Assessing Response to Stroke Thrombolysis

Abstract

Infarct growth can be used as a surrogate marker for clinical outcome in ischemic stroke trials.^1,2 This provides a meaningful intermediary between preclinical studies, where drug effects are often assessed on the basis of infarct volume attenuation, and phase 3 clinical outcomes. In the Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution (DEFUSE) study and the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET), recanalization and reperfusion have been demonstrated to significantly reduce infarct growth.^2,3 Although thrombolysis did not significantly attenuate infarct growth in the primary EPITHET analysis, subsequent analysis using more stringent optimized perfusion thresholds developed in positron emission tomography⁴ and magnetic resonance imaging^5,6 has demonstrated reduced growth in patients who received thrombolysis.⁷ Traditionally, stroke trial clinical end points are assessed at 90 days following stroke. There has been less consensus around the timing of imaging outcome assessments. However, these have generally been delayed, eg, 30 days in the DEFUSE study¹ and 90 days in EPITHET.² However, these were arbitrary choices and have some distinct disadvantages. By days 30 to 90, significant atrophy of the infarcted region has taken place.^8-10 This leads to an underestimate of the infarct volume relative to the baseline brain topography.