BENEFIT AND HARM OF ASPIRIN ON MORTALITY FROM GASTROINTESTINAL CANCERS VERSUS BLEEDING IN HELICOBACTER PYLORI-ERADICATED PATIENTS

Abstract

We investigated benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer versus excess mortality from bleeding among Helicobacter pylori (HP)-eradicated patients, and its interaction with proton pump inhibitors (PPIs). HP-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from date of HP therapy till death or end of study (July 2020). Primary exposure was aspirin use as time-varying variable. Primary outcome was GI cancer-related (gastrointestinal, hepatobiliary or pancreatic cancer) death and secondary outcome was bleeding-related (GIB or intracranial bleeding) death. Adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities and concomitant medications. Benefit-risk profile was expressed as adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and non-users. 87,967 subjects were followed for a median of 10.1years, with 1,294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR:0.51;95%CI:0.42-0.61), but higher bleeding-related mortality (aHR:1.52;95%CI:1.11-2.08). Among PPI users, aHR of bleeding-related mortality with aspirin was 1.06 (95%CI:0.70-1.63). For whole cohort, adjusted absolute risk difference between aspirin users and non-users was 7 (95%CI: 5-8) fewer cancer-related and 1 (95%CI: 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95%CI:8-10) fewer cancer-related deaths per 10,000 person-years without increase in bleeding-related deaths. GI-cancer mortality benefit from aspirin outweighs bleeding-related mortality in HP-eradicated subjects, which is further enhanced by PPI use.