Early mortality and hospitalization following cholangiocarcinoma diagnosis by statin exposure: A TriNetX real-world analysis.

Abstract

11195 Background: Statins are widely prescribed among patients with cardiometabolic comorbidities and are frequently continued at the time of cancer diagnosis. While statins have been hypothesized to exert antitumor and immunomodulatory effects, real-world data evaluating early clinical outcomes associated with statin exposure in patients with cholangiocarcinoma are limited. We assessed short-term mortality and hospitalization outcomes following cholangiocarcinoma diagnosis using a large federated electronic health record network. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network, comprising 68 healthcare organizations. Adult patients (≥18 years) diagnosed with intrahepatic bile duct carcinoma (ICD-10 C22.1), extrahepatic bile duct carcinoma (C24.0), or ampullary carcinoma (C24.1) between January 1, 2010, and December 11, 2024 were included. Patients were classified based on exposure to statins (rosuvastatin, simvastatin, fluvastatin, pravastatin, lovastatin, atorvastatin, or pitavastatin) within a prespecified temporal window relative to cancer diagnosis, with the index event defined accordingly. Propensity score matching (1:1) was performed to balance demographics, comorbidities, and laboratory characteristics, mitigating confounding by indication and immortal time bias. Outcomes included all-cause mortality, hospitalization, and sepsis at 30 and 90 days following the index event. Risk estimates and Kaplan–Meier survival analyses were performed. Results: After propensity score matching, baseline characteristics were well balanced between statin-exposed and non–statin-exposed cohorts. At 30 days following diagnosis, statin exposure was not associated with a significant difference in all-cause mortality. In contrast, at 90 days, statin exposure was associated with higher all-cause mortality (risk ratio 1.23; hazard ratio 1.30; log-rank P = .012) and increased hospitalization (risk ratio 1.29; hazard ratio 1.37). No significant differences in sepsis risk or hazard were observed between cohorts at either time point. Conclusions: In this real-world, propensity score–matched analysis of patients with cholangiocarcinoma, statin exposure was not associated with improved 30-day survival and was associated with higher 90-day mortality and hospitalization. Although causality cannot be inferred, these findings highlight clinically meaningful early outcome differences during the peri-diagnostic period and suggest that commonly prescribed cardiovascular medications may identify patients with increased baseline vulnerability at the time of cancer diagnosis. Future work integrating medication exposure with comorbidity burden, treatment patterns, and early care trajectories may help refine risk stratification during initial cholangiocarcinoma management.