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  • Review Article
  • Published:

How to make better use of thrombolytic therapy in acute ischemic stroke

Abstract

Around 15 years have now elapsed since thrombolysis was first shown to be effective for treating acute ischemic stroke, but therapeutic uptake has been modest. As outlined in this Review, research efforts are being directed towards rectifying this situation in a number of ways. First, strategies to enhance thrombolytic efficacy are being tested; these include intravenous and intra-arterial bridging protocols, sonothrombolysis, and the use of alternative thrombolytic agents. Second, means of extending the 4.5-h therapeutic time window up to 6 h, or even up to 9 h in patients selected on the basis of imaging, are being investigated in clinical trials. Prolongation of the time window using neuroprotection to 'freeze' penumbral tissue is also being attempted. Third, attempts are underway to reduce the risk of symptomatic intracerebral hemorrhage (currently affecting about 7% of cases) by refining imaging selection criteria, and through the use of alternative thrombolytic agents, lower doses of tissue plasminogen activator, blood-based biomarkers, and neuroprotectants. Last, in an effort to include more people within the currently accepted therapeutic time window, improvements in prehospital management strategies are being introduced. Elimination of prehospital and in-hospital delays is an urgent priority.

Key Points

  • Administration of intravenous tissue plasminogen activator (tPA) 0–90 min after stroke onset approximately doubles the odds of near-complete recovery compared with administration at 3.0–4.5 h

  • Newer thrombolytic agents being tested in phase II and III clinical trials include desmoteplase and tenecteplase

  • Penumbral criteria to select patients with viable brain tissue up to 9 h after stroke onset are now being entered into trials of thrombolysis

  • Hypothermia in combination with tPA may be the most effective way to 'freeze' the ischemic penumbra and needs to be tested by clinical trial

  • Bridging protocols using combined intravenous and intra-arterial approaches with tPA may increase recanalization rates

  • An urgent need exists to increase therapeutic uptake of thrombolysis by use of public education campaigns, and by improving prehospital and in-hospital management

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Figure 1: Time to treatment and outcome.
Figure 2: NNT and time after stroke.
Figure 3: Freezing the ischemic penumbra: effect on infarct core growth.

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Bruce C. V. Campbell, Deidre A. De Silva, … Geoffrey A. Donnan

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G. A. Donnan, S. M. Davis and D. W. Howells all contributed substantially to researching data for the article, discussion of content, writing, and review and/or editing of the manuscript. M. W. Parsons and H. Ma contributed substantially to discussion of content, writing, and review and/or editing. H. Dewey reviewed the manuscript before submission.

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Correspondence to Geoffrey A. Donnan.

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Donnan, G., Davis, S., Parsons, M. et al. How to make better use of thrombolytic therapy in acute ischemic stroke. Nat Rev Neurol 7, 400–409 (2011). https://doi.org/10.1038/nrneurol.2011.89

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