Investigating the effectiveness, safety and preferences of low-dose aspirin for the primary prevention of colorectal cancer

Abstract

Aspirin is a widely used drug with multiple indications and a well-known safety profile. Colorectal cancer is the third most common cancer in the world, with more than 1.4 million new cases in 2020. The literature has pointed to the possibility of an association between low-dose aspirin use and a lower the risk of colorectal cancer; however, a number of recent studies have reported conflicting findings. Furthermore, the studies mainly included a general population without a focus on individuals who may benefit the most from low-dose aspirin use, especially those who are not routinely prescribed low-dose aspirin for the secondary prevention of cardiovascular disease. The studies also mainly represented a predominantly Caucasian population. To address these knowledge gaps, this thesis had three main objectives: (1) to evaluate the safety and effectiveness of low-dose aspirin for the primary prevention of colorectal cancer in patients without atherosclerotic cardiovascular disease in Hong Kong; (2) to evaluate the safety and effectiveness of low-dose aspirin for the primary prevention of colorectal cancer in patients with type 2 diabetes in Hong Kong and the United Kingdom; (3) to elicit the preferences of the general public and clinicians in Hong Kong on the use of low-dose aspirin for the primary prevention of colorectal cancer. The research described in this thesis utilized two large electronic health records data from Hong Kong and the United Kingdom to conduct retrospective cohort studies as well as primary data obtained from a survey representing the Hong Kong population to conduct a cross-sectional study. The main findings of the research were: (1) low-dose aspirin is associated with a lower risk of colorectal cancer in patients without established cardiovascular disease, however low-dose aspirin was also associated with an increased bleeding risk except for patients concurrently taking proton pump inhibitors or H2 receptor antagonists; (2) in patients with type 2 diabetes, low-dose aspirin was not associated with a lower risk of colorectal cancer and was associated with an increased risk of bleeding even in the subgroup of patients concurrently taking a proton pump inhibitor or H2 receptor antagonist; (3) individuals from the public valued a clinician recommendation the most when making the decision on whether to initiate low-dose aspirin for the primary prevention of colorectal cancer. A decrease in colorectal cancer risk was the second most important factor which was valued more than an increase in bleeding risk. As for clinicians, a decrease in colorectal cancer risk was valued slightly more than an increase in bleeding risk. This is the first research to evaluate the association of low-dose aspirin and the risk of colorectal cancer specifically in patients without atherosclerotic cardiovascular disease and in patients with type 2 diabetes mellitus. The findings of this research suggest that low-dose aspirin could be prescribed for the primary prevention of colorectal cancer, but only in certain individuals in which the benefits outweigh the risks. The findings also suggest that individuals who are prescribed low-dose aspirin for the primary prevention of colorectal cancer will be willing to take it.