Abstract / Summary
ABSTRACT Background Pharmacologic therapies to prevent decompensation in cirrhosis remain limited. Aim To evaluate the association between aspirin use and cirrhosis‐related outcomes and mortality. Methods This retrospective cohort study utilized deidentified electronic health records from a global federated network (January 2013–July 2025). Adults with cirrhosis without decompensation in the preceding 12 months and without prior HCC were included. Following 1:1 propensity score matching, outcomes were assessed at 12, 24, and 36 months. The primary outcome was a composite of cirrhosis‐related decompensation (ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, encephalopathy). Secondary outcomes included hepatocellular carcinoma (HCC), mortality, and gastrointestinal bleeding. Results Among 458 165 patients, matching yielded 25 782 patients (12 891 per group; mean age 63.3 years). Aspirin was associated with a lower risk of the composite outcome at 12 (HR, 0.75; 95% CI, 0.67–0.83), 24 (HR, 0.76; 95% CI, 0.70–0.84), and 36 months (HR, 0.77; 95% CI, 0.68–0.84), driven by reduced variceal bleeding, spontaneous bacterial peritonitis, and ascites. Absolute risks were 17.8% vs. 22.7% at 12 months, 20.4% vs. 24.7% at 24 months, and 22.0% vs. 25.7% at 36 months. At 12 months, the NNT was 21 for the composite outcome and 20 for mortality. Despite an increased risk of nonvariceal bleeding (NNH 143 at 12 months), serving as a positive control outcome, aspirin demonstrated a net clinical benefit, with more pronounced benefits in high cardiovascular risk patients ( p interaction < 0.05). Conclusions Aspirin use is associated with reduced cirrhosis complications, HCC, and mortality, suggesting a potential role in the management of compensated cirrhosis.