Target Trial Emulation of Beta-Blockers After Diagnosis of Colorectal Polyps-Beneficial in Women

Beta-blockers are successfully used to treat hemangioma and may decrease the proliferation of cancer cells. We hypothesized that individuals with colorectal polyps may also benefit from beta-blocker initiation.

Individuals diagnosed with their first colorectal polyp 2006-2016 in the nationwide Swedish ESPRESSO histopathology cohort aged 45-79 years without CRC were eligible. We excluded individuals with previous indications for beta-blocker (cerebrovascular disease, heart failure, aortic aneurysms, myocardial infarction) and individuals with contraindications for preventive beta-blocker initiation (COPD, dementia, liver cirrhosis, Charlson score > 5 or metastatic cancer). Using duplication and inverse probability weighting, we emulated a target trial of beta-blocker initiation within 2 years of the first polyp diagnosis. Main outcomes were incident CRC, CRC mortality, and all-cause mortality until 2019.

In total, 30,399 individuals met our inclusion criteria and were followed for a median of 8 years. Beta-blockers were initiated in 2083 (6.9%) eligible individuals. The 10-year cumulative incidence in initiators versus non-initiators was 5.8% versus 8.6% for CRC incidence, 0.9% versus 1.1% for CRC mortality. The corresponding fully adjusted hazard ratios (HRs) were 0.87 (95% confidence interval, 95% CI: 0.85-0.89) and 0.96 (0.83-1.09). CRC mortality was significantly reduced in women HR 0.78 (0.68-0.99) but not in men HR = 1.14 (0.80-4.46). Cumulative CRC mortality was 0.6% in initiating women versus. 1.1% in non-initiating women.

Beta-blocker initiation within 2 years of polyp diagnosis was linked to a lower CRC incidence for all subgroups, and a lower CRC mortality in women, indicating that beta-blocker initiation may improve long-term outcomes in this high-risk population.