Published online before print January 9, 2003, doi: 10.1161/01.STR.0000051506.43212.8B
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(Stroke. 2003;34:464.)
© 2003 American Heart Association, Inc.
Original Contributions |
Are Some Patients Likely to Benefit From Recombinant Tissue-Type Plasminogen Activator for Acute Ischemic Stroke Even Beyond 3 Hours From Symptom Onset?
From the Division of Clinical Care Research, Tufts-New England Medical Center, Boston, Mass.
Correspondence to David M. Kent, MD, MS, Division of Clinical Care Research, Tufts-New England Medical Center, 750 Washington St, NEMC No. 63, Boston, MA 02111. 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.
Key Words: intracerebral hemorrhage • risk assessment • stroke, acute • stroke, ischemic • thrombolytic therapy • time factors
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