, Volume 13, Issue 2, pp 115–126

Thrombolytics in Acute Ischaemic Stroke

A Guide to Patient Selection and Optimum Use
Disease Management


Intravenously administered alteplase (recombinant tissue plasminogen activator; rtPA) is the only medical treatment that has been approved for the management of acute ischaemic stroke. Although rtPA has demonstrated efficacy in improving outcomes of patients with a wide range of neurological impairments, it cannot be given with impunity. Thrombolytic therapy is associated with a considerable risk of intracranial bleeding that is likely to be catastrophic. Careful selection of patients to treat and intensive ancillary care are the keys for successful administration of rtPA. An algorithm for selection is based on the interval from the onset of stroke, history of recent medical illnesses or use of medications, findings of the medical and neurological examinations and the results of laboratory and brain imaging studies. Because rtPA must be given within 3 hours of onset of stroke, most patients cannot be treated. Thus, additional therapies are needed for treatment of patients with acute ischaemic stroke.


  1. 1.
    Adams HP Jr, Brott TG, Crowell RM, et al. Guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Circulation 1994; 90: 1588–601PubMedCrossRefGoogle Scholar
  2. 2.
    Langhorne P, Williams BO, Gilchrist W, et al. Do stroke units save lives? Lancet 1993; 342: 395–8PubMedCrossRefGoogle Scholar
  3. 3.
    Heiss WD, Graf R. The ischemic penumbra. Curr Opin Neurol 1994; 7: 11–9PubMedCrossRefGoogle Scholar
  4. 4.
    Zivin JA. Neuroprotective therapies in stroke. Drugs 1997; 54Suppl. 3: 83–8PubMedCrossRefGoogle Scholar
  5. 5.
    Lees KR. Does neuroprotection improve stroke outcome? Lancet 1998; 351: 1447–8PubMedCrossRefGoogle Scholar
  6. 6.
    Kay R, Wong KS, Yu YL, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995; 333: 1588–93PubMedCrossRefGoogle Scholar
  7. 7.
    The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997; 349: 1569–81CrossRefGoogle Scholar
  8. 8.
    Publications Committee for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) Investigators. Low molecular weight heparinoid, ORG 10172 (danaparoid), and outcome after acute ischemic stroke: a randomized controlled trial. JAMA 1998; 279: 1265–72CrossRefGoogle Scholar
  9. 9.
    CAST (Chinese Acute Stroke Trial) Collaborative Group. CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. Lancet 1997; 349: 1641–9CrossRefGoogle Scholar
  10. 10.
    Ancrod Stroke Study Investigators. Ancrod for the treatment of acute ischemic brain infarction. Stroke 1994; 25: 1755–9CrossRefGoogle Scholar
  11. 11.
    Sherman DG, STAT Writers Group. Defibrinogenation with Viprinex (ancrod) for the treatment of acute ischemic stroke. Stroke 1999; 30: 234Google Scholar
  12. 12.
    Multicentre Acute Stroke Trial — Italy (MAST-I) Group. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet 1995; 346: 1509–14Google Scholar
  13. 13.
    Multicenter Acute Stroke Trial — Europe Study Group. Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med 1996; 335: 145–50CrossRefGoogle Scholar
  14. 14.
    Donnan GA, Davis SM, Chambers BR, et al. Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. JAMA 1996; 276: 961–6PubMedCrossRefGoogle Scholar
  15. 15.
    del Zoppo GJ, Higashida RT, Furlan AJ, et al., PROACT Investigators. PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Prolyse in Acute Cerebral Thromboembolism. Stroke 1998; 29: 4–11PubMedCrossRefGoogle Scholar
  16. 16.
    Furlan AJ, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischaemic stroke. The PROACT II Study: a randomized controlled trial. JAMA 1999; 282: 2003–11PubMedCrossRefGoogle Scholar
