Late presenter thrombolysis for ischemic stroke between 4.5-24 hours after last known well: a retrospective cohort study

Background Two RCTs demonstrated efficacy and safety of IV alteplase for patients with acute ischemic stroke (AIS) who awaken with symptoms or with last known well (LKW) more than 4.5 hours prior to arrival. However, real world experience using CT perfusion (CTP) or DWI-MRI for patient selection in the U.S. is limited. We developed the Tufts Late Presenter Thrombolysis (LPT) protocol to offer alteplase to patients with wakeup stroke, known LKW more than 4.5 hours, or unknown LKW likely more than 4.5 hours and less than 24 hours, using CTP or DWI-MRI to aid patient selection. Methods We reviewed ED stroke codes from our Comprehensive Stroke Center between 1/1/20-12/31/22 to identify patients treated with alteplase. Data were collected on demographics, comorbidities, LKW-to-treatment time (LTT), imaging modality, imaging findings, NIHSS, vessel occlusions, endovascular therapy (EVT), symptomatic ICH, and 90 days mRS. Outcomes for comparative analyses included process times (door to needle, door to CT) and clinical outcomes (90 day mRS, symptomatic ICH). Results Forty-three of 118 patients (36%) presenting with AIS and treated with thrombolysis were treated between 4.5-24 hours after LKW. Patients treated in the 4.5 hour window and the later window had similar demographics, comorbidities, NIHSS, and EVT rates. CTP was used in the majority of LPT cases. The median penumbra was 45.04 mL (11.55-83.21), and the median core infarct was 5.92 mL (1.89-16.7). Symptomatic intracranial hemorrhage occurred in one LPT case (2.3%). Favorable mRS (0-1) was achieved by 36% of LPT patients with documented 90 day mRS. Conclusions A pragmatic protocol offering thrombolysis to late presenters may be safe and achieve favorable outcomes.