Published online before print September 2, 2004, doi: 10.1161/01.STR.0000140891.70547.56
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2004;35:2418.)
© 2004 American Heart Association, Inc.
Special Report |
Findings From the Reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemic Stroke Treatment Trial
From the Department of Neurology (T.J.I.), Mayo Clinic Scottsdale, Ariz; the Division of Biostatistics (W.M.O., T.J.H.C.), Mayo Clinic Rochester, Minn; the National Board of Health and Welfare (K.A.), Stockholm, Sweden; the Department of Emergency Medicine (L.R.G.), New York University School of Medicine, New York; the Department of Biostatistics (V.S.H.), Emory University, Atlanta, Ga; and the Department of Biostatistics (T.A.L.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Md.
Correspondence to Dr Timothy Ingall, Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259. Email ingall.timothy{at}mayo.edu
Background and Purpose— Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee "to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial."
Methods— The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA.
Results— A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences.
Conclusions— These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.
Key Words: randomized controlled trials • stroke, acute • tissue plasminogen activator
This article has been cited by other articles:
 |
|
 |
|
  S. M. Davis and G. A. Donnan 4.5 Hours: The New Time Window for Tissue Plasminogen Activator in Stroke Stroke, June 1, 2009; 40(6): 2266 - 2267. [Full Text] [PDF]
|
|
|
|
|
|
P. Mandava and T. A. Kent A Method to Determine Stroke Trial Success Using Multidimensional Pooled Control Functions Stroke, May 1, 2009; 40(5): 1803 - 1810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L.E. Cipriano, M.L. Steinberg, G.S. Gazelle, and R.G. Gonzalez Comparing and Predicting the Costs and Outcomes of Patients with Major and Minor Stroke Using the Boston Acute Stroke Imaging Scale Neuroimaging Classification System AJNR Am. J. Neuroradiol., April 1, 2009; 30(4): 703 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Thrombolytic therapy with alteplase for ischaemic stroke DTB, February 1, 2009; 47(2): 14 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, J. An, D. K. Strickland, and M. Yepes The Low-Density Lipoprotein Receptor-Related Protein 1 Mediates Tissue-Type Plasminogen Activator-Induced Microglial Activation in the Ischemic Brain Am. J. Pathol., February 1, 2009; 174(2): 586 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Alberts, R. A. Felberg, L. R. Guterman, S. R. Levine, and for Writing Group 4 Atherosclerotic Peripheral Vascular Disease Symposium II: Stroke Intervention: State of the Art Circulation, December 16, 2008; 118(25): 2845 - 2851. [Full Text] [PDF]
|
|
|
|
|
|
A. M. Pancioli, J. Broderick, T. Brott, T. Tomsick, J. Khoury, J. Bean, G. del Zoppo, D. Kleindorfer, D. Woo, P. Khatri, et al. The Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke: The CLEAR Stroke Trial Stroke, December 1, 2008; 39(12): 3268 - 3276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Flaherty, J. Karlawish, J. C. Khoury, D. Kleindorfer, D. Woo, and J. P. Broderick How important is surrogate consent for stroke research? Neurology, November 11, 2008; 71(20): 1566 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Liang, R. Lew, and J. A. Zivin Review of Tissue Plasminogen Activator, Ischemic Stroke, and Potential Legal Issues Arch Neurol, November 1, 2008; 65(11): 1429 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Hertzberg, T. Ingall, W. O'Fallon, K. Asplund, L. Goldfrank, T. Louis, and T. Christianson Methods and processes for the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial Clinical Trials, August 1, 2008; 5(4): 308 - 315. [Abstract] [PDF]
|
|
|
|
|
|
L. R. Caplan Thrombolysis, Fluctuations, Trials, and Such Arch Neurol, August 1, 2008; 65(8): 1017 - 1019. [Full Text] [PDF]
|
|
|
|
 |
|
