Skip to main content
AAN.com
Articles
December 12, 2000

Early stroke treatment associated with better outcome
The NINDS rt-PA Stroke Study

December 12, 2000 issue
55 (11) 1649-1655

Abstract

Background: The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study showed a similar percentage of intracranial hemorrhage and good outcome in patients 3 months after stroke treatment given 0 to 90 minutes and 91 to 180 minutes after stroke onset. At 24 hours after stroke onset more patients treated 0 to 90 compared to 91 to 180 minutes after stroke onset had improved by four or more points on the NIH Stroke Scale (NIHSS). The authors performed further analyses to characterize the relationship of onset-to-treatment time (OTT) to outcome at 3 months, early improvement at 24 hours, and intracranial hemorrhage within 36 hours.
Methods: Univariate analyses identified potentially confounding variables associated with OTT that could mask an OTT–treatment interaction. Tests for OTT–treatment interactions adjusting for potential masking confounders were performed. An OTT–treatment interaction was considered significant if p ≤ 0.10, implying that treatment effectiveness was related to OTT.
Results: For 24-hour improvement, there were no masking confounders identified and there was an OTT–treatment interaction (p = 0.08). For 3-month favorable outcome, the NIHSS met criteria for a masking confounder. After adjusting for NIHSS as a covariate, an OTT–treatment interaction was detected (p = 0.09): the adjusted OR (95% CI) for a favorable 3-month outcome associated with recombinant tissue-type plasminogen activator (rt-PA) was 2.11 (1.33 to 3.35) in the 0 to 90 minute stratum and 1.69 (1.09 to 2.62) in the 91 to 180 minute stratum. In the group treated with rt-PA, after adjusting for baseline NIHSS, an effect of OTT on the occurrence of intracranial hemorrhage was not detected.
Conclusions: If the NINDS rt-PA Stroke Trial treatment protocol is followed, this analysis suggests that patients treated 0 to 90 minutes from stroke onset with rt-PA have an increased odds of improvement at 24 hours and favorable 3-month outcome compared to patients treated later than 90 minutes. No effect of OTT on intracranial hemorrhage was detected within the group treated with rt-PA, possibly due to low power.

Get full access to this article

View all available purchase options and get full access to this article.

References

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;333:1581–1587.
2.
Brott TG, Haley EC, Levy DE,et al.Urgent therapy for stroke I. Pilot study of tissue plasminogen activator administered within 90 minutes.Stroke . 1992;23:632–640.
3.
Haley EC Jr., Levy DE, Brott TG,et al.Urgent therapy for stroke II. Pilot study of tissue plasminogen activator administered within 90–180 minutes from onset.Stroke . 1992;23:641–645.
4.
Zivin JA, Lyden PD, DeGirolami U,et al.Tissue plasminogen activator. Reduction of neurologic damage after experimental embolic stroke.Arch Neurol . 1988;45:387–391.
5.
Zivin JA. Factors determining the therapeutic window for stroke.Neurology . 1998;50:599–603.
6.
Mahoney FI, Barthel DW. Functional evaluation: The Barthel Index.Maryland State Med J . 1965;February
7.
Van Sweiten JC, Koudstall PJ, Visser MC, Schouten HJA, van Ginn J. Interobserver agreement for the assessment of handicap in stroke patients.Stroke . 1987;19:604–607.
8.
Teasdale G, Knill–Jones R, Vander J. Observer variability in assessing impaired consciousness and coma.J Neurol Neurosurg Psychiatry . 1978;41:603–610.
9.
The American Nimodipine Study Group.Clinical Trial of Nimodipine in Acute Ischemic Stroke.Stroke . 1992;23:3–8.
10.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.Intracerebral hemorrhage after intravenous rt-PA therapy for ischemic stroke.Stroke . 1997;28:2109–2118.
11.
The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group.Generalized efficacy of rt-PA for acute stroke: subgroup analysis of the NINDS rt-PA stroke trial.Stroke . 1997;28:2119–2125.
12.
McNeil D. Epidemiological research methods. New York: John Wiley & Sons, 1977;349–381.
13.
Tilley BC, Marler J, Geller NL,et al.Use of a global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke rt-PA Trial.Stroke . 1996;27:2136–2142.
14.
Tilley BC, Lyden PD, Brott TG, Lu M, Levine SR, Welch KMA. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Total quality improvement method for reduction of delays between emergency department admission and treatment of acute ischemic stroke.Arch Neurol . 1997;54:1466–1474.
15.
Zivin JA, Fisher M, DeGirolami U, Hemenway CC, Stashak JA. Tissue plasminogen activator reduces neurological damage after cerebral embolism.Science . 1985;230:1289–1292.
16.
DelZoppo GJ, Poeck K, Pessin MS,et al.Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke.Ann Neurol . 1992;32:78–86.
17.
Seber GAF. Linear regression analysis. New York: John Wiley & Sons, 1977;349–381.
18.
Marler JR, Emr M, Jones P, eds. Proceedings of the National Symposium on Rapid Identification and Treatment of Acute Stroke. The National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, 1997. Available online at http:www.ninds.nih.gov (NINDS) and http:www.stroke-site.org (Brain Attack Coalition).
19.
The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study Group.A systems approach to immediate evaluation and management of hyperacute stroke. Experience at eight centers and implications for community practice and patient care.Stroke . 1997;28:1530–1540.

