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Neurology 2000;55:1649-1655
© 2000 American Academy of Neurology
Articles

Early stroke treatment associated with better outcome

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

From the National Institute of Neurological Disorders and Stroke, Rockville, MD.

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.

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.




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G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal
Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest, September 1, 2004; 126(3_suppl): 483S - 512S.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
J. Fiehler, T. Kucinski, K. Knudsen, M. Rosenkranz, G. Thomalla, C. Weiller, J. Rother, and H. Zeumer
Are There Time-Dependent Differences in Diffusion and Perfusion Within the First 6 Hours After Stroke Onset?
Stroke, September 1, 2004; 35(9): 2099 - 2104.
[Abstract] [Full Text] [PDF]

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 RadiologyHome page
A. Rovira, P. Orellana, J. Alvarez-Sabin, J. F. Arenillas, X. Aymerich, E. Grive, C. Molina, and A. Rovira-Gols
Hyperacute Ischemic Stroke: Middle Cerebral Artery Susceptibility Sign at Echo-planar Gradient-Echo MR Imaging
Radiology, August 1, 2004; 232(2): 466 - 473.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
M. A. De Georgia, D. W. Krieger, A. Abou-Chebl, T. G. Devlin, M. Jauss, S. M. Davis, W. J. Koroshetz, G. Rordorf, and S. Warach
Cooling for Acute Ischemic Brain Damage (COOL AID): A feasibility trial of endovascular cooling
Neurology, July 27, 2004; 63(2): 312 - 317.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
S. Wang, H. Gross, S. B. Lee, C. Pardue, J. Waller, F. T. Nichols III, R. J. Adams, and D. C. Hess
Remote Evaluation of Acute Ischemic Stroke in Rural Community Hospitals in Georgia
Stroke, July 1, 2004; 35(7): 1763 - 1768.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
D. M. Kent, J. Hinchey, L. L. Price, S. R. Levine, and H. P. Selker
In Acute Ischemic Stroke, Are Asymptomatic Intracranial Hemorrhages Clinically Innocuous?
Stroke, May 1, 2004; 35(5): 1141 - 1146.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
B. S. Carter, J. D. Rabinov, R. Pfannl, and L. H. Schwamm
Case 5-2004 - A 57-Year-Old Man with Slurred Speech and Left Hemiparesis
N. Engl. J. Med., February 12, 2004; 350(7): 707 - 716.
[Full Text] [PDF]

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 StrokeHome page
J. Kennedy and A.M. Buchan
Acute Neurovascular Syndromes: Hurry Up, Please, It's Time1
Stroke, February 1, 2004; 35(2): 360 - 362.
[Full Text] [PDF]

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 StrokeHome page
A. V. Alexandrov, C. E. Hall, L. A. Labiche, A. W. Wojner, and J. C. Grotta
Ischemic Stunning of the Brain: Early Recanalization Without Immediate Clinical Improvement in Acute Ischemic Stroke
Stroke, February 1, 2004; 35(2): 449 - 452.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
D. L. Brown, K. C. Johnston, D. P. Wagner, and E. C. Haley Jr
Predicting Major Neurological Improvement With Intravenous Recombinant Tissue Plasminogen Activator Treatment of Stroke
Stroke, January 1, 2004; 35(1): 147 - 150.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
J. P. Broderick
William M. Feinberg Lecture: Stroke Therapy in the Year 2025: Burden, Breakthroughs, and Barriers to Progress
Stroke, January 1, 2004; 35(1): 205 - 211.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
Y. Chen, C. Ruetzler, S. Pandipati, M. Spatz, R. M. McCarron, K. Becker, and J. M. Hallenbeck
Mucosal tolerance to E-selectin provides cell-mediated protection against ischemic brain injury
PNAS, December 9, 2003; 100(25): 15107 - 15112.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
O. Camilo and L. B. Goldstein
Statewide Assessment of Hospital-Based Stroke Prevention and Treatment Services in North Carolina: Changes Over the Last 5 Years
Stroke, December 1, 2003; 34(12): 2945 - 2950.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
H.-C. Koennecke
Editorial Comment--Challenging the Concept of a Dynamic Penumbra in Acute Ischemic Stroke
Stroke, October 1, 2003; 34(10): 2434 - 2435.
[Full Text] [PDF]

