Statin Therapy in Ischemic Stroke Models: A Meta-Analysis

Abstract

Statins, drugs known for lipid lowering capabilities and reduction of cardiovascular disease, have demonstrated neuroprotective effects following ischemic stroke in retrospective clinical and animal studies. However, dosing (methods, time, type of statin, and quantity) varies across studies, limiting the clinical applicability of these findings. Furthermore, a comprehensive review of statins in edema and blood-brain barrier (BBB) breakdown is needed to provide insight on diverse, less explored neuroprotective effects. In the present study, we conduct a meta-analysis of publications evaluating statin administration in animal models of ischemic stroke. We review statins’ most effective dosing regimen in four outcomes—infarct, edema, BBB breakdown, and functional outcome—to characterize several parameters of benefit associated with statin administration. A search term was constructed to identify experimental murine studies exploring statin use after transient middle cerebral artery occlusion (tMCAO) in PubMed, Web of Science, and Embase. Extracted data included statin type, dose, time and method of administration, and the four predetermined outcomes (functional outcome, edema, BBB breakdown, and infarction). A meta-analysis and stratified meta-regression were conducted using the standardized mean difference (SMD) method for continuous measurements. Included publications were assessed for bias using SYRCLE’s RoB tool for animal studies. A total of 24 studies were included. Statin administration significantly reduced infarct volume ( p < 0.0001), edema volume ( p < 0.002), and neurological deficit ( p < 0.0001). Simvastatin and pravastatin were most effective in reducing infarct volume when compared with atorvastatin ( p = 0.0475, p = 0.0004) and rosuvastatin ( p = 0.0036, p < 0.0001). Pravastatin outperformed all others in functional outcome. Subcutaneous (SC) injection was most effective in all outcomes. Statin therapy reduced BBB breakdown according to our systematic review. Mean study quality was 4.6/10. While statin therapy evidently improves neurological outcome following ischemic stroke, this analysis adds to our understanding of dosing and statins’ effects on edema and BBB breakdown. These findings will aid the design of future studies investigating statin use and have larger implications for the clinical care of ischemic stroke patients.