Abstract TMP2: Intravenous Thrombolysis For Ischemic Stroke With Unknown Time Of Onset: Differences Between Wake-up Stroke And Non-wake-up Subtypes: EOS

Background: The unknown onset stroke can be categorized into two groups; wake-up stroke (WUS) and non-wake-up unwitnessed stroke with a time of onset unavailable due to aphasia, impaired consciousness, or cognitive impairment (non-wake-up unknown onset stroke, non-WUS). We aimed to assess the differences in efficacy and safety of intravenous thrombolysis (IVT) for these subgroups. Methods: Patients with an unknown onset stroke from the Evaluation of unknown Onset Stroke thrombolysis trials (EOS) collaboration were evaluated using an individual patient-level database of randomized controlled trials comparing IVT with placebo/standard treatment. A favorable outcome was defined as a modified Rankin Scale score 0-1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) at 22-36 hours and 90-day mortality. The effect of IVT was compared between the treatment groups in the WUS and non-WUS with mixed-effect logistic-regression analysis. Results: A total of 634 patients (233 women [36.8%], median age 70 years [IQR 61-76]) were analyzed. In patients with non-WUS (n=92 [14%]), advanced age, atrial fibrillation, vessel occlusion on MRA and high NIHSS score were more prevalent (P<0.01 for each) than those with WUS (n=542 [86%]). Overall, no significant interaction was noted between the mode of onset and treatment effect (Pinteraction=0.782). In patients with WUS, a favorable outcome was more common in the IVT group than the control (149 [54.8%] vs. 117 [45.5%], adjusted OR: 1.45, 95% CI 1.01-2.11), death occurred in 11 [4.0%] and 5 [1.9%] (p=0.099), and sICH occurred in 5 [1.8%] and 1 [0.3%] (p=0.142). In patients with non-WUS, no significant difference was observed for a favorable outcome (16 [37.2%] vs. 14 [29.2%], aOR 1.73 [0.60-4.98]). One death and one sICH were reported in the IVT group, but none in the controls. Conclusions: The benefit of IVT was significant in patients with WUS. Excellent outcome was also numerically more prevalent in non-WUS but this did not reach significance, probably due to the lack of statistical power.