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In Reply We thank Dr Little for his interest in our article.1 Dr Little is correct in that “[t]he VISTA database does not sanction reanalysis of any trial data that will test treatment effects….” However, our observational study did not set out to reanalyze the efficacy of a given thrombolytic agent, but rather to assess the impact of thrombolytic agents administered as part of routine clinical practice in acute stroke trials of neuroprotective agents. We should also emphasize that our study should only be viewed as hypothesis generating. Indeed, the observation that older patients with more severe strokes gain more from intravenous thrombolysis treatment on an absolute scale simply leads to the conclusion that this group of patients may not necessarily have to be denied treatment just on the basis of age or stroke severity and that more study of intravenous thrombolysis use in elderly patients with severe strokes is needed. Finally, the lack of efficacy of intravenous thrombolysis in the SPAN-100–negative patients might have been because the nonrandomized assignment led to a residual treatment selection bias.
Ovbiagele B, Saposnik G. Risk Index and Thrombolytic Treatment in Acute Ischemic Stroke—Reply. JAMA Neurol. 2014;71(10):1326. doi:10.1001/jamaneurol.2014.2297