Abstract Rationale Sepsis, a life-threatening syndrome driven by a dysregulated host response to infection, remains a major cause of global mortality among critically ill adults. Beyond their lipid-lowering effects, statins, particularly atorvastatin, demonstrate pleiotropic anti-inflammatory, immunomodulatory, and endothelial-stabilizing properties, which may provide therapeutic benefit in the septic milieu. This systematic review and meta-analysis evaluated whether adjunctive atorvastatin therapy reduces mortality in adult patients with sepsis. Methods A systematic search was conducted in PubMed, Cochrane Library, and Embase databases through November 2025 to identify randomized controlled trials (RCTs) comparing atorvastatin to placebo or standard care in adult septic patients. Two independent reviewers screened studies and extracted data. A random-effects model was applied, and statistical heterogeneity was quantified using the I² statistic. Analyses were performed using Review Manager (RevMan). This meta-analysis adhered to PRISMA and Cochrane guidelines. Results Eight RCTs published between 2011 and 2025 were included, totaling 795 adult septic patients. Pooled analysis showed that atorvastatin therapy was associated with a significant reduction in mortality compared with control (OR 0.67; 95% CI 0.46-0.98; Z = 2.06; P = 0.04), corresponding to approximately 33% lower odds of death. Heterogeneity across studies was negligible (Tau² = 0.00; Chi² = 5.12, df = 7; P = 0.65; I² = 0%), indicating consistency across trial results. Although individual event rates varied, a consistent survival trend favoring atorvastatin was observed. Sensitivity analyses demonstrated similar findings, supporting robustness of results. Conclusion Atorvastatin use in adult septic patients was associated with a statistically significant reduction in mortality, supporting a potential protective role of statins in sepsis. Although encouraging, these results highlight the need for larger, rigorously designed RCTs to confirm benefits, define optimal timing and dosing strategies, and identify patient subgroups most likely to benefit from statin therapy in sepsis. This abstract is funded by: None
Pereira et al. (Fri,) studied this question.