Response to Letter Regarding Article, “Predicting Clinical Outcomes After Thrombolysis Using the iScore: Results From the Virtual International Stroke Trials Archive”
We thank Drs Rangaraju and Jadhav for their interest and positive comments on our article.1 They suggest that a modified Rankin Scale of 0 to 3 at 3 months may be an acceptable outcome after tissue-type plasminogen activator (tPA) for patients with stroke with an expected poor prognosis (as identified by an iScore≥200). Drs Rangaraju and Jadhav offered some estimation for an acceptable outcome and death at 3 months in favor of tPA. However, it is important to recognize that these estimations are not adjusted for significant differences in baseline characteristics, for example, age, baseline National Institutes of Health Stroke Scale, and onset to treatment, between tPA and untreated patients as illustrated in the original publication and in the online-only Data Supplement.1
As we showed, when applying the iScore to the Virtual International Stroke Trials Archive (VISTA) data set, there was a consistent benefit with tPA for patients with an expected good prognosis (iScore<200) across all outcome measures.1 However, no significant benefit with tPA was identified for patients with an iScore≥200 (which represented 10% of the entire cohort). In the VISTA cohort, we also found that tPA might decrease the risk of the composite catastrophic outcome—defined as severe disability or death (modified Rankin Scale, 4–6)—among patients with an iScore≥200. This could be because of the higher probability of reaching significance when a substantially larger number of patients achieve an outcome (ceiling effect). Consequently, it is difficult to be certain of the effect of tPA in this subgroup of patients (iScore≥200) with an expected poor outcome. Interestingly, previous studies applying the iScore to other data sets showed consistent results: patients with an iScore≥200 did not achieve better outcomes with tPA.2,3
For example, among patients with an iScore≥200 in the NINDS trials, tPA was not associated with a reduction in the risk of a catastrophic outcome (or regaining independency) at 3 months (tPA 70.7% versus placebo 76.9%; odds ratio, 0.73 [95% confidence interval, 0.31–1.68]) or at 1 year (tPA 77.4 versus placebo 78.4; odds ratio, 0.94 [95% confidence interval, 0.39–2.31]).3 The risk of symptomatic intracerebral hemorrhage was >4.5× higher among patients receiving tPA compared with placebo within the iScore≥200 strata.3
As suggested by Drs Rangaraju and Jadhav, this information may be used when counseling patients and their families. However, it is important to avoid generating false expectations. Perhaps, it would be useful to highlight that this group of patients, for example, those with an iScore≥200, (1) has an expected poor outcome irrespective of tPA treatment; (2) may not gain a significant benefit from tPA in terms of independency at 3 months (defined as a modified Rankin Scale, 0–2), but (3) may benefit from a decreased probability of a catastrophic outcome (defined as modified Rankin Scale, 4–6); and (4) is at significantly higher risk of symptomatic intracerebral hemorrhage (accounted in the analyzed outcomes).
At the present time, it is not clear whether a more or less aggressive intervention may help this group of patients to achieve better than expected outcomes.
Gustavo Saposnik, MD, MSc, FRCPC, FAHA
Stroke Outcomes Research Unit, Division of Neurology
Department of Medicine
St. Michael’s Hospital, University of Toronto
Toronto, Ontario, Canada
S. Claiborne Johnston, MD, PhD, FAHA
Department of Neurology
Clinical and Translational Science Institute,
University of California, San Francisco
Bruce Ovbiagele, MD, FAHA
Department of Neurology
Medical University of South Carolina, Charleston
on behalf of the VISTA Collaboration
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- © 2013 American Heart Association, Inc.
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