Abstract

Data on the association between aspirin and statin use and Pancreatic Ductal AdenoCarcinoma (PDAC) risk are conflicting. These drugs are often co-prescribed, but no studies evaluated the potential combined or confounding effect of the two at the same time. We aimed to investigate the association between aspirin and statin exclusive and combined use and PDAC occurrence. Data on environmental factors, family and medical history were screened in a case-control study. PDAC cases were matched to controls for age and gender. Power calculation performed ahead. Odds ratios (OR) and 95% confidence intervals(CI) were obtained from multivariable logistic regression analysis. In 408 PDAC patients and 816 matched controls, overall statin (OR 0.61; 95%CI,0.43–0.88), but not aspirin use was associated to reduced PDAC risk. Compared to non-users, exclusive statin (OR 0.51; 95%CI,0.32–0.80) and exclusive aspirin users (OR 0.64; 95%CI,0.40–1.01) had reduced PDAC risk. Concomitant statin and aspirin use did not further reduce the risk compared with statin use alone and no interaction was evident. Statin protective association was dose-dependent, and consistent in most subgroups, being stronger in smokers, elderly, obese and non-diabetic patients. The present study suggests that statin use is associated to reduced PDAC risk, supporting a chemopreventive action of statins on PDAC.

Highlights

  • Aspirin is a nonsteroidal anti-inflammatory drug (NSAID), irreversible inhibitor of the cyclooxygenase 1/2, widely prescribed for its anti-inflammatory, antipyretic, analgesic and anti-platelet activities

  • This led to a participation rate of 99% for cases and 91% for controls; the analysis was conducted on a final population of 408 cases and 816 matched controls

  • Pancreatic Ductal AdenoCarcinoma (PDAC) risk is inversely associated with the overall statin use, with a dosage-dependent effect

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Summary

Introduction

Aspirin is a nonsteroidal anti-inflammatory drug (NSAID), irreversible inhibitor of the cyclooxygenase 1/2, widely prescribed for its anti-inflammatory, antipyretic, analgesic and anti-platelet activities. Its role in clinical studies on PDAC is less clear, and the most recent meta-analysis on cohort and case-control studies, showed an overall protective effect of aspirin with an odds ratio (OR) of 0.77, with high heterogeneity[13]. Is related with an immunomodulatory and anti-inflammatory activity and with angiogenesis inhibition[18,19] Their clinical role as chemopreventive agents is still controversial, a few meta-analyses showed a risk reduction associated with their use, mostly for gastrointestinal tract tumours[20,21,22]. The latest meta-analysis on the association between statin use and PDAC risk showed no pooled effect[23]. Since other large case-control studies were published[24,25], recording a reduced PDAC risk associated with statin use. The authors reported a stronger risk reduction for statin exclusive use than for that of aspirin, while the combination of the two drugs did not further increase the effect of statins, unless for prolonged uses[26]

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