Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：低剂量阿司匹林和氯吡格雷已证明对结直肠癌（CRC）具有潜在的化学预防作用。质子泵抑制剂（PPI）通常与抗凝药物一起使用，但PPI与CRC之间的关系尚不清楚。此外，直接口服抗凝剂(DOAC)下CRC风险的证据有限.本研究旨在探讨抗凝药物联合或不联合PPI对台湾CRC风险的影响。
方法：对2010年至2017年基于长贡研究数据库的1,024,227例病例进行回顾性病例对照研究。临床特征,适应症,抗凝和PPI使用的持续时间，收集CRC发生数据。采用Logistic回归校正已知的CRC风险混杂因素。
结果：氯吡格雷单药治疗可降低CRC风险（AOR0.70；95%CI0.60-0.83），而阿司匹林单独或阿司匹林加氯吡格雷均未观察到保护作用。DOAC对CRC无显著影响。PPI（AOR1.38;95％CI1.28-1.49）和PPI加DOAC（OR3.91;95％CI1.49-10.27）患者的CRC风险增加，而PPI加阿司匹林可降低CRC的风险(OR0.48;95%CI0.32-0.73)。PPI联合氯吡格雷对CRC无明显影响。
结论：这项研究表明，在所研究的台湾人群中，单独使用氯吡格雷和PPI加阿司匹林可预防CRC。在DOAC中未观察到相同的效果。此外，在PPI单药治疗和PPI加DOAC的患者中观察到CRC的显着增加，暗示可能的风险。
方法：对2010年至2017年基于长贡研究数据库的1,024,227例病例进行回顾性病例对照研究。临床特征,适应症,抗凝和PPI使用的持续时间，收集CRC发生数据。采用Logistic回归校正已知的CRC风险混杂因素。
结果：氯吡格雷单药治疗可降低CRC风险（AOR0.70；95%CI0.60-0.83），而阿司匹林单独或阿司匹林加氯吡格雷均未观察到保护作用。DOAC对CRC无显著影响。PPI（AOR1.38;95％CI1.28-1.49）和PPI加DOAC（OR3.91;95％CI1.49-10.27）患者的CRC风险增加，而PPI加阿司匹林可降低CRC的风险(OR0.48;95%CI0.32-0.73)。PPI联合氯吡格雷对CRC无明显影响。
结论：这项研究表明，在所研究的台湾人群中，单独使用氯吡格雷和PPI加阿司匹林可预防CRC。在DOAC中未观察到相同的效果。此外，在PPI单药治疗和PPI加DOAC的患者中观察到CRC的显着增加，暗示可能的风险。
