Target trial emulation of aspirin after diagnosis of colorectal polyps

BACKGOUND AND AIMS: Previous research on the potential chemoprotective effect of aspirin for colorectal cancer (CRC) shows conflicting results. We aimed to emulate a trial of aspirin intiation in individuals with incident polyps. METHODS: We identified individuals registered with their first colorectal polyp in the nationwide gastrointestinal ESPRESSO histopathology cohort in Sweden. Individuals aged 45–79 years diagnosed with colorectal polyps 2006–2016 in Sweden without CRC or contraindications for preventive aspirin (cerebrovascular disease, heart failure, aortic aneurysms, pulmonary emboli, myocardial infarction, gastric ulcer, dementia, liver cirrhosis, or any other metastatic cancer) registered until the month of first polyp detection were eligible. Using duplication and inverse probability weighting, we emulated a target trial of aspirin initiation within 2 years of initial polyp detection. The main outcome measures were incident CRC, CRC mortality and all-cause mortality registered until 2019. RESULTS: Of 31,633 individuals meeting our inclusion criteria, 1716 (5%) initiated aspirin within 2 years of colon polyp diagnosis. Median follow-up was 8.07 years. The 10-year cumulative incidence in initiators versus non-initiators was 6% versus 8% for CRC incidence, 1% versus 1% for CRC mortality and 21% versus 18% for all-cause mortality. The corresponding hazard ratios were 0.88 (95% confidence interval, 95%CI = 0.86–0.90), 0.90 (95%CI = 0.75–1.06) and 1.18 (95%CI = 1.12–1.24). CONCLUSION: Aspirin initiation in individuals with polyp removal was linked to 2% lower cumulative incidence of CRC after 10 years but did not alter CRC mortality. We also observed a 4% increased risk difference of all-cause mortality at 10 years after the initiation of aspirin. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-023-01024-1.