Neurocritical Care

, Volume 6, Issue 3, pp 181–185 | Cite as

Safety outcomes of Alteplase among acute ischemic stroke patients with special characteristics

  • P. N. Sylaja
  • Wei Dong
  • James C. Grotta
  • Mary K. Miller
  • Kristen Tomita
  • Scott Hamilton
  • Charles Semba
  • Michael D. Hill
Original Paper



Although tissue plasminogen activator (tPA) has been approved for use in acute ischemic stroke, concerns linger regarding its safety. We analyzed whether patients in special subgroups (i.e., age >70 years, baseline National Institute of Health Stroke Scale (NIHSS) score >20, diabetes, congestive heart failure (CHF), and of Hispanic origin) have a higher risk of symptomatic intracerebral hemorrhage (SICH) than patients without these characteristics.


Four prospective observational studies of acute ischemic stroke patients treated within 3 h with Alteplase were identified and individual patient data were pooled for this analysis. These included the Standard Treatment with Alteplase to Reverse Stroke Study [STARS, N = 389], Epidemiology Study of Ischemic Stroke [ESIS, N = 236], University Of Texas Houston Stroke Study [UT, N = 241], and Canadian Activase For Stroke Effectiveness Study [CASES, N = 1100]. The risk of SICH was calculated for all patients and for each of five subgroups.


A total of 1966 patients were studied. Overall the risk of symptomatic ICH was 4.7% (95%CI, 3.8–5.8%) and the risk was similar among patients with and without each of the five characteristics. Patients with advanced age, baseline NIHSS score >20, CHF or diabetes had increased mortality and significantly lower rate of functional recovery.


The present study suggests that these specified subgroups of patients are not at increased risk of SICH after stroke thrombolysis compared to those without these characteristics.


Thrombolysis Tissue plasminogen activator Acute ischemic stroke 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Graham GD. Tissue plasminogen activator for acute ischemic stroke in clinical practice. A meta-analysis of safety data. Stroke 2003;34:2847–50.PubMedCrossRefGoogle Scholar
  2. 2.
    NINDS rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–7.CrossRefGoogle Scholar
  3. 3.
    Larrue V, von Kummer R, del Zoppo G, Bluhmki T. Hemorrhagic transformation in acute ischemic stroke: potential contributing factors in the European Cooperative Acute Stroke Study. Stroke 1997;28:957–60.PubMedGoogle Scholar
  4. 4.
    The NINDS t-PA Stroke Study Group. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 1997;28:2109–18.Google Scholar
  5. 5.
    Larrue V, von Kummer R, Muller A, Bluhmki E. Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study. Stroke 2001;32:438–41.PubMedGoogle Scholar
  6. 6.
    Hill MD, Buchan AM, for the Canadian Alteplase for Stroke Effectiveness Study (CASES) Investigators. Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study. CMAJ 2005;172:1307–12.Google Scholar
  7. 7.
    Okada Y, Yamaguchi T, Minematsu K, Miyashita T, Sawada T, Sadoshima S et␣al. Hemorrhagic transformation in cerebral embolic stroke. Stroke 1989;20:589–603.Google Scholar
  8. 8.
    Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M et␣al. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator for acute ischemic stroke in clinical practice: the Multicenter rt-PA Acute Stroke Survey. Circulation 2002;105:1679–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Gurwitz JH, Gore JM, Gold berg RJ, Barron HV, Breen T, Rundle AC et␣al. Risk for intracranial hemorrhage after tissue plasminogen activator treatment for acute myocardial infarction: participants in the national registry of myocardial infarction 2. Ann Intern Med 1998;129:597–604.PubMedGoogle Scholar
  10. 10.
    Tanne D, Gorman MJ, Bates VE, Kasner SE, Scott P, Verro P et␣al. The tPA Stroke Survey Group. Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older. The tPA Stroke Survey experience. Stroke 2000;31:370–5.PubMedGoogle Scholar
  11. 11.
    Berrouschot J, Röther J, Glahn J, Kucinski T, Fiehler J, Thomalla G. Outcome and severe hemorrhagic complications of intravenous thrombolysis with tissue plasminogen activator in very old (≥80 years) stroke patients. Stroke 2005;36:2421–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Sylaja PN, Cote R, Buchan AM, Hill MD. Thrombolysis for acute ischemic stroke patients aged 80 years and older: Canadian Alteplase for stroke effectiveness study. J Neurol Neurosurg Psychiatry 2006;77:826–29.PubMedCrossRefGoogle Scholar
  13. 13.
    Heuschmann PU, Kolominsky-Rabas PL, Roether J, Misselwitz B, Lowitzsch K, Heidrich J et␣al. Predictors of in-hospital mortality in patients with acute ischemic stroke treated with thrombolytic therapy. JAMA 2004;292:1831–1838.PubMedCrossRefGoogle Scholar
  14. 14.
    Demchuk AM, Morgenstern LB, Krieger DW, Linda Chi T, Hu W, Wein TH et␣al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999;30:34–39.PubMedGoogle Scholar
  15. 15.
    Kase CS, Furlan AJ, Wechsler LR, Higashida RT, Rowley HA, Hart RG et␣al. and PROACT II investigators. Cerebral hemorrhage after intra-arterial thrombolysis for ischemic stroke. the PROACT II trial. Neurology 2001;57:1603–10.Google Scholar
  16. 16.
    Katzan IL, Furlan AJ, Lloyd LE, Frank JI, Harper DL, Hinchey JA et␣al. Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. JAMA 2000;283:1151–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Stansbury JP, Huanguang J, Williams LS, Vogel WB, Duncan PW. Ethnic disparities in stroke: epidemiology,acute care and postacute outcomes. Stroke 2005;36:374–87.PubMedCrossRefGoogle Scholar
  18. 18.
    Frey JL, Jahnke HK, Bulfinch EW. Differences in stroke between white, Hispanic, and Native American patients. the Barrow Neurological Institute stroke database. Stroke 1998;29:29–33.PubMedGoogle Scholar
  19. 19.
    Trouillas P, Nighoghossian N, Derex L, Adeleine P, Honnorat J, Neuschwander P et␣al. Thrombolysis with intravenous rtPA in a series of 100 cases of acute carotid territory stroke: determination of etiological,topographic,and radiological outcome factors. Stroke 1998;29:2529–40.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • P. N. Sylaja
    • 1
  • Wei Dong
    • 2
  • James C. Grotta
    • 3
  • Mary K. Miller
    • 2
  • Kristen Tomita
    • 2
  • Scott Hamilton
    • 4
  • Charles Semba
    • 2
  • Michael D. Hill
    • 1
  1. 1.Calgary Stroke Program, Department of Clinical Neurosciences, Foot hills Medical Center, Foot hills Hospital, Room 1242AUniversity of CalgaryCalgaryCanada
  2. 2.Genentech Inc.South San FranciscoUSA
  3. 3.Stroke Program, Department of NeurologyUniversity of Texas Health Sciences CenterHoustonUSA
  4. 4.Stanford University Department of NeurologyStanfordUSA

Personalised recommendations