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Greater effect of stroke thrombolysis in the presence of arterial obstruction

Authors

  • Deidre A. De Silva MBBS, MRCP, FAMS,

    Corresponding author
    1. Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore
    • Department of Neurology, Singapore General Hospital, Outram Road, Singapore 169608
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  • Leonid Churilov PhD,

    1. Florey Neuroscience Institutes (National Stroke Research Institute), Melbourne, Australia
    2. Department of Mathematics and Statistics, University of Melbourne, Melbourne, Australia
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  • Jean-Marc Olivot MD, PhD,

    1. Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University Medical Center, Stanford, CA
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  • Soren Christensen MD, PhD,

    1. Department of Neurology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
    2. Department of Radiology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
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  • Maarten G. Lansberg MD, PhD,

    1. Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University Medical Center, Stanford, CA
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  • Michael Mlynash MD, MS,

    1. Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University Medical Center, Stanford, CA
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  • Bruce C.V. Campbell MBBS, BMedSc, FRACP,

    1. Department of Neurology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
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  • Patricia Desmond MSc, MD, FRANZCR,

    1. Department of Radiology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
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  • Matus Straka PhD,

    1. Department of Radiology, Stanford University School of Medicine, Stanford, CA
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  • Roland Bammer PhD,

    1. Department of Radiology, Stanford University School of Medicine, Stanford, CA
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  • Gregory W. Albers MD,

    1. Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University Medical Center, Stanford, CA
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  • Stephen M. Davis MD, FRACP,

    1. Department of Neurology, Royal Melbourne Hospital and University of Melbourne, Melbourne, Australia
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  • Geoffrey A. Donnan MD, FRACP,

    1. Florey Neuroscience Institutes (National Stroke Research Institute), Melbourne, Australia
    2. Austin Health, University of Melbourne, Melbourne, Australia
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  • on behalf of the EPITHET-DEFUSE Investigators

    1. Florey Neuroscience Institutes (National Stroke Research Institute), Melbourne, Australia
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  • Members of the EPITHET-DEFUSE Investigators are listed in the Appendix on page xx.

Abstract

Objective:

Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.

Methods:

We analyzed 175 ischemic stroke patients treated in the 3–6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).

Results:

Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1–50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, −3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21–43, p < 0.001).

Interpretation:

The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis. ANN NEUROL 2011;70:601–605

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