Anticoagulant drugs with or without proton pump inhibitor and colorectal cancer risk: a population-based, case–control study

Background: Low-dose aspirin and clopidogrel have demonstrated potential chemoprevention for colorectal cancer (CRC). Proton-pump inhibitors (PPI) are commonly prescribed with anticoagulation drugs, but the relationship between PPI and CRC is unclear. Moreover, evidence of CRC risk under direct oral anticoagulant (DOAC) is limited. This study aimed to investigate the effects of anticoagulation drugs combined with or without PPI on the risks of CRC in Taiwan. Methods: A retrospective case–control study of 1,024,227 cases based on the Chang Gung Research Database from 2010 to 2017 was performed. Clinical characteristics, indications, duration of anticoagulation and PPI use, and CRC occurrence data were collected. Logistic regression was employed to adjust for known confounders of CRC risk. Results: Monotherapy of clopidogrel decreased the risk of CRC (AOR 0.70; 95% CI 0.60–0.83), while no protective effect was observed in aspirin alone or aspirin plus clopidogrel. DOAC did not affect CRC significantly. The risk of CRC increased in patients with PPI (AOR 1.38; 95% CI 1.28–1.49) and PPI plus DOAC (OR 3.91; 95% CI 1.49–10.27), while PPI plus aspirin decreased the risk of CRC (OR 0.48; 95% CI 0.32–0.73). PPI plus clopidogrel showed no significant effect on the CRC. Conclusion: This study suggests clopidogrel alone and PPI plus aspirin offer a preventative benefit against CRC in the Taiwanese population studied. The same effect was not observed in DOAC. Moreover, a significant increase in CRC was observed in patients on PPI monotherapy and PPI plus DOAC, suggesting a possible risk.