Background: The effect of clopidogrel, whose mechanism of action differs from that of aspirin, on CRC risk remains unknown. We investigated the effects of clopidogrel and aspirin, either as monotherapy or combined, on colorectal cancer (CRC) risk in patients with Type 2 diabetes mellitus (T2DM). Methods: We conducted a cohort study using Taiwan National Health Insurance Research Database. Four groups comprising 218,903 patients using aspirin monotherapy, 20,158 patients using clopidogrel monotherapy, 42,779 patients using dual antiplatelet therapy, and 281,840 nonuser matched controls were created using propensity score matching. Cox proportional hazards regression was used to evaluate the CRC risk during follow-up. Results: During the 13-year follow-up period, we found 9431 cases of CRC over 3,409,522 person-years. The overall incidence rates of CRC were 2.04, 3.45, 1.55, and 3.52 per 1000 person-years in the aspirin, clopidogrel, dual antiplatelet, and nonuser cohorts, respectively. The adjusted hazard ratios (aHRs) were 0.59 (95% confidence interval [CI], 0.56-0.61), 0.77 (95% CI, 0.68-0.87), and 0.37 (95% CI, 0.33-0.40) for the aspirin, clopidogrel, and dual antiplatelet cohorts, respectively. Dose- and duration-dependent chemopreventive effects were observed in the three cohorts.
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