Does Vessel Occlusion Drive the Harmful Effect of Very Early Mobilization in Patients With Ischemic Stroke?: A Post Hoc Analysis of AVERT

BACKGROUND: The international trial AVERT (A Very Early Rehabilitation Trial) found that very early mobilization (VEM; commenced <24 hours after stroke) negatively affected functional outcome (modified Rankin Scale [mRS]). The drivers of this effect remain unclear. One plausible mechanism is that high-dose upright activity worsens cerebral perfusion in patients with cerebral large vessel occlusion (LVO). For this retrospective AVERT substudy, we collected brain imaging from participants from 8 AVERT sites (n=910) to explore the potential relationship between LVO, VEM, and mRS in ischemic stroke. We hypothesized that patients with evidence of LVO would be adversely affected by VEM compared with non-LVO patients. METHODS: In this post hoc analysis of a randomized controlled trial, 2 neurologists independently classified patients with ischemic stroke as having LVO via direct (vessel truncation on computed tomography/magnetic resonance imaging angiography) or indirect evidence (hyperdense artery sign or established infarction of >2/3 of an arterial territory) from brain imaging obtained ≤7 days poststroke. The associations between LVO, VEM, and 3- and 12-month mRS was tested using logistic regression, adjusted for age, treatment with thrombolysis, and baseline National Institutes of Health Stroke Scale. RESULTS: Interrater reliability for LVO signs was high (weighted κ, 0.842 [95% CI, 0.631–0.969]). Of 689 participants (37.2% female; median age, 74.5 [interquartile range, 65.0–81.2] years) included in the primary analysis, 192 (28%) showed direct or indirect evidence of LVO. Computed tomography/magnetic resonance imaging angiography were available in 179 (26%) of those 689 participants. While LVO was associated with poor mRS (>2) at 3 months (adjusted odds ratio, 2.15 [95% CI, 1.29–3.64]) and 12 months (adjusted odds ratio, 1.76 [95% CI, 1.1–2.84]; P =0.02), there was no significant interaction between VEM, LVO, and mRS ( P =0.16). CONCLUSIONS: We found no evidence that VEM was specifically harmful in patients with LVO. However, as arterial imaging was not consistently obtained before first mobilization, larger prospective studies with standardized measures of LVO are needed to fully address this question. REGISTRATION: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=1266&isReview=true ; Unique identifier: ACTRN12606000185561.