Information & Authors

Information

Published In

Neurology®
Volume 55Number 11December 12, 2000
Pages: 1649-1655
PubMed: 11113218

Publication History

Received: October 21, 1998
Accepted: August 24, 2000
Published in print: December 12, 2000
Published online: July 2, 2023

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

J.R. Marler, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
B.C. Tilley, PhD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
M. Lu, PhD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
T.G. Brott, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
P.C. Lyden, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
J.C. Grotta, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
J.P. Broderick, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
S.R. Levine, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
M.P. Frankel, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
S.H. Horowitz, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
E.C. Haley, Jr., MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
C.A. Lewandowski
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
T.P. Kwiatkowski, MD
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.
for the NINDS rt-PA Stroke Study Group
From the National Institute of Neurological Disorders and Stroke, Rockville, MD.

Notes

Address correspondence and reprint requests to Dr. John R. Marler, Associate Director for Clinical Trials, National Institute of Neurological Disorders and Stroke, Neuroscience Center, Room 2216, 6001 Executive Boulevard, Rockville, MD 20892.

Metrics & Citations

Metrics

Citation information is sourced from Crossref Cited-by service.

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Utility of Computed Tomography Angiography of the Head in the Management of the Blunt Trauma Patient with Intracranial Hemorrhage, Journal of Trauma and Acute Care Surgery, (2025).https://doi.org/10.1097/TA.0000000000004563
    Crossref
  2. Liability of Neurologists, Legal Medicine, (513-521.e3), (2025).https://doi.org/10.1016/B978-0-443-12128-9.00074-7
    Crossref
  3. Early identification of stroke through deep learning with multi-modal human speech and movement data, Neural Regeneration Research, 20, 1, (234-241), (2024).https://doi.org/10.4103/1673-5374.393103
    Crossref
  4. Data-Driven Stroke Classification Utilizing Electromyographic Muscle Features and Machine Learning Techniques, Applied Sciences, 14, 18, (8430), (2024).https://doi.org/10.3390/app14188430
    Crossref
  5. The diagnosis of intracranial artery stenosis in patients with stroke by transcranial Doppler ultrasound: A meta-analysis, Technology and Health Care, 32, 2, (639-649), (2024).https://doi.org/10.3233/THC-220844
    Crossref
  6. Stroke Thrombolysis, Neurology, 102, 7, (2024)./doi/10.1212/WNL.0000000000209253
    Abstract
  7. Machine Learning-Based Prediction of Stroke in Emergency Departments, Therapeutic Advances in Neurological Disorders, 17, (2024).https://doi.org/10.1177/17562864241239108
    Crossref
  8. Efficacy and Safety of Alteplase Combined with Urinarykallid for Intravenous Thrombolysis on Acute Cerebral Infarction, Neurochemical Journal, 18, 1, (226-232), (2024).https://doi.org/10.1134/S1819712424010203
    Crossref
  9. Treatment of Acute Ischemic Stroke, Handbook of Cerebrovascular Disease and Neurointerventional Technique, (447-534), (2024).https://doi.org/10.1007/978-3-031-45598-8_8
    Crossref
  10. A Prospective Multicenter Analysis of Mobile Stroke Unit Cost‐Effectiveness, Annals of Neurology, 97, 2, (209-221), (2024).https://doi.org/10.1002/ana.27105
    Crossref
  11. See more
Loading...

View Options

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

  • 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
  • 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
  • [email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Figures

Tables

Media

Share

Share

Share article link

Share