Time trend, risk and prevention of gastrointestinal bleeding in Hong Kong : a population-based study

Abstract

Gastrointestinal bleeding (GIB) is one of the most common causes of emergency visits and hospital admissions. Old age, aspirin, and Helicobacter pylori (H. pylori) infection are common risk factors for GIB, while gastroprotective agents decrease the risk of upper GIB (UGIB). Due to the ageing population, increasing use of gastroprotective agents and aspirin, and the declining prevalence of H. pylori infection, the epidemiology of GIB is rapidly changing.

In this thesis, a series of studies, mainly based on the public healthcare database of Hong Kong, were performed to evaluate the epidemiology of GIB and determine risk of GIB among specific populations. The following aspects are evaluated: 1. Trends of GIB in Hong Kong: Age- and sex-standardized incidences of UGIB and lower GIB (LGIB) from 2009 to 2018 in Hong Kong were calculated and modeled with drug prescriptions. The UGIB incidences showed a progressively declining trend. Although LGIB also had a slight decreasing trend, LGIB has surpassed UGIB, and an increasing trend was observed among those older than 80 years. 2. Seasonal variations of GIB: The analysis showed that the incidences of UGIB were higher in winter months than that in summer months with a significant 12-month seasonal pattern detected. On the other hand, the seasonal variations of LGIB were less obvious. The seasonality was particularly marked in the older population. 3. Delayed retreatment for H. pylori infection after failure of the primary treatment is associated with a higher risk of UGIB: The UGIB risk in patients who received retreatment for H. pylori was compared with that those who only received a single course of therapy. The analysis showed that there was a 1.5-fold higher risk of UGIB in patients who received retreatment, and longer delay was associated with a progressively increased UGIB risk. 4. New aspirin users showed higher GIB risk versus chronic users: Using several modeling methods, a 1.9-fold increase in the risk of GIB was observed in new aspirin users after H. pylori eradication versus chronic users. The increased risk of GIB, particularly UGIB, was more obvious in the initial 6-month treatment of aspirin. 5. Selective serotonin reuptake inhibitors (SSRIs) increase the risk of UGIB: A propensity score matching analysis was performed and found a 2-fold increase in the risk of UGIB in new users of SSRIs versus non-users after H. pylori eradication. 6. Third-generation oral P2Y12 inhibitors (ticagrelor and prasugrel) have a higher risk of GIB than clopidogrel: The meta-analysis of randomized controlled trials showed that third-generation P2Y12 inhibitors were associated with a 1.28-fold increase in the risk of GIB.

The findings in this thesis confirmed the changing epidemiology of GIB in Hong Kong and identified two new high-risk populations for GIB, including those with delay in retreatment for H. pylori and new aspirin users. Use of SSRIs or third-generation oral P2Y12 inhibitors was also found to be associated with higher risk of GIB. These findings are believed to improve the prevention of GIB.