Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

“…A systematic review and individual participant data meta-analysis of RCTs of IVT with alteplase for patients with stroke of unknown time of onset guided by advanced imaging was recently conducted by the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators. 46 A total of 843 patients enrolled in studies based on DWI-FLAIR mismatch (WAKE-UP 39 and THAWS 44 ) or core/perfusion mismatch (EXTEND 29 and ECASS-4 30 ) were included. Perfusion data was automatically reprocessed using the RAPID software, and the authors used the definition of penumbral mismatch from the EXTEND trial for their analysis (infarct core volume ≤70 ml, absolute perfusion lesion volume of >10 ml and mismatch ratio between perfusion and core >1.2).…”

“…30 Based on the perfusion mismatch criteria of each original study, the association would not have been significant (OR 1.56; 0.81–3.02). 34 Of note, in the EOS individual participant data meta-analysis, only 54% ( n = 221) of patients with available assessment for perfusion imaging had a penumbral mismatch according to the EXTEND criteria 46 . However, because this analysis showed a clear benefit of IVT (adjusted OR for excellent outcome 2.14, 95% CI: 1.11–4.12), we provide a strong recommendation in favour of IVT in this situation.…”

“…Quality of evidence: High Strength of recommendation: Strong "" For patients with acute ischaemic stroke on awakening from sleep, who have CT or MRI core/perfusion mismatch * within 9 h from the midpoint of sleep, and for whom mechanical thrombectomy is either not indicated or not planned, we recommend intravenous thrombolysis with alteplase. Quality of evidence: Moderate Strength of recommendation: Strong "" * In the EOS individual participant data meta-analysis, 46…”

Acute ischemic stroke care in Germany – further progress from 2016 to 2019

“…The “WAKE-UP” stroke trial published in May 2018 [ 18 ] might have had an impact on the increasing IVT rate observed in 2019. We do expect a further increase of the overall IVT use in the wake of the Extend trial [ 19 ], ECASS4 [ 20 ] and the subsequent individual patient data meta-analysis [ 29 ], given that the incidence of wake-up and unknown time window strokes is estimated to be between 15 and 25% [ 30 ].…”

Expanding the therapeutic window in acute ischemic stroke by advanced imaging

“…Recently, the meta-analysis for wake-up trials was published [47] , including WAKE-UP (DWI-FLAIR mismatch), THAWS (DWI-FLAIR mismatch), ECASS4 (PWI-core mismatch), and EXTEND (PWI-core mismatch) [48] . The two different radiological approaches to expand the time window are interesting, while the PWI-core mismatch selection group also published a meta-analysis including EXTEND, ECASS4-EXTEND, and EPITHET [49] .…”