Impact of Beta Blockers, Statins, and Cholinergic Agents on Clinical Outcomes in Pancreatic Cancer: A Retrospective VA Cohort Study

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BACKGROUND: Neural regulation contributes to pancreatic ductal adenocarcinoma (PDAC) development but effects of neural-targeting medications on presentation or outcomes remain unclear. METHODS: We conducted a retrospective study using the Veterans Affairs (VA) Corporate Data Warehouse (CDW) to identify patients with pancreatic cancer (2000-2020). Exposure to beta blocker, cholinergics or statins was defined by active prescriptions within 6 months before or 1 month after diagnosis. Outcomes included histologic subtype, stage, and overall survival (OS). Propensity score matching was performed for each medication class, with survival assessed using Kaplan-Meier and Cox regression models. RESULTS: Among 7,578 Veterans with pancreatic cancer, 76% had adenocarcinoma and 60% presented with stage IV disease. Beta blocker use was associated with lower odds of advanced stage (OR 0.55, 95% CI 0.5-0.63, p<0.0001) and improved OS (HR 0.89, 95%CI 0.84-0.95, p<0.0001). Cholinergic agonist use was associated with reduced likelihood of adenocarcinoma histology (OR 0.64, 95% CI 0.41-1.01, p=0.051) and advanced stage (OR 0.53, 95%CI 0.34-0.85, p=<0.0001), but not OS. Statin use was associated with adenocarcinoma histology (OR 1.24, 95%CI 1.09-1.43, p=0.002) and lower odds of advanced stage (OR 0.77, 95%CI 0.68-0.88, p=<0.0001). CONCLUSIONS: Beta blockers were associated with earlier stage and improved survival. Cholinergic agonists and statins were associated with earlier stage. Cholinergic agonists were linked to lower likelihood of adenocarcinoma histology, while statins to higher likelihood. These findings suggest neural and metabolic pathways may shape early PDAC biology. IMPACT: Autonomic and metabolic pathways may influence PDAC biology. Beta blockers merit mechanistic and clinical evaluation as adjunctive therapies.

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