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Thrombolytic therapy in acute ischemic stroke

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Opinion statement

The use of intravenous thrombolytic therapy for the treatment of patients with acute ischemic stroke is now approved in the United States, Canada, Germany, and the European Union. Guidelines published in 1996 from the American Heart Association and American Academy of Neurology committees recommended intravenous administration of recombinant tissue-plasminogen activator (rt-PA) (0.9 mg/kg; maximum of 90 mg) given in a 10% bolus, followed by an infusion lasting 60 minutes, to patients within 3 hours of onset of ischemic stroke. The recommendations stipulate that a computed tomography scan before the infusion should not show major infarction, mass effect, edema, or hemorrhage. Yet, only a small fraction of eligible patients (< 5%) have received rt-PA during the 7 years since its approval in the United States. Although effective, thrombolysis carries an important risk (5% to 10%) of brain hemorrhage and edema that can prove fatal. Many physicians and medical centers are not presently equipped or willing to give thrombolytic drugs for stroke treatment.

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References and Recommended Reading

  1. Adams HP, Brott TC, 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, 94:1167–1174.

    PubMed  Google Scholar 

  2. Practice advisory: thrombolytic therapy for acute ischemic stroke—summary statement. Quality Standards Subcommittee of the American Academy of Neurology [no authors listed]. Neurology 1996, 47:835–839.

  3. Schellinger PD, Fiebach JB, Hacke W, Rother J: Imaging-based decision making in thrombolytic therapy for ischemic stroke: present status. Stroke 2003, 34:575–583. The most upto-date description of modern brain and vascular imaging in acute stroke. Also shows how the results can be used to make decisions on thrombolysis.

    Article  PubMed  Google Scholar 

  4. Wintermark M, Reichhart M, Thiran J-P, et al.: Prognostic accuracy of cerebral blood flow measurement by perfusion computed tomography, at the time of emergency room admission, in acute stroke patients. Ann Neurol 2002, 51:417–432.

    Article  PubMed  Google Scholar 

  5. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke Study Group [no authors listed]. N Engl J Med 1995, 333:1581–1587.

  6. Pessin M, del Zoppo GJ, Furlan AJ: Thrombolytic treatment in acute stroke: review and update of selective topics. In Cerebrovascular Diseases. Nineteenth Princeton Stroke Conference. Edited by Moskowitz MA, Caplan LR. Boston: Butterworth-Heinemann; 1995:409–418.

    Google Scholar 

  7. Caplan LR: Treatment. In Caplan’s Stroke, A Clinical Approach, 3rd edn. Boston: Butterworth-Heinemann; 2000:115–161. Reviews stroke treatment and tabulates the results of thrombolysis in detail.

    Google Scholar 

  8. Wardlaw JM, Warlow CP, Counsell C: Systematic review of evidence on thrombolytic therapy for acute ischaemic stroke. Lancet 1997, 350:607–614.

    Article  PubMed  CAS  Google Scholar 

  9. 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, 274:1017–1025.

    Article  PubMed  CAS  Google Scholar 

  10. Hacke W, Kaste M, Fieschi C, et al.: Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Lancet 1998, 352:1245–1251.

    Article  PubMed  CAS  Google Scholar 

  11. Clark WM, Wissman S, Albers GW, et al.: Recombinant tissue-type plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS study: a randomized controlled trial. JAMA 1999, 282:2019–2026.

    Article  PubMed  CAS  Google Scholar 

  12. Donnan GA, Davis SM, Chambers BR, et al.: Streptokinase for acute ischemic stroke with relationship to time of administration. JAMA 1996, 276:961–966.

    Article  PubMed  CAS  Google Scholar 

  13. Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial—Europe Study Group [no authors listed]. N Engl J Med 1996, 335:145–150.

  14. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. The Multicenter Acute Stroke Trial—Italy (MAST-I) Group [no authors listed]. Lancet 1995, 346:1509–1514.

  15. Marler JR, Tilley BC, Lu M, et al.: Early stroke treatment associated with better outcome: the NINDS rt-PA Stroke Study. Neurology 2000, 55:1649–1655.

    PubMed  CAS  Google Scholar 

  16. Generalized efficacy of t-PA for acute stroke. Sub-group analysis of the NINDS t-PA Stroke Trial [no authors listed]. Stroke 1997, 28:2119–2125.

  17. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NINDS t-PA Stroke Study Group [no authors listed]. Stroke 1997, 28:2109–2118.

  18. Chiu D, Krieger D, Villar-Cordova C, et al.: Intravenous tissue plasminogen activator for acute ischemic stroke, feasibility, safety, and efficacy in the first year of clinical practice. Stroke 1998, 29:18–22.

    PubMed  CAS  Google Scholar 

  19. Grond M, Stenzel C, Schmulling S, et al.: Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke 1998, 29:1544–1549.

    PubMed  CAS  Google Scholar 

  20. Buchan AM, Barber PA, Newcommon N, et al.: Effectiveness of t-PA in acute ischemic stroke. Outcome relates to appropriateness. Neurology 2000, 54:679–684.

    PubMed  CAS  Google Scholar 

  21. Albers GW, Bates VE, Clark WM, et al.: Intravenous tissue-type plasminogen activator for treatment of acute stroke: The Standard Treatment with Alteplase to Reverse Stroke (STARS) study. JAMA 2000, 283:1145–1150.

