Skip to main content Accessibility help
×
Home

Improved Outcomes in Stroke Thrombolysis with Pre-specified Imaging Criteria

  • Brian Silver (a1), Bart Demaerschalk (a1) (a2), José G. Merino (a1), Edward Wong (a1), Arturo Tamayo (a1), Ashok Devasenapathy (a3), Christina O'Callaghan (a1), Andrew Kertesz (a1) (a2), G. Bryan Young (a1) (a4), Allan J. Fox (a1) (a5), J. David Spence (a1) and Vladimir Hachinski (a1)...

Abstract:

Background:

A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication.

Methods:

Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study.

Results:

Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004).

Conclusions:

The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older age and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.

RÉSUMÉ: Introduction:

Une étude du NINDS effectuée en 1995 a démontré les bénéfices de l'administration intraveineuse de l'activateur du plasminogène tissulaire (tPA) en phase aiguë de l'accident vasculaire cérébral ischémique (AVCI). Le taux d'hémorragie intracrânienne symptomatique (HICS) dans l'étude NINDS était de 6.4%, ce qui peut décourager certains médecins d'utiliser ce médicament.

Méthodes:

Depuis le premier décembre 1998, les patients porteurs d'un AVCI à London, Ontario ont été traités selon les critères de l'étude NINDS avec une exception importante: ceux qui avaient une lésion impliquant plus d'un tiers du territoire de l'artère cérébrale moyenne reproduit par la neuro-imagerie ont été exclus du traitement. La méthode utilisée pour estimer le territoire impliqué porte l'acronyme ICE et avait une valeur kappa médiane de 0.80 parmi cinq médecins. Les résultats ont été comparés à ceux de l'étude NINDS.

Résultats:

30 patients ont été traités entre le premier décembre 1998 et le premier février 2000. Plus de patients de London ont été traités après 90 minutes (p<0.00001) et ils étaient en général plus âgés que ceux qui ont participé à l'étude NINDS. Aucun cas de HICS n'a été observé. Moins de patients sont décédés ou avaient une invalidité sévère à trois mois (p=0.04) par rapport aux patients du bras avec traitement dans l'étude NINDS. Plus de patients ont eu une récupération partielle à 24 heures (p=0.02), plus de patients ont eu une récupération complète (p=0.03) et il y a eu moins de décès ou d'invalidité sévère à trois mois (p=0.004) par rapport aux patients à qui on avait administré le placebo dans l'étude.

Conclusions:

Les résultats de l'étude NINDS ont été reproduits et même améliorés dans certains cas, dans cette série de patients Canadiens, malgré l'âge plus avancé des patients et un traitement plus tardif. Ces observations suggèrent que des critères d'exclusion neuroradiologiques peuvent optimiser les bénéfices du traitement par le tPA.

    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Improved Outcomes in Stroke Thrombolysis with Pre-specified Imaging Criteria
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Improved Outcomes in Stroke Thrombolysis with Pre-specified Imaging Criteria
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Improved Outcomes in Stroke Thrombolysis with Pre-specified Imaging Criteria
      Available formats
      ×

Copyright

Corresponding author

London Health Sciences Centre, Department of Clinical Neurological Sciences, 339 Windermere Road, Room 7GE-5, London, Ontario N6A 5A5, Canada

References

Hide All
1. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995; 333: 15811587.
2. 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: 10171025.
3. 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: 11451150.
4. Buchan, AM, Barber, PA, Newcommon, N, et al. Effectiveness of t-PA in acute ischemic stroke: outcome relates to appropriateness. Neurology 2000; 54: 679684.
5. 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: 1822.
6. Grond, M, Stenzel, C, Schmulling, S, et al. Early intravenous thrombolysis for acute ischemic stroke in a community-based approach. Stroke 1998; 29: 15441549.
7. 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: 11511158.
8. Von Kummer, R, Allen, KL, Holle, R, et al. Acute stroke: usefulness of early CT findings before thrombolytic therapy. Radiology 1997; 205: 327333.
9. Hill, MD, Barber, PA, Buchan, AM, for the CASES Investigators. The Canadian Activase for Stroke Effectiveness Study (CASES). Stroke 2000; 31: 315. (Abstract)
10. 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. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282:20192026.
11. Deveikis, JP, Fox, AJ, Pelz, DM, Brothers, M, Drake, CG. “Disappearing infarcts”: signs of apparently reversible ischemic changes on serial CT and MR scans. AJNR Am J Neuroradiol 1988; 9: 1041. (Abstr)
12. 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; 282: 20032011.
13. //http:www.freetrip.com accessed on May 15, 2000
14. Epi Info, version 6.04b. Freeware downloaded from //http:www.cdc.gov/epo/epi/downepi6.htm on January 15, 2000
15. Hanley, JA, Lippman-Hand, A. If nothing goes wrong, is everything all right? Interpreting zero numerators. JAMA 1983; 249: 17431745.
16. Tanne, D, Bates, VE, Verro, P, et al. Initial clinical experience with IV tissue plasminogen activator for acute ischemic stroke: a multicenter survey. The t-PA Stroke Survey Group. Neurology 1999; 53: 424427.
17. Chapman, KM, Woolfenden, AR, Graeb, D, et al. Intravenous tissue plasminogen activator for acute ischemic stroke: a Canadian hospital’s experience. Stroke 2000; 31: 29202924.
18. Wang, DZ, Rose, JA, Honings, DS, Garwacki, DJ, Milbrandt, JC. Treating acute stroke patients with intravenous tPA. The OSF stroke network experience. Stroke 2000; 31: 7781.
19. Villar-Cordova, C, Morgenstern, LB, Barnholtz, JS, Frankowski, RF, Grotta, JC. Neurologists’ attitudes regarding rt-PA for acute ischemic stroke. Neurology 1998; 50: 14911494.
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: 12451251.
21. Thrombolytic therapy with streptokinase in acute ischemic stroke. The Multicenter Acute Stroke Trial – Europe Study Group. N Engl J Med 1996; 335: 145150.
22. 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: 961966.
23. Wang, YF, Tsirka, SE, Strickland, S, et al. Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med 1998; 4:228231.
24. Tsirka, SE, Rogove, AD, Bugge, TH, Degen, JL, Strickland, S. An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J Neurosci 1997; 17: 543552.
25. Klein, GM, Li, H, Sun, P, Buchan, AM. Tissue plasminogen activator does not increase neuronal damage in rat models of global and focal ischemia. Neurology 1999; 52: 13811384.
26. Meng, W, Wang, X, Asahi, M, et al. Effects of tissue type plasminogen activator in embolic versus mechanical models of focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1999; 19: 13161321.
27. Grotta, 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: 15281533.
28. Mitchell, EA, Scragg, R, Stewart, AW, et al. Results from the first year of the New Zealand cot death study. N Z Med J 1991; 104: 7176.
29. Davidson-Rada, J, Caldis, S, Tonkin, SL. New Zealand’s SIDS prevention program and reduction in infant mortality. Health Educ Q 1995; 22: 162171.

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed