Skip to main content
Log in

Optimal Timing of Thrombolytic Therapy in Acute Ischaemic Stroke

CNS Drugs Aims and scope Submit manuscript

Abstract

The clinical benefit of thrombolytic therapy for patients experiencing acute cerebral ischaemia has been demonstrated by both clinical trials and phase IV studies. However, such treatments must be initiated in a rapid manner, with treating physicians adhering to strict protocols designed to minimise delays and maximise safety. The efficacy of intravenous drug administration has been established with alteplase (recombinant tissue plasminogen activator; tPA) and ancrod, but only if these drugs can be administered within 3 hours of symptom onset. The use of alteplase beyond this timeframe, or outside of established protocols, may be hazardous. The use of alternative intravenous thrombolytic agents, such as streptokinase, also appears hazardous. Intra-arterial delivery of thrombolytic drugs such as pro-urokinase may extend clinical benefit to the 6-hour time frame.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I

Similar content being viewed by others

References

  1. Fletcher AP, Alkjaersig N, Lewis M, et al. A pilot study of urokinase therapy in cerebral infarction. Stroke 1976; 7(2): 135–42

    Article  PubMed  CAS  Google Scholar 

  2. Wardlaw JM, Warlow CP. Thrombolysis in acute ischemic stroke: does it work? Stroke 1992; 23(12): 1826–39

    Article  PubMed  CAS  Google Scholar 

  3. Mori E, Yoneda Y, Tabuchi M, et al. Intravenous recombinant tissue plasminogen activator in acute carotid artery territory ischemia. Neurology 1992; 42(5): 976–82

    Article  PubMed  CAS  Google Scholar 

  4. Haley Jr EC, Brott TG, Sheppard GL, et al. Pilot randomized trial of tissue plasminogen activator in acute ischemic stroke. The TPA Bridging Study Group. Stroke 1993; 24(7): 1000–4

    Google Scholar 

  5. del Zoppo GJ, Poeck K, Pessin MS, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 1992; 32(1): 78–86

    Article  PubMed  Google Scholar 

  6. Brott TG, Haley Jr EC, Levy DE, et al. Urgent therapy for stroke: part I. Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992; 23(5): 632–40

    CAS  Google Scholar 

  7. 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(13): 1017–25

    PubMed  CAS  Google Scholar 

  8. Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995 Dec 14; 333(24): 1581–7

    Article  Google Scholar 

  9. Hacke W, Bluhmki E, Steiner T, et al. Dichotomized efficacy end points and global end-point analysis applied to the ECASS intention-to-treat data set: post hoc analysis of ECASS I. Stroke 1998; 29(10): 2073–5

    Article  PubMed  CAS  Google Scholar 

  10. Steiner T, Bluhmki E, Kaste M, et al. The ECASS 3-hour cohort. Secondary analysis of ECASS data by time stratification. ECASS Study Group. European Cooperative Acute Stroke Study. Cerebrovasc Dis 1998 Jul–Aug; 8(4): 198–203

    CAS  Google Scholar 

  11. 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(9): 1145–50

    Article  PubMed  CAS  Google Scholar 

  12. Buchan AM, Barber PA, Newcommon N, et al. Effectiveness of t-PA in acute ischemic stroke: outcome relates to appropriateness. Neurology 2000; 54(3): 679–84

    Article  PubMed  CAS  Google Scholar 

  13. 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(1): 18–22

    Article  PubMed  CAS  Google Scholar 

  14. Grond M, Stenzel C, Schmulling S, et al. Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke 1998; 29(8): 1544–9

    Article  PubMed  CAS  Google Scholar 

  15. Wang DZ, Rose JA, Honings DS, et al. Treating acute stroke patients with intravenous tPA. The OSF Stroke Network experience. Stroke 2000; 31(1): 77–81

    CAS  Google Scholar 

  16. 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(9): 1151–8

    Article  PubMed  CAS  Google Scholar 

  17. Clark WM, Wissman S, Albers GW, et al. Recombinant tissuetype plasminogen activator (alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 Dec 1; 282(21): 2019–26

    CAS  Google Scholar 

  18. Clark WM, Albers GW, Madden KP, et al. The rtPA (alteplase) 0- to 6-hour acute stroke trial, part A (A0276g): results of a double-blind, placebo-controlled, multicenter study. Thrombolytic therapy in acute ischemic stroke study investigators. Stroke 2000; 31(4): 811–6

    CAS  Google Scholar 

  19. Albers GW, Clark WM, Madden KP, et al. The ATLANTIS t-PA acute stroke trial: results forpatients treated within three hours of stroke onset. Stroke 2000; 33(2): 493–6

    Article  Google Scholar 

  20. 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). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998; 352(9136): 1245–51

    CAS  Google Scholar 

  21. Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial — Europe Study Group. N Engl J Med 1996 Jul 18; 335(3): 145–50

    Article  Google Scholar 

  22. Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial — Italy (MAST-I) Group. Lancet 1995 Dec 9; 346(8989): 1509–14

    Google Scholar 

  23. 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(12): 961–6

    Article  PubMed  CAS  Google Scholar 

  24. Furlan A, Higashida R, Wechsler L, et al. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA 1999 Dec 1; 282(21): 2003–11

    CAS  Google Scholar 

  25. Sherman DG, Atkinson RP, Chippendale T, et al. Intravenous ancrod for treatment of acute ischemic stroke: the STAT study: a randomized controlled trial. Stroke Treatment with Ancrod Trial. JAMA 2000 May 10; 283(18): 2395–403

    CAS  Google Scholar 

  26. Madden KP. Thrombolytic therapy for stroke. Marshfield Clin J 2001; 2: 39–52

    Google Scholar 

Download references

Acknowledgements

No sources of funding were used in the preparation of this manuscript and the author has no financial relationships that are directly relevant to the contents of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ken Madden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Madden, K. Optimal Timing of Thrombolytic Therapy in Acute Ischaemic Stroke. Mol Diag Ther 16, 213–218 (2002). https://doi.org/10.2165/00023210-200216040-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00023210-200216040-00001

Keywords

Navigation