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 PediatricsHome page
A. Kirton, J. H. Wong, J. Mah, B. C. Ross, J. Kennedy, K. Bell, and M. D. Hill
Successful Endovascular Therapy for Acute Basilar Thrombosis in an Adolescent
Pediatrics, September 1, 2003; 112 (3): e248 - e251.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
K. Butcher, M. Parsons, T. Baird, A. Barber, G. Donnan, P. Desmond, B. Tress, and S. Davis
Perfusion Thresholds in Acute Stroke Thrombolysis
Stroke, September 1, 2003; 34(9): 2159 - 2164.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
J. Grotta, R. von Kummer, S. Davis, and G. Donnan
NIHSS/EIC Mismatch Explains the >1/3 MCA Conundrum * Response * Response
Stroke, September 1, 2003; 34 (9): e148 - e149.
[Full Text] [PDF]

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 StrokeHome page
M. D. Hill, H. A. Rowley, F. Adler, M. Eliasziw, A. Furlan, R. T. Higashida, L. R. Wechsler, H. C. Roberts, W. P. Dillon, N. J. Fischbein, et al.
Selection of Acute Ischemic Stroke Patients for Intra-Arterial Thrombolysis With Pro-Urokinase by Using ASPECTS
Stroke, August 1, 2003; 34(8): 1925 - 1931.
[Abstract] [Full Text] [PDF]

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 NeurologyHome page
A. W. Hsia, H. S. Sachdev, J. Tomlinson, S. A. Hamilton, and D. C. Tong
Efficacy of IV tissue plasminogen activator in acute stroke: Does stroke subtype really matter?
Neurology, July 8, 2003; 61(1): 71 - 75.
[Abstract] [Full Text] [PDF]

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 J. Neurol. Neurosurg. PsychiatryHome page
D M Brown and S R Levine
Clinical radiologic correlations in acute stroke: is the signal intensity at the end of the tunnel getting brighter quicker?
J. Neurol. Neurosurg. Psychiatry, July 1, 2003; 74(7): 840 - 841.
[Full Text] [PDF]

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 CirculationHome page
J. C. Grotta
Adding to the Effectiveness of Intravenous Tissue Plasminogen Activator for Treating Acute Stroke
Circulation, June 10, 2003; 107(22): 2769 - 2770.
[Full Text] [PDF]

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 StrokeHome page
M. M. Rymer, D. Thurtchley, and D. Summers
Expanded Modes of Tissue Plasminogen Activator Delivery in a Comprehensive Stroke Center Increases Regional Acute Stroke Interventions
Stroke, June 1, 2003; 34 (6): e58 - e60.
[Abstract] [Full Text] [PDF]

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K. Fassbender, S. Walter, Y. Liu, F. Muehlhauser, A. Ragoschke, S. Kuehl, and O. Mielke
"Mobile Stroke Unit" for Hyperacute Stroke Treatment
Stroke, June 1, 2003; 34 (6): e44 - e44.
[Full Text] [PDF]

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 NeurologyHome page
C. S. Kidwell, T. Shephard, S. Tonn, B. Lawyer, M. Murdock, W. Koroshetz, M. Alberts, G. J. Hademenos, and J. L. Saver
Establishment of primary stroke centers: A survey of physician attitudes and hospital resources
Neurology, May 13, 2003; 60(9): 1452 - 1456.
[Abstract] [Full Text] [PDF]

