Value of 24- to 48-Hour Infarct Volume as a Surrogate for Clinical Outcome in Late-Window Thrombectomy May Be Limited: A Post Hoc Analysis of the AURORA Collaboration

BACKGROUND: – The utility of 24- to 48-hour follow-up infarct volume (FIV) as a surrogate outcome in late time-window acute ischemic stroke is unclear. We aimed to determine associations of 24- to 48-hour FIV and clinical outcome in patients presenting >6 hours from last known well with and without endovascular treatment (EVT). METHODS: – Post hoc analysis of the AURORA (Thrombectomy for Anterior Circulation Stroke Beyond 6 h From Time Last Known Well) patient-level meta-analysis of 6 randomized trials of late-window EVT. Patients were randomized to EVT or the control arm (best medical care). FIV was assessed on follow-up computed tomography or magnetic resonance imaging at 24 to 48 hours. Multivariable binary logistic regression with adjustment for key covariates was performed to estimate probabilities of achieving functional independence (modified Rankin Scale [mRS] score, 0–2 at 90 days) based on FIV. Mediation analysis was performed to determine the proportion of the EVT effect that is explained by FIV reduction. RESULTS: – Four hundred forty-nine patients of 505 patients (88.9%) had available FIV and 90-day mRS and were included. Patients with worse outcomes at 90 days had larger FIV (median FIV in 90-day mRS score, 1:13.7 mL [interquartile range, 6.1–31.3] versus mRS score, 6:59.6 [18.8–145.0]; P<0.01). In the EVT arm, the estimated probability of achieving an mRS score of 0 to 2 declined with increasing FIV, from 65% at 0 mL FIV to 4% at 200 mL. In the control arm, this association was weaker, and the mRS score of 0 to 2 probabilities were overall lower. Only 5.9% of EVT’s effect on clinical outcome was explained by FIV reduction. CONCLUSIONS: – FIV mediated only a small proportion of the EVT effect on clinical outcome, and the association of FIV and outcomes was much weaker; overall outcomes were worse in the control arm compared with the EVT arm. For FIV up to 100 mL, EVT results in substantially better clinical outcomes than best medical management given the same FIV. The utility of FIV as a surrogate outcome in late time-window stroke may be limited.