Duration of Ischemia Impacts Postreperfusion Clinical Outcomes Independent of Follow-Up Infarct Volume

Time to reperfusion is believed to influence clinical outcomes following thrombectomy mainly through reduction of infarct growth. In this study, we aim to understand whether clinical outcomes can be influenced by ischemia duration (penumbral time) independent of postintervention infarct volume by comparing outcomes following thrombectomy in patients with similar (and small) follow-up infarct volumes.

We performed a retrospective analysis of a prospectively maintained large-vessel occlusion stroke thrombectomy database across 3 US centers. Demographic, clinical, radiological, and outcomes data of patients with anterior circulation large-vessel occlusion (internal carotid or middle cerebral artery M1) stroke who had a witnessed-onset stroke, had substantial penumbral volumes, achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b-3), and had a follow-up infarct volume of <20 mL were analyzed.

A total of 233 patients (center A, 25; center B, 33; center C, 175) were included. Mean age was 71±16 years, and median National Institutes of Health Stroke Scale was 15 (10-20). Median penumbral time was 4.7 (2.9-10) hours, and median follow-up infarct volume was 4.7 (0.2-9.4) mL. Despite comparable baseline characteristics and 24-hour infarct volumes, patients reperfused in the 0- to 6-hour time window had significantly higher rates of modified Rankin scale 0 to 2 (61% versus 40%; P=0.002) and numerically lower rates of mortality (11% versus 17%; P=0.16) at 90 days when compared with patients reperfused in the 6- to 24-hour time window. Duration of ischemia is an independent predictor of modified Rankin scale 0 to 2 (odds ratio, 0.91 [0.80-0.99]; P=0.012). In multivariable analysis accounting for age and baseline National Institutes of Health Stroke Scale score, the association between penumbral time and modified Rankin scale 0 to 2 remained significant (absolute risk difference, -1.2% [(95% CI, -1.9 to -0.4)]/h delay).

Longer penumbral duration is associated with a lower likelihood of functional independence among large-vessel occlusion strokes with small and comparable 24-hour follow-up infarct volume. Our findings indicate that delays in time to reperfusion affect clinical outcomes through mechanisms mediated by factors not solely limited to infarct reduction.