Abstract / Summary
Abstract Background Low-dose aspirin use is associated with reduced CRC incidence and CRC-related mortality. A similar association with P2Y12 inhibitor use remains uncertain. We investigated whether the use of P2Y12 inhibitors was associated with CRC incidence and CRC-related mortality among individuals diagnosed with atherosclerotic cardiovascular disease (ASCVD). Methods From the ESPRESSO cohort, we identified 334,882 patients diagnosed with ASCVD between 2006 and 2021. We identified patients who initiated P2Y12 inhibitors ≥ 84 consecutive Defined Daily Doses (cDDDs). We estimated the risk of incident CRC and CRC mortality according to P2Y12 inhibitor use using Cox proportional-hazards regression models adjusting for potential confounders including comorbidities and regular aspirin use. Results We documented 4,015 incident CRC cases and 2,610 CRC-related deaths during a median follow-up of 5.1 years (IRQ, 2.1–9.0 years). We did not observe an association between P2Y12 inhibitor use and CRC incidence. In contrast, a longer duration of P2Y12 inhibitor use was associated with lower CRC-related mortality. Compared to non-users, multivariable-adjusted hazard ratio (HR) for CRC mortality were 0.73 (95% CI, 0.60–0.89) in patients with 336–671 cDDDs of P2Y12 inhibitor and 0.81 (95% CI, 0.68–0.97) in those with ≥672 cDDDs. Among patients with incident CRC diagnosis, subsequent initiation of P2Y12 inhibitor after CRC diagnosis was associated with significantly lower CRC mortality (HR 0.42; 95% CI, 0.29–0.60). Conclusions P2Y12 inhibitor use was not associated with risk of incident CRC but was significantly inversely associated with CRC mortality, which appeared to be due to improved survival among individuals who initiate P2Y12 inhibitors after CRC diagnosis. These findings merit further study given the observational nature of the analysis and potential for residual confounding.