    Article  PubMed  CAS  Google Scholar 

  22. Katzan IL, Furlan AJ, Lloyd LE, et al.: Use of tissue-type plasminogen activator for acute ischemic stroke: The Cleveland Area Experience. JAMA 2000, 283:1151–1158.

    Article  PubMed  CAS  Google Scholar 

  23. Wolpert SM, Bruckmann H, Greenlee R, et al.: Neuroradiology evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. AJNR Am J Neuroradiol 1993, 14:3–13.

    PubMed  CAS  Google Scholar 

  24. Nenci GG, Gresele P, Taramelli M, et al.: Thrombolytic therapy of for thromboembolism of vertebrobasilar artery. Angiology 1983, 34:561–571.

    PubMed  CAS  Google Scholar 

  25. del Zoppo GJ, Ferbert A, Otis S, et al.: Local intra-arterial fibrinolytic therapy in acute carotid territory stroke: a pilot study. Stroke 1988, 19:307–313.

    PubMed  Google Scholar 

  26. Hacke W, Zeumer H, Ferbert A, et al.: Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988, 19:1216–1222.

    PubMed  CAS  Google Scholar 

  27. Zeumer H, Freitag HJ, Zanella F, et al.: Local intra-arterial fibrinolytic therapy in patients with stroke: urokinase versus recombinant tissue plasminogen activator (rt-PA). Neuroradiology 1993, 35:159–162.

    Article  PubMed  CAS  Google Scholar 

  28. Nesbit GM, Clark WM, O’Neil OR, Barnwell SL: Intracranial intra-arterial thrombolysis facilitated by micro-catheter navigation through an occluded cervical internal carotid artery. J Neurosurg 1996, 84:387–392.

    Article  PubMed  CAS  Google Scholar 

  29. del Zoppo GJ, Higashida RT, Furlan AJ, et al.: PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke 1998, 29:4–11.

    PubMed  Google Scholar 

  30. Furlan A, Higashida R, Wechsler L, et al.: Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. JAMA 1999, 282:2003–2011.

    Article  PubMed  CAS  Google Scholar 

  31. Katzan IL, Masaryk TJ, Furlan AJ, et al.: Intra-arterial thrombolysis for perioperative stroke after open heart surgery. Neurology 1999, 52:1081–1084.

    PubMed  CAS  Google Scholar 

  32. Lewandowski CA, Frankel M, Tomsick TA, et al.: Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy for acute ischemic stroke. Emergency Management of Stroke (EMS) bridging trial. Stroke 1999, 30:2598–2605.

    PubMed  CAS  Google Scholar 

  33. Hacke W, Zeumer H, Ferbert A, et al.: Intra-arterial thrombolytic therapy improves outcome in patients with acute vertebrobasilar occlusive disease. Stroke 1988, 19:1216–1222.

    PubMed  CAS  Google Scholar 

  34. Brückmann H, Ferbert A, del Zoppo G, et al.: Acute basilar thrombosis: angiologic-clinical comparison and therapeutic implications. Acta Radiol 1987, 369(suppl):38–42.

    Google Scholar 

  35. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Part 7: the era of reperfusion: section 2: acute stroke. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation [no authors listed]. Circulation 2000, 102(8 suppl):I204–I216.

  36. Wallace RC, Furlan AJ, Moliterno DJ, et al.: Basilar artery rethrombosis: successful treatment with plate-let glycoprotein IIb/IIIa receptor inhibitor. Am J Neuroradiol 1997, 18:1257–1260.

    PubMed  CAS  Google Scholar 

  37. Abciximab in acute ischemic stroke: a randomized, double-blind, placebo-controlled, dose-escalation study. The Abciximab in Ischemic Stroke Investigators [no authors listed]. Stroke 2000, 31: 601–609.

  38. von Kummer R, Hacke W: Safety and efficacy of intravenous tissue plasminogen activator and heparin in acute middle cerebral artery stroke. Stroke 1992, 23:646–652.

    Google Scholar 

  39. Mori E, Yoneda Y, Tabuchi M, et al.: Intravenous recombinant tissue plasminogen activator in acute carotid artery territory stroke. Neurology 1992, 42:976–982.

    PubMed  CAS  Google Scholar 

  40. Levy DE, Brott TG, Haley EC, et al.: Factors related to intracranial hematoma formation in patients receiving tissue-type plasminogen activator for acute ischemic stroke. Stroke 1994, 25:291–297.

    PubMed  CAS  Google Scholar 

  41. Bozzao L, Angeloni U, Bastianello S, et al.: Early angio-graphic and CT findings in patients with hemorrhagic infarction in the distribution of the middle cerebral artery. AJNR Am J Neuroradiol 1991, 12:1115–1121.

    PubMed  CAS  Google Scholar 

  42. Sloan MA, Price TR, Petito CK, et al.: Clinical features and pathogenesis of intracerebral hemorrhage after rt-PA and heparin therapy for acute myocardial infarction: the Thrombolysis in Myocardial Infarction (TIMI) II pilot and randomized clinical trial combined experience. Neurology 1995, 45:649–658.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cleveland Clinic Foundation, 9500 Euclid Avenue, 44195-5001, Cleveland, OH, USA

    Anthony J. Furlan MD

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  1. Anthony J. Furlan MD
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  2. Irene L. Katzan MD, MS
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  3. Louis R. Caplan MD
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Furlan, A.J., Katzan, I.L. & Caplan, L.R. Thrombolytic therapy in acute ischemic stroke. Curr Treat Options Cardio Med 5, 171–180 (2003). https://doi.org/10.1007/s11936-003-0001-4

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