The association between cardiovascular medication use and survival in patients with advanced pancreatic adenocarcinoma

Background: Advanced pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and limited therapeutic options. Drug repurposing offers a cost-effective strategy to identify agents with potential synergistic benefits and known safety profiles. Preclinical and retrospective studies suggest that renin–angiotensin–aldosterone system inhibitors (RAASi) and statins may enhance chemotherapy efficacy by modulating the tumor microenvironment and oncogenic signaling. Objectives: To explore associations between cumulative RAASi and/or statin use and overall survival (OS) in elderly patients with advanced PDAC receiving first-line chemotherapy, as hypothesis-generating adjunct exposures. Methods: We analyzed a population-based registry using linked administrative databases from Ontario, Canada, identifying patients aged ⩾67 years with advanced PDAC who received first-line gemcitabine/nab-paclitaxel or mFOLFIRINOX between 2015 and 2024. The primary outcome was OS. Associations between cumulative RAASi or statin exposure and OS were assessed using multivariable Cox proportional hazards models, treating cumulative drug exposure as a time-varying covariate to mitigate immortal time bias. Results: Among 3226 eligible patients, the median age was 73 years, and 44% were female. Forty-one percent received both RAASi and statins, 17% statins alone, 14% RAASi alone, and 28% neither. Median OS was 7.9 months across groups. On multivariable analysis, neither cumulative RAASi (hazard ratio (HR) 1.00, 95% CI 0.98–1.02) nor statin exposure (HR 1.00, 95% CI 0.98–1.02) was associated with improved survival. Conclusion: In this large cohort of advanced PDAC patients undergoing first-line chemotherapy, real-world, non-targeted RAASi and statin use was not associated with improved OS. These findings highlight the need for rigorously designed prospective studies to validate repurposed drug candidates before clinical adoption. Design: Retrospective population-based cohort study.