LONG-TERM USE OF ASPIRIN IS SUSTAINABLE TO REDUCE RISK OF COLORECTAL CANCER: A LONGITUDINAL STUDY OF 1,176,483 HONG KONG RESIDENTS FOR 20 YEARS

Background: Aspirin has been known for its chemopreventive effect against various cancers. Evidence for the chemopreventive effect of the very long-term use of aspirin is still uncertain. The current study aims to examine aspirin effect against colorectal cancer (CRC) over 20 years and to determine the optimal age for initiating aspirin for CRC prevention. Methods: Medical data on drug use, disease diagnosis and medical procedures were obtained from the Hospital Authority Hong Kong. Subjects aged 18 or above with aspirin use between January 2000 and June 2019 were included. Non-aspirin users were identified by age-and-gender matching as the sample population. Subjects with any cancer diagnosis, coronary heart disease or stroke prior to the index date were excluded. The index date was set at 6 months after aspirin initiation for aspirin users and the matching date for non-users. All included subjects were followed-up until June 2020. Incidence of CRC was identified as the primary outcome, while cancer-related mortality and bleeding events were identified as the secondary outcomes. The Fine-Gray model was used to calculate the sub-distribution hazard ratio (SHR), with death considered as a competing risk. Propensity score weighting stabilised with trimming was used to adjust for the difference in baseline characteristics. Concurrent medication use during the follow-up period was also adjusted in the model. Results: A total number of 250,765 aspirin users and 925,718 non-users were included in the current study. The mean age was 63.8, with 53.4% male. Forty-five percent of included subjects had hypertension at baseline, while 20% had diabetes and 20% had dyslipidaemia. Cumulative incidence functions for CRC at 20 years were 2.20% (95% CI 2.09-2.33) for aspirin users and 2.31% (95% CI 2.22-2.39) for non-users respectively. Aspirin was associated with a reduced risk of CRC (SHR 0.85, 95% CI 0.82-0.88). The optimal age to initiate aspirin for CRC prevention would be between 40-59 (aged 40-49: SHR 0.70, 95% CI 0.59-0.83; aged 50-59: SHR 0.80, 95% CI 0.73-0.87) (Figure 1). Aspirin was also shown to reduce cancer-related mortality. For bleeding events, aspirin was found to increase the risk of haemorrhagic stroke, upper and lower gastrointestinal bleeding. Conclusion: Aspirin was found to effectively reduce the risk of CRC in 20 years of follow-up. While the long-term chemopreventive effect of aspirin against CRC was certain, its benefit was more prominent in 5-10 years after aspirin initiation. The optimal time to initiate aspirin for CRC prevention can be at the age of around 40-59.