on January 9, 2003
Published online before print January 9, 2003, doi: 10.1161/01.STR.0000051506.43212.8B
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 12, 2002
From the Division of Clinical Care Research, Tufts-New England Medical Center, Boston, Mass. * To whom correspondence should be addressed. E-mail: dkent1{at}lifespan.org.
Background and Purpose--Recombinant tissue plasminogen activator (rtPA) has been demonstrated to improve outcomes in acute ischemic stroke when delivered within 3 hours of symptom onset. However, the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS B) trial, in which patients were treated mostly between 3 and 5 hours after symptom onset, found no overall benefit from rtPA. We hypothesized that a subgroup of patients at low risk for thrombolysis-related intracranial hemorrhage, identifiable on the basis of pretreatment clinical variables, may benefit even when treated after 3 hours, despite the overall results of the trial. Methods--Using an independently derived multivariate model that predicts the risk of thrombolysis-related intracranial hemorrhage in patients receiving tPA for acute myocardial infarction (based on 6 easily obtainable clinical characteristics), we stratified patients in the ATLANTIS B trial into low-, intermediate-, and high-risk tertiles. We examined outcomes in the prespecified low-risk subgroup using a global test of significance across 4 outcome scales. Results--Despite having a similar average baseline stroke severity and median time to treatment (270 minutes), patients in the prespecified low-risk group (n=194) were significantly less likely to have a symptomatic intracranial hemorrhage than other patients in the trial (2.2% versus 9.2%, P=0.03). Although there was no treatment effect for rtPA in the overall trial, a consistent trend favoring rtPA therapy (a 5% to 12% absolute treatment benefit) was found across 4 different stroke scales in the prespecified low-risk group (P=0.10). The treatment-benefit-by-risk interaction was significant (P=0.03). Conclusions--Use of a multivariate index based on clinical variables is a promising approach to assist in the selection of patients with a favorable risk-benefit profile for thrombolytic therapy beyond 3 hours.
Accepted on September 4, 2002
Are Some Patients Likely to Benefit From Recombinant Tissue-Type Plasminogen Activator for Acute Ischemic Stroke Even Beyond 3 Hours From Symptom Onset?
David M. Kent MD, MS*;
Key words: intracerebral hemorrhage • risk assessment • stroke, acute • stroke, ischemic • thrombolytic therapy • time factors
This article has been cited by other articles:
 |
|
 |
|
  O. Y. Bang, J. L. Saver, J. R. Alger, S. H. Shah, B. H. Buck, S. Starkman, B. Ovbiagele, D. S. Liebeskind, and for the UCLA MRI Permeability Investigators Patterns and Predictors of Blood-Brain Barrier Permeability Derangements in Acute Ischemic Stroke Stroke, February 1, 2009; 40(2): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Vickers, E. Basch, and M. W. Kattan Against Diagnosis Ann Intern Med, August 5, 2008; 149(3): 200 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Kent and R. A. Hayward Limitations of Applying Summary Results of Clinical Trials to Individual Patients: The Need for Risk Stratification JAMA, September 12, 2007; 298(10): 1209 - 1212. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kent, H. P. Selker, R. Ruthazer, E. Bluhmki, and W. Hacke Can Multivariable Risk-Benefit Profiling Be Used to Select Treatment-Favorable Patients for Thrombolysis in Stroke in the 3- to 6-Hour Time Window? Stroke, December 1, 2006; 37(12): 2963 - 2969. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kent, H. P. Selker, R. Ruthazer, E. Bluhmki, and W. Hacke The Stroke-Thrombolytic Predictive Instrument: A Predictive Instrument for Intravenous Thrombolysis in Acute Ischemic Stroke Stroke, December 1, 2006; 37(12): 2957 - 2962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Dzialowski, M. D. Hill, S. B. Coutts, A. M. Demchuk, D. M. Kent, O. Wunderlich, and R. von Kummer Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis: Prognostic Value of the Alberta Stroke Program Early CT Score in ECASS II Stroke, April 1, 2006; 37(4): 973 - 978. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Choi, B. T. Bateman, S. Mangla, R. S. Marshall, S. Prabhakaran, J. Chong, J. P. Mohr, H. Mast, and J. Pile-Spellman Endovascular Recanalization Therapy in Acute Ischemic Stroke Stroke, February 1, 2006; 37(2): 419 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Hayward, D. M. Kent, S. Vijan, and T. P. Hofer Reporting Clinical Trial Results To Inform Providers, Payers, And Consumers Health Aff., November 1, 2005; 24(6): 1571 - 1581. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Kent, M. D. Hill, R. Ruthazer, S. B. Coutts, A. M. Demchuk, I. Dzialowski, O. Wunderlich, and R. von Kummer "Clinical-CT Mismatch" and the Response to Systemic Thrombolytic Therapy in Acute Ischemic Stroke Stroke, August 1, 2005; 36(8): 1695 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 California Acute Stroke Pilot Registry (CASPR) Inv Prioritizing interventions to improve rates of thrombolysis for ischemic stroke Neurology, February 22, 2005; 64(4): 654 - 659. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Sims, G. Rordorf, E. E. Smith, W. J. Koroshetz, M. H. Lev, F. Buonanno, and L. H. Schwamm Arterial Occlusion Revealed by CT Angiography Predicts NIH Stroke Score and Acute Outcomes after IV tPA Treatment AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 246 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Reynolds, H. J. Kirchick, J. R. Dahlen, J. M. Anderberg, P. H. McPherson, K. K. Nakamura, D. T. Laskowitz, G. E. Valkirs, and K. F. Buechler Early Biomarkers of Stroke Clin. Chem., October 1, 2003; 49(10): 1733 - 1739. [Abstract] [Full Text] [PDF]
|
|