(766) Biomarkers and Clinical Outcomes in Traumatic Brain Injury Patients Receiving High-Dose Atorvastatin

Introduction: Biomarkers released after TBI have been linked to injury severity and are potential TBI drug treatment monitoring targets. Previous preclinical trials evaluating atorvastatin’s effects on neurological outcomes suggest that statins may reduce post-TBI inflammation and neuronal loss in contused tissue and hippocampus, and enhance neurogenesis and angiogenesis. This study aims to evaluate biomarker trends and outcomes in patients receiving preinjury or in-hospital high-dose atorvastatin (HD-ATOR).

Methods: This is a retrospective cohort study utilizing the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) database, conducted at 18 level-1 trauma centers in the US from 2014-2018. Patients were assessed for clinical outcomes with follow-up for 12 months post-TBI. TBI patients ≥ 17 years old were included. Patients receiving preinjury or in-hospital HD-ATOR (40mg, 80mg) were compared to propensity-matched controls. Clinical outcome was evaluated using various assessment tools at 2 weeks, 3 and 6 months post-TBI. Plasma biomarker mean peak concentrations (Cp) post-injury were analyzed for GFAP, UCHL-1, NSE, S100, CRP, NFL, IL-10, IL-6, TNF-𝛼, and tau.

Results: Mean GFAP and Tau Cp at day 3 were 59.5% and 75.5% lower, respectively, in HD-ATOR (n=54) as compared to controls (n=312). Mean NFL Cp at 2 weeks was 64.2% lower. On day 1, mean CRP Cp was lower in HD-ATOR by 36% and displayed a downward trend on days 1-5 with a Cp 96.5% lower than controls. Although these downward trends may be clinically meaningful, they were not statistically significant. The HD-ATOR group showed a beneficial effect on all clinical assessments at 2 weeks and 6 months. At 2 weeks, the mean Rivermead score was 4.2 points (p=0.036) lower as compared to control.

Conclusions: Preinjury or in-hospital treatment with HD-ATOR showed promising trends in select TBI biomarker concentrations and improved clinical assessment scores. Due to a small sample size and multiple comparisons between groups, most results were not statistically significant. Prospective atorvastatin neuroprotective studies are needed to confirm these favorable clinical outcomes and biomarkers as potential drug monitoring targets.