Abstract
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited disease-modifying therapies and a poor overall prognosis. Statins, are commonly used for dyslipidemia, and have been proposed to exert cholesterol-independent actions including anti-inflammatory and potential neuroprotective effects. Prior studies, However, existing studies offer conflicting results regarding their impact on ALS survival. This systematic review and meta-analysis aimed to evaluate the association between statin use and survival outcomes in patients with ALS. METHODS: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science from inception to September 2025. Studies were included if they reported survival outcomes for statin users vs. non-users among patients with ALS. Data on hazard ratios (HRs) were extracted and pooled using fixed- or random-effects models, depending on heterogeneity. Meta-regression and sensitivity analyses were performed to explore the influence of covariates such as age and gender. RESULTS: Six studies with 3,739 participants (889 statin users) met the inclusion criteria. The pooled analysis showed no statistical significant association between statin use and ALS survival [Log(HR) = -0.04; 95% CI: -0.18 to 0.10], with moderate heterogeneity (I (2) = 24.85%). CONCLUSION: The pooled estimate in this meta-analysis did not show a statistically significant association between statin use and ALS survival; however, the evidence is limited by heterogeneity in statin exposure definitions and likely residual confounding in predominantly observational data. Further high-quality studies with large sample sizes are needed to determine whether specific subgroups may benefit/harm from statin therapy. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251160344; PROSPERO: CRD420251160344.