EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging...

Area of Science:

• Neuroimaging
• Stroke Medicine
• Thrombolytic Therapy

Background:

• The Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) investigated alteplase for acute ischemic stroke.
• Previous analysis underestimated mismatch volumes, leading to negative primary outcomes.
• Coregistration of MRI maps may improve mismatch assessment.

Purpose of the Study:

• To evaluate alteplase's efficacy in attenuating infarct growth using coregistered perfusion and diffusion MRI.
• To reassess the primary outcome with improved mismatch volume assessment.

Main Methods:

• Patients were classified with mismatch using coregistered perfusion and diffusion-weighted imaging (PWI/DWI) ratios and volumes.
• The primary outcome compared infarct growth in alteplase versus placebo groups with coregistered mismatch.

Main Results:

• Coregistration identified mismatch in 93% of patients, higher than standard volumetric methods (85%).
• Geometric mean infarct growth was significantly attenuated with alteplase (ratio 0.58, P=0.0459) compared to placebo.
• 45 patients received alteplase and 43 received placebo in the coregistered mismatch group.

Conclusions:

• Alteplase significantly attenuated infarct growth when mismatch was determined using coregistration techniques.
• These findings necessitate a phase III trial for alteplase in select stroke patients beyond 3 hours.
• Penumbra selection using advanced imaging is crucial for optimizing thrombolytic therapy.