Abstract WMP92: Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes After Acute Ischemic Stroke: An Analysis of the DAWN Trial

Abstract

Introduction: In the early window, time to treatment with endovascular thrombectomy (EVT) is inversely associated with favorable clinical outcomes but this remains unclear in the extended window. We aimed to assess the impact of time to EVT on clinical outcomes in the DAWN trial. Methods: The association between every 1-hour treatment delay with 90-day functional independence (modified Rankin Scale [mRS] 0-2), symptomatic intracranial hemorrhage (SICH), and 90-day mortality was explored in the overall population and in three modes of onset subgroups (wake-up vs witnessed vs unwitnessed) considering both time from last seen well (TLSW) and time from symptoms first observed (TSFO). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6-12-hour and 12-24-hour time window, respectively. Considering all three modes of onset together, there was no statistically significant association between TLSW to randomization with either functional independence or mortality at 90 days in either the EVT (mRS0-2 OR 1-hour-delay:1.07;95%CI[0.93-1.24]; mRS6 OR:0.84;95%CI[0.65-1.03]) or medical management (mRS0-2 OR1-hour-delay:0.98;95%CI[0.80-1.14]; mRS6 OR 1-hour-delay:0.94;95%CI[0.79-1.09]) groups. Moreover, there was no significant interaction between treatment effect and time (p=0.439 and p=0.421 for mRS 0-2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between TLSW to successful reperfusion (mTICI≥2b) and 90-day functional independence showed a significant interaction with mode of presentation (p=0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p=0.018) negative slope in wake-up patients. There was no association between treatment times and SICH. Comparable analysis using TSFO yielded similar results. Conclusion: In extended window patients, the association between time to treatment and clinical outcomes seems to be primarily driven by successfully perfused patients with wake-up rather than witnessed or unwitnessed strokes suggesting that wake-up strokes do not behave as “slow-progressors”.