Salvageable Time Window: Tissue Clock After Acute Ischemic Stroke Onset

Salvageable ischemic tissue has become the treatment target of endovascular therapy (EVT). This study proposed a new concept of salvageable time window that measures the dynamic process of salvageable tissue. We hypothesized that patients who received EVT beyond the salvageable time window would have limited benefits. This was a retrospective multicenter study based on the INSPIRE (International Stroke Perfusion Imaging Registry), enrolling patients with acute ischemic stroke due to large vessel occlusion within 6 hours of stroke onset (August 2011-April 2022, 22 sites). Patients were divided into 3 groups: EVT delivered within the salvageable time window, EVT delivered outside the salvageable time window, and a historical no EVT control. Salvageable time window was calculated by salvageable tissue volume divided by core growth rate, which estimates the time for infarction expanding to the whole ischemic region. Patients were considered outside the window if EVT was initiated after their estimated salvageable window. The primary outcome was a good functional outcome defined by 3-month modified Rankin Scale score of 0 to 2. Propensity score matching was applied to reduce selection bias among groups. Overall, 1291 patients (mean age 70.3 years, 43.6% female) were included in the study, with 456 in the no EVT group, 727 in the EVT within salvageable time window group, and 108 in the EVT outside salvageable time window group. After propensity score matching (n=62 per group), patients received EVT within the salvageable time window had higher odds of good functional outcome compared with those with no EVT (48% versus 29%, odds ratio, 2.29 [95% CI, 1.09-4.81]; P=0.028), without increased risk of bleeding (type 2 parenchymal hematoma of 2% versus 3%, odds ratio, 0.49 [95% CI, 0.04-5.57]; P=0.566). In contrast, patients received EVT outside the salvageable time window did not show improved 3-month functional outcomes (32% versus 29%, odds ratio, 1.16 [95% CI, 0.54-2.50]; P=0.697) and demonstrated an increased bleeding risk (type 2 parenchymal hematoma of 17% versus 3%, odds ratio, 5.83 [95% CI, 1.22, 27.9]; P=0.027). This study indicates the importance of estimating the salvageable time window within 6 hours of stroke onset, as initiating endovascular treatment beyond salvageable time window may not benefit.