Effect of Acetylsalicylic Acid on Mortality in Sepsis: A Systematic Review and Meta-Analysis

Background The association between aspirin and mortality in patients with sepsis remains unclear. This study aimed to systematically evaluate the effects of aspirin on mortality and major bleeding in adults with sepsis. Methods This review was registered in Open Science Framework (DOI: 10.17605/OSF.IO/E5K87). We searched MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov through May 9, 2025. We included one randomized controlled trial (RCT) and four non-randomized studies of interventions (NRSIs). Risk of bias was assessed using RoB 2 for RCTs and ROBINS-I for NRSIs. Random-effects meta-analysis was performed. Results Five studies involving 25 138 patients were included. Aspirin showed a possible reduction in mortality (RR 0.77, 95% CI 0.66-0.89; I 2 = 61.9%), but the certainty of evidence was very low. No clear effect was observed on major bleeding (OR 1.20, 95% CI 0.46-3.11; I 2 = 77.3%), also with very low certainty. Data for secondary outcomes (SOFA score, ICU length of stay) was sparse and very uncertain. Subgroup analyses showed no evidence of effect modification by aspirin timing or treatment setting, and sensitivity analyses limited to Sepsis-3 studies and exclusion of Wang et al produced similar results. Evidence was limited by the predominance of NRSIs, heterogeneity in sepsis definitions, and variability in dosing and timing of aspirin. Conclusions The evidence is very uncertain regarding the effect of aspirin on mortality or bleeding in sepsis. Routine aspirin use for patients with sepsis cannot be recommended. For patients already receiving aspirin before hospitalization, continuation should be guided by clinical judgment. Further high-quality RCTs are warranted.