Thrombolysis for Wake-Up Stroke Versus Non–Wake-Up Unwitnessed Stroke: EOS Individual Patient Data Meta-Analysis
Authors: Kamogawa Naruhiko , Miwa Kaori , Toyoda Kazunori , Jensen Märit , Inoue Manabu , Yoshimura Sohei , Fukuda-Doi Mayumi , Kitazono Takanari , Boutitie Florent , Ma Henry , Ringleb Peter , Wu Ona , Schwamm Lee H. , Warach Steven , Hacke Werner , Davis Stephen M. , Donnan Geoffrey A. , Gerloff Christian , Thomalla Götz , Koga Masatoshi , Cheng Bastian , Bendszus Martin , Bladin Christopher , Churilov Leonid , Campbell Brunce , Parsons Mark , Yassi Nawaf , Ebinger Martin , Endres Matthias , Fiebach Jochen B. , Kleinig Timothy , Latour Lawrence , Lemmens Robin , Levi Christopher , Leys Didier , Molina Carlos , Muir Keith , Nighoghossian Norbert , Pedraza Salvador , Schellinger Peter D. , Schwab Stefan , Simonsen Claus Z. , Song Shlee S. , Thijs Vincent , Toni Danilo , Hsu Chung Y. , Wahlgren Nils 
Published: September 2024

BACKGROUND:
Stroke with unknown time of onset can be categorized into 2 groups; wake-up stroke (WUS) and unwitnessed stroke with an onset time unavailable for reasons other than wake-up (non–wake-up unwitnessed stroke, non-WUS). We aimed to assess potential differences in the efficacy and safety of intravenous thrombolysis (IVT) between these subgroups.

METHODS:
Patients with an unknown-onset stroke were evaluated using individual patient-level data of 2 randomized controlled trials (WAKE-UP [Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke], THAWS [Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg]) comparing IVT with placebo or standard treatment from the EOS (Evaluation of Unknown-Onset Stroke Thrombolysis trial) data set. A favorable outcome was prespecified as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage at 22 to 36 hours and 90-day mortality. The IVT effect was compared between the treatment groups in the WUS and non-WUS with multivariable logistic regression analysis.

RESULTS:

Six hundred thirty-four patients from 2 trials were analyzed; 542 had WUS (191 women, 272 receiving alteplase), and 92 had non-WUS (42 women, 43 receiving alteplase). Overall, no significant interaction was noted between the mode of onset and treatment effect (
P
value for interaction=0.796). In patients with WUS, the frequencies of favorable outcomes were 54.8% and 45.5% in the IVT and control groups, respectively (adjusted odds ratio, 1.47 [95% CI, 1.01–2.16]). Death occurred in 4.0% and 1.9%, respectively (
P
=0.162), and symptomatic intracranial hemorrhage in 1.8% and 0.3%, respectively (
P
=0.194). In patients with non-WUS, no significant difference was observed in favorable outcomes relative to the control (37.2% versus 29.2%; adjusted odds ratio, 1.76 [0.58–5.37]). One death and one symptomatic intracranial hemorrhage were reported in the IVT group, but none in the control.

CONCLUSIONS:
There was no difference in the effect of IVT between patients with WUS and non-WUS. IVT showed a significant benefit in patients with WUS, while there was insufficient statistical power to detect a substantial benefit in the non-WUS subgroup.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: CRD42020166903.