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L. R. Wechsler, R. Roberts, A. J. Furlan, R. T. Higashida, W. Dillon, H. Roberts, H. A. Rowley, L. C. Pettigrew, A. S. Callahan III, A. Bruno, et al.
Factors Influencing Outcome and Treatment Effect in PROACT II
Stroke, May 1, 2003; 34(5): 1224 - 1229.
[Abstract] [Full Text] [PDF]

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 J. Neurol. Neurosurg. PsychiatryHome page
T W J Watson, J E Simon, and A M Buchan
Stroke care: the way forward
J. Neurol. Neurosurg. Psychiatry, April 1, 2003; 74(4): 411 - 412.
[Full Text] [PDF]

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H. P. Adams Jr, R. J. Adams, T. Brott, G. J. del Zoppo, A. Furlan, L. B. Goldstein, R. L. Grubb, R. Higashida, C. Kidwell, T. G. Kwiatkowski, et al.
Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association
Stroke, April 1, 2003; 34(4): 1056 - 1083.
[Full Text] [PDF]

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I. L. Katzan, T. W. Graber, A. J. Furlan, S. Sundararajan, C. A. Sila, G. Houser, and D. M. Landis
Cuyahoga County Operation Stroke Speed of Emergency Department Evaluation and Compliance With National Institutes of Neurological Disorders and Stroke Time Targets
Stroke, April 1, 2003; 34(4): 994 - 998.
[Abstract] [Full Text] [PDF]

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M. D. Hill, S. B. Coutts, J.H. W. Pexman, A. M. Demchuk, P. Schramm, P. D. Schellinger, J. B. Fiebach, W. Hacke, and K. Sartor
CTA Source Images in Acute Stroke
Stroke, April 1, 2003; 34(4): 835 - 837.
[Full Text] [PDF]

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M. Fisher and T. G. Brott
Emerging Therapies for Acute Ischemic Stroke: New Therapies on Trial
Stroke, February 1, 2003; 34(2): 359 - 361.
[Full Text] [PDF]

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 StrokeHome page
P. D. Schellinger, J. B. Fiebach, W. Hacke, and J. Rother
Imaging-Based Decision Making in Thrombolytic Therapy for Ischemic Stroke: Present Status
Stroke, February 1, 2003; 34(2): 575 - 583.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
D. L. Tirschwell, W.T. Longstreth Jr, K. J. Becker, R. E. Gammans Sr, L. A. Sabounjian, S. Hamilton, and L. B. Morgenstern
Shortening the NIH Stroke Scale for Use in the Prehospital Setting
Stroke, December 1, 2002; 33(12): 2801 - 2806.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
R. C. Lisboa, B. D. Jovanovic, and M. J. Alberts
Analysis of the Safety and Efficacy of Intra-Arterial Thrombolytic Therapy in Ischemic Stroke
Stroke, December 1, 2002; 33(12): 2866 - 2871.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
G. W. Albers, L. R. Caplan, J. D. Easton, P. B. Fayad, J.P. Mohr, J. L. Saver, D. G. Sherman, and the TIA Working Group
Transient Ischemic Attack -- Proposal for a New Definition
N. Engl. J. Med., November 21, 2002; 347(21): 1713 - 1716.
[Full Text] [PDF]

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 Am. J. Neuroradiol.Home page
A. A. Rabinstein, E. F. M. Wijdicks, and D. A. Nichols
Complete Recovery after Early Intraarterial Recombinant Tissue Plasminogen Activator Thrombolysis of Carotid T Occlusion
AJNR Am. J. Neuroradiol., October 1, 2002; 23(9): 1596 - 1599.
[Abstract] [Full Text] [PDF]

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 StrokeHome page
J. Rother, P.D. Schellinger, A. Gass, M. Siebler, A. Villringer, J.B. Fiebach, J. Fiehler, O. Jansen, T. Kucinski, V. Schoder, et al.
Effect of Intravenous Thrombolysis on MRI Parameters and Functional Outcome in Acute Stroke <6 Hours
Stroke, October 1, 2002; 33(10): 2438 - 2445.
[Abstract] [Full Text] [PDF]


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