3-factor PCC (Profilnine) in the setting of warfarin-associated intracranial hemorrhage (wICH). ⋯ Reversal of coagulopathy in wICH with Profilnine was incomplete and associated with serious adverse events. In the absence of available 4-factor PCC, options for urgent reversal of anticoagulation in wICH remain limited.
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Tissue plasminogen activator (tPA) is the only approved therapy for acute ischemic stroke. However, tPA has a brief therapeutic window. Its side effects include intracerebral bleeding and neurotoxicity. Therefore, a combination therapy with tPA and agents that can extend the therapeutic window of tPA and/or counteract its side effects are warranted. Here, we studied whether 3K3A-APC, a neuroprotective analog of activated protein C with reduced anticoagulant activity, can enhance the therapeutic effects of tPA in models of ischemic stroke in rodents. ⋯ The 3K3A-APC extends the therapeutic window of tPA for ischemic stroke in rodents. Therefore, this combination therapy also should be considered for treating stroke in humans.