The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial – A post hoc analysis

Pfaff JAR, Bendszus M, Donnan G, Molina C, Leys D, Schellinger PD, Schwab S, Toni D, Wahlgren N, Hacke W, Ringleb PA (2020)

Publication Type: Journal article

Publication year: 2020


DOI: 10.1177/2396987320920114


Introduction: To investigate the impact of a mismatch between diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) on functional outcome in patients with acute stroke in a prolonged time window or unknown time of symptom onset randomized to intravenous thrombolysis or placebo. Patients and Methods: We performed a post-hoc analysis of the European Cooperative Acute Stroke Study-4 (ECASS-4) trial. ECASS-4 was an investigator driven, phase 3, multi-center, double-blind, placebo-controlled study which randomized ischemic stroke patients presenting within 4.5 and 9h of stroke onset or unknown time-window to either rt-PA or placebo after MR-imaging. Two subgroups “no mismatch” (nMM) and “any mismatch” (aMM) were created by applying a DWI-FLAIR-mismatch criterion. We calculated frequency of nMM and aMM and performed a univariate analysis (Fisher's Test) for excellent clinical outcome (mRS 0-1) and mortality (mRS=6). Results: MR-Imaging of n=111/119 (93.2%) patients was suitable for this analysis. DWI-FLAIR mismatch was found in 49 patients (44.1%). Proportions of mismatch nMM and aMM were comparable in treatment-groups (aMM: Placebo 46.3%, Alteplase 42.1%; p=0.70). Patients with nMM showed no benefit of rt-PA-treatment (OR (95%CI) mRS 0-1: 0.95 (0.29-3.17)). Patients with aMM showed a point estimate of the odds ratio in favour of a treatment benefit of rt-PA (mRS 0-1: OR (95%CI) 2.62 (0.68-11.1)). Mortality within 90 days was not different in patients treated with rt-PA if nMM (15.2%) or aMM (12.5%) was present. Discussion: In this analysis no significant evidence, but subtle indication towards patients treated with rt-PA in a prolonged time window reaching an excellent clinical outcome if a DWI-FLAIR-mismatch is present on initial stroke MR-imaging. Conclusion: A DWI-FLAIR mismatch in the region of ischemia as imaging based surrogate parameter for patient selection for i.v. rt-PA should be strongly pursued.

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Pfaff, J.A.R., Bendszus, M., Donnan, G., Molina, C., Leys, D., Schellinger, P.D.,... Ringleb, P.A. (2020). The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial – A post hoc analysis. European Stroke Journal.


Pfaff, Johannes A. R., et al. "The impact of the DWI-FLAIR-mismatch in the ECASS-4 trial – A post hoc analysis." European Stroke Journal (2020).

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