 G. W. Albers, P. Amarenco, J. D. Easton, R. L. Sacco, and P. Teal Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 630S - 669S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. McCormick, I. Reeves, T. Baird, I. Bone, and K. W. Muir Implementation of a stroke thrombolysis service within a tertiary neurosciences centre in the United Kingdom QJM, April 1, 2008; 101(4): 291 - 298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Chung, R R Camejo, and D Barnett Alteplase for the treatment of acute ischaemic stroke: NICE technology appraisal guidance Heart, December 1, 2007; 93(12): 1616 - 1618. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R I Lindley Commentary on NICE guidelines for alteplase for the treatment of acute ischaemic stroke Heart, December 1, 2007; 93(12): 1617 - 1618. [Full Text] [PDF]
|
|
|
|
|
|
S. I. Savitz, R. Lew, E. Bluhmki, W. Hacke, and M. Fisher Shift Analysis Versus Dichotomization of the Modified Rankin Scale Outcome Scores in the NINDS and ECASS-II Trials Stroke, December 1, 2007; 38(12): 3205 - 3212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.J. Dickinson Intracerebral haemorrhage revisited QJM, November 1, 2007; 100(11): 715 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Goldstein Acute Ischemic Stroke Treatment in 2007 Circulation, September 25, 2007; 116(13): 1504 - 1514. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dirks, L. W Niessen, P. J Koudstaal, C. L Franke, R. J van Oostenbrugge, D. W J Dippel, and the members of the Delphi panel on indications and Intravenous thrombolysis in acute ischaemic stroke: from trial exclusion criteria to clinical contraindications. An international Delphi study J. Neurol. Neurosurg. Psychiatry, July 1, 2007; 78(7): 685 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Saver and B. Yafeh Confirmation of tPA Treatment Effect by Baseline Severity-Adjusted End Point Reanalysis of the NINDS-tPA Stroke Trials Stroke, February 1, 2007; 38(2): 414 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Demaerschalk The Stroke-Thrombolytic Predictive Instrument Provides Valid Quantitative Estimates of Outcome Probabilities and Aids Clinical Decision-Making Stroke, December 1, 2006; 37(12): 2865 - 2866. [Full Text] [PDF]
|
|
|
|
|
|
K. Z. Bambauer, S. C. Johnston, D. E. Bambauer, and J. A. Zivin Nonstroke Treatment--Reply Arch Neurol, October 1, 2006; 63(10): 1506 - 1507. [Full Text] [PDF]
|
|
|
|
|
|
P C A J Vroomen, M Uyttenbogaart, G J Luijckv, A Shuaib, and M Muratoglu Misleading conclusions on rt-PA treatment in the very elderly * Authors' reply. J. Neurol. Neurosurg. Psychiatry, June 1, 2006; 77(6): 799 - 799. [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Thomas, L. H. Schwamm, and M. H. Lev Case records of the Massachusetts General Hospital. Case 16-2006. A 72-year-old woman admitted to the emergency department because of a sudden change in mental status. N. Engl. J. Med., May 25, 2006; 354(21): 2263 - 2271. [Full Text] [PDF]
|
|
|
|
|
|
Part 4: Adult Basic Life Support Circulation, December 13, 2005; 112(24_suppl): IV-19 - IV-34. [Full Text] [PDF]
|
|
|
|
|
|
Part 9: Adult Stroke Circulation, December 13, 2005; 112(24_suppl): IV-111 - IV-120. [Full Text] [PDF]
|
|
|
|
|
|
Part 9: Stroke Circulation, November 29, 2005; 112(22_suppl): III-110 - III-104. [Full Text] [PDF]
|
|
|
|
|
|
B. Ovbiagele and J. L. Saver The smoking-thrombolysis paradox and acute ischemic stroke Neurology, July 26, 2005; 65(2): 293 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Smith, T. J. Ingall, W. M. O'Fallon, T. J. Hengy Christianson, K. Asplund, L. R. Goldfrank, V. S. Hertzberg, and T. A. Louis NINDS Stroke Trial Data Reanalysis Leaves Issues Unresolved * Response: Stroke, March 1, 2005; 36(3): 529 - 530. [Full Text] [PDF]
|
|
|
|
|
|
M. Kaste Thrombolysis: What More Does It Take? Stroke, February 1, 2005; 36(2): 200 - 202. [Full Text] [PDF]
|
|
|
|
|
|
J. Mann, T. J. Ingall, W. M. O'Fallon, K. Asplund, L. R. Goldfrank, V. S. Hertzberg, T. A. Louis, and T. J. H. Christianson NINDS Reanalysis Committee's Reanalysis of the NINDS Trial * Response Stroke, February 1, 2005; 36(2): 230 - 231. [Full Text] [PDF]
|
|