Drug Effectiveness

3A-03 - The association between the use of RAAS inhibitors and prevention of new-onset pancreatic cancer: A target trial emulation

Monday, August 25, 2025

8:45 AM - 9:00 AM ET

Presenting Author(s)

FD

Fanxing Du

Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, United States

Co-Author(s)

TS

Thomas D. Schmittgen

Department of Pharmaceutics, College of Pharmacy, University of Florida, United States
YG

Yi Guo

University of Florida, United States
FK

Farzin Khosrow-Khavar

Department of Biostatistics and Epidemiology, School of Public Health, Rutgers, The State University of New Jersey, United States
QL

Qing Liu

Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, United States
CP

Corey M. Perkins

Department of Pharmaceutics, College of Pharmacy, University of Florida, United States
JJ

Jinmai Jiang

Department of Pharmaceutics, College of Pharmacy, University of Florida, United States
DD

David Deremer

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, United States
CM

Caitrin W. McDonough

Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, United States
YL

Yi Lian

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, United States
TG

Thomas J. George

University of Florida, United States
Tianze Jiao

Assistant Professor
Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Florida, United States

Background: Pancreatic cancer is the 3rd leading cause of U.S. cancer deaths due to late diagnosis and marginally effective treatments. Pancreatic ductal adenocarcinoma (PDAC) represents 95% of pancreatic cancers, and it originates following a combination of genetic mutations and cellular changes like acinar ductal metaplasia (ADM). Pre-clinical studies by our team showed that the renin-angiotensin-aldosterone system (RAAS) is the most activated and inhibited pathway during ADM and ADM reversal, respectively. Thus, we hypothesize RAAS inhibitors may delay the onset of PDAC.

Objectives: To investigate whether RAAS inhibitors use is associated with a lower risk of pancreatic cancer compared to calcium channel blockers (CCBs).

Methods: We emulated a new user, active comparator trial using a 15% sample of Medicare beneficiaries in the United States from 01/01/2011 to 12/31/2020. Patients entered the base cohort when newly prescribed with an antihypertensive medication. Then, they were randomly assigned to initiate RAAS inhibitors or CCBs as the exposure and control group, respectively. The date of initiation was defined as index date. We included patients aged > 65 years, and had 1-year continuous Medicare enrollment before the index date. Patients diagnosed with any malignant cancer within 1 year before the index date were excluded. Our outcomes included pancreatic cancer and all-cause mortality. A 1-year latent period was applied to account for potential delayed medication effects on carcinogenesis or tumor promotion. We used propensity score matching with 2:1 ratio including 42 baseline covariates (i.e. demographics, comorbidities, and medications). Patients were followed until an outcome, death, Medicare disenrollment, or study end, whichever came first. Cox proportional hazards models with inverse probability censoring weights (accounted for informative censoring) were used to estimate hazards ratios (HR) with 95% confidence intervals (CI).

Results: After matching, we included 214,262, and 107,131 patients in RAAS and CCB groups, respectively, with the mean age of 76.5 vs. 77.0, 60.9% vs. 61.8% of female and the mean follow-up time of 2.2 vs. 1.7 years. The incidence rate of pancreatic cancer was significantly lower in the RAAS group than CCB group (0.05 vs 0.08/100 person-years, HR: 0.54, 95% CI: 0.49 – 0.59). The all-cause mortality of patients in RAAS group was significantly lower than patients used CCBs (4.44 vs 5.89/100 person-years, HR: 0.78, 95% CI: 0.77 – 0.79).

Conclusions: RAAS inhibitors are associated with a lower risk of pancreatic cancer and all-cause mortality versus CCB. This potential RAAS inhibitor benefit requires further study, accounting for confounders like genomics and biomarkers.