Impact of Aspirin on Clinical Outcomes in Sepsis Patients with Atrial Fibrillation: An Analysis of the MIMIC-IV and eICU-CRD Databases

Background :Sepsis features dysregulated inflammation, endothelial dysfunction, platelet activation, and immunothrombosis; concomitant Atrial Fibrillation(AF) may further intensify prothrombotic and proinflammatory signaling, thereby increasing thrombotic risk and mortality. Aspirin may provide benefit through platelet inhibition and modulation of inflammatory and immune pathways. However, evidence for aspirin use in sepsis patients with comorbid AF is limited, and its clinical value and risk-benefit profile remain unclear. Objective : To evaluate the association between aspirin treatment and prognosis in sepsis patients with AF, including in-hospital gastrointestinal bleeding (GIB). Methods :In MIMIC-IV, propensity score matching balanced baseline characteristics. Kaplan–Meier analyses compared 28-day and 1-year all-cause mortality between aspirin and non-aspirin groups, and multivariable Cox proportional hazards models assessed independent associations. Multivariable logistic regression evaluated in-hospital GIB. External validation was performed in eICU-CRD. Time-dependent Cox regression assessed temporal associations, with subgroup and stratified analyses by anticoagulant use, AF patterns, comorbidities, aspirin dose, duration, and initiation timing. Results :Aspirin use was associated with lower 28-day mortality (16.06% vs. 23.70%) and 1-year mortality (21.03% vs. 29.22%) (both P<0.001), with consistent Kaplan–Meier differences (P<0.001). Aspirin was independently associated with improved 28-day survival and was not independently associated with in-hospital GIB. Findings were validated in eICU-CRD. Time-dependent Cox models confirmed reduced mortality. Effects were significant in subgroups with AF detected during hospitalization (both P<0.05). Initiation after sepsis diagnosis or ICU admission were associated with reduced mortality (both P<0.001). Conclusion :Aspirin treatment is significantly associated with reduced all-cause mortality in sepsis patients with AF.