Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: Insights from the desmoteplase in acute stroke trials

Steven Warach, Yasir Al-Rawi, Anthony J. Furlan, Jochen B. Fiebach, Max Wintermark, Annika Lindstén, Jamal Smyej, David B. Bharucha, Salvador Pedraza, Howard A. Rowley

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

BACKGROUND AND PURPOSE-: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. METHODS-: In post hoc analyses we assessed the relationships of magnetic resonance imaging-measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. RESULTS-: In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points (P<0.0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16-6.94; P=0.023) for MMV >60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. CONCLUSIONS-: Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials.

Original languageEnglish (US)
Pages (from-to)2313-2318
Number of pages6
JournalStroke
Volume43
Issue number9
DOIs
StatePublished - Sep 1 2012

Keywords

  • acute cerebral infarction
  • desmoteplase
  • diffusion-weighted imaging
  • magnetic resonance imaging
  • mismatch
  • perfusion
  • stroke
  • thrombolysis

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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    Warach, S., Al-Rawi, Y., Furlan, A. J., Fiebach, J. B., Wintermark, M., Lindstén, A., Smyej, J., Bharucha, D. B., Pedraza, S., & Rowley, H. A. (2012). Refinement of the magnetic resonance diffusion-perfusion mismatch concept for thrombolytic patient selection: Insights from the desmoteplase in acute stroke trials. Stroke, 43(9), 2313-2318. https://doi.org/10.1161/STROKEAHA.111.642348