  17. 17.
    Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274: 1017–25PubMedCrossRefGoogle Scholar
  18. 18.
    National Institute of Neurological Disorders and Stroke rtPA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 1581–7CrossRefGoogle Scholar
  19. 19.
    Hacke W, Kaste M, Fieschi C, et al., Second European-Australasian Acute Stroke Study Investigators. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998; 352: 1245–51PubMedCrossRefGoogle Scholar
  20. 20.
    Clark WM, Wissman S, Albers GW, et al., ATLANTIS Stroke Study Investigators. Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282: 2019–26PubMedCrossRefGoogle Scholar
  21. 21.
    Adams HP Jr, Brott TG, Furlan AJ, et al. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Circulation 1996; 94: 1167–74PubMedCrossRefGoogle Scholar
  22. 22.
    Norris JW, Buchan A, Cote R, et al. Canadian guidelines for intravenous thrombolytic treatment in acute stroke. A consensus statement of the Canadian Stroke Consortium. Can J Neurol Sci 1998; 25: 259Google Scholar
  23. 23.
    Steiner T, Bluhmki E, Kaste M, et al. The ECASS 3-hour cohort. Cerebrovasc Dis 1998; 8: 198–203PubMedCrossRefGoogle Scholar
  24. 24.
    Hachinski V. Thrombolysis in stroke. Between the promise and the peril. JAMA 1996; 276: 995–6PubMedCrossRefGoogle Scholar
  25. 25.
    Kasner SE, Villar-Cordova CE, Tong D, et al. Hemopericardium and cardiac tamponade after thrombolysis for acute ischemic stroke. Neural 1998; 50: 1859Google Scholar
  26. 26.
    NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 1997; 28: 2109–18CrossRefGoogle Scholar
  27. 27.
    Anonymous. Generalized efficacy of t-PA for acute stroke. Subgroup analysis of the NINDS t-PA Stroke Trial. Stroke 1997; 28: 2119–25Google Scholar
  28. 28.
    Brott T, Adams HP Jr, Olinger CP, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989; 20: 864–70PubMedCrossRefGoogle Scholar
  29. 29.
    Adams Jr HP, Davis PH, Leira EC, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke. Neurology 1999; 53: 126–31PubMedCrossRefGoogle Scholar
  30. 30.
    von Kummer R, Meyding-Lamade U, Forsting M, et al. Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR Am J Neuroradiol 1994; 15: 9–15Google Scholar
  31. 31.
    von Kummer R, Nolte PN, Schnittger H, et al. Detectability of cerebral hemisphere ischaemic infarcts by CT within 6 h of stroke. Neuroradiology 1996; 38: 31–3CrossRefGoogle Scholar
  32. 32.
    Schriger DL, Kalafut M, Starkman S, et al. Cranial computed tomography interpretation in acute stroke: physician accuracy in determining eligibility for thrombolytic therapy. JAMA 1998; 279: 1293–7PubMedCrossRefGoogle Scholar
  33. 33.
    Gratta JC, Chiu D, Lu M, et al. Agreement and variability in the interpretation of early CT changes in stroke patients qualifying for intravenous rtPA therapy. Stroke 1999; 30: 1528–33CrossRefGoogle Scholar
  34. 34.
    Levine SR, Gorman M. Telestroke. The application of telemedicine for stroke. Stroke 1999; 30: 464–9PubMedCrossRefGoogle Scholar
  35. 35.
    Adams Jr HP. Treating ischemic stroke as an emergency. Arch Neurol 1998; 55: 457–61PubMedCrossRefGoogle Scholar
  36. 36.
    Wang DZ, Rose JA, Honings DS, et al., for the OSF Stroke Team. Treating acute stroke patients with intravenous tPA. Stroke 2000; 31: 77–81PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Division of Cerebrovascular Diseases, Department of NeurologyUniversity of Iowa College of MedicineIowa CityUSA
  2. 2.Department of NeurologyUniversity of IowaIowa CityUSA

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