Abstract 3849: The Optimal Target for Thrombolytic Trials: The Interaction of Mismatch Size and IV tPA Treatment in Predicting Good Clinical Outcome
Introduction: Because IV tPA treatment initiated within 4.5 hours is the only acute stroke therapy of proven clinical efficacy, this population offers the greatest validity for determining imaging markers that optimally would differentiate clinical outcomes in treated vs. placebo patients in later time-window clinical trials. The Perfusion Diffusion Mismatch (PDM) approximates the ischemic penumbra, but there is no consensus on the optimal definition or threshold to be used in trials. We assessed the relationship of mismatch size to clinical outcome of an IV tPA treated sample compared with an untreated cohort.
Methods: We selected patients from the NINDS Lesion Evolution of Stroke and Ischemia On Neuroimaging (LESION) database who met the following criteria: 1) treated with standard IV tPA 2) received multimodal MRI pre-treatment including diffusion (DWI) and perfusion imaging (PWI), 3) had interpretable MRI imaging showing 4) non-lacunar infarcts or lesions less than 100 ml volumes on DWI and 5) follow-up modified Rankin Score (mRS). We also selected 23 acute stroke patients who did not receive treatment but otherwise met the same criteria. Volumes were measured from the DWI and Mean Transit Time (MTT) images. PDM was defined as either a volume (MTT-DWI) or a percentage (MTT-DWI/MTT). Good outcome was defined as mRS of 0-1. Logistic regression was performed to predict good outcome with covariates of age, initial NIHSS, PDM size, tPA treatment, and tPA treatment by PDM size interaction.
Result: Ninety-six patients were treated with IV tPA, 23 patients had no treatment. The figures, showing the unadjusted proportions of patients achieving good outcome as a function of minimum PDM size, suggest greater separation of treated and untreated patients at larger PDM sizes. For percentage PDM a significant interaction of tPA treatment by PDM size was observed at ≥ 80% (p=0.029), indicating that the benefit of tPA treatment is greater for PDM ≥ 80%. For volume PDM, the interaction of tPA treatment by PDM size trended positive at ≥ 50 ml (p=0.058).
Conclusion: Greater differences in clinical outcomes with IV tPA versus untreated patients were evident with PDM ≥ 80% or ≥ 50 ml. These minimums of PDM size suggest an optimal target for thrombolytic trials.
- © 2012 by American Heart Association, Inc.