337 MAJOR GASTROINTESTINAL BLEEDING IN OLDER PERSONS USING ASPIRIN:INCIDENCE AND RISK FACTORS IN THE ASPREE RANDOMIZED CONTROLLED TRIAL

Background Aspirin is widely known to cause serious gastrointestinal bleeding, but there is little data to assist prediction of individuals at the highest risk, and no trial based data from older people. We assessed the incidence and risk factors for bleeding with aspirin in a large, community-based, randomized trial. Methods We examined data from an aspirin primary prevention trial (ASPREE, n=19,114) where people 70 years or older (65 years for U.S. minorities) were randomized to aspirin or placebo. Baseline clinical characteristics were collected annually and gastrointestinal bleeding events were standardized and adjudicated by a physician panel. We calculated the incidence of upper and lower gastrointestinal bleeding, used Cox regression analyses to identify predictors, and modelled the absolute risk of bleeding according to age and risk factors. Results Of 19,114 participants, 9525 and 9589 were randomized to aspirin and placebo respectively, with total follow of 88,389 person years. There were 264 serious gastrointestinal bleeding events, where 137 were upper gastrointestinal (89 in aspirin arm and 48 in placebo arm, HR 1.87 95% CI 1.32-2.66, p<0.01) and 127 were lower gastrointestinal events (73 in aspirin arm and 54 in placebo arm, HR 1.36, 95% CI 0.96-1.94, p=0.08) (Figure 1). Multivariate analyses indicated that age, smoking, chronic kidney disease and NSAID use were risk factors for upper gastrointestinal bleeding, while age, smoking, and hypertension were risk factors for lower gastrointestinal bleeding. Proton pump inhibitor use was not associated with reduced bleeding events. The absolute, 5 year serious bleeding risk was 0.2% for 70 year olds and 0.4% if on aspirin, and up to 5.5% for 80 years with aspirin and significant risk factors (Figure 2). Conclusion In older people, aspirin approximately doubles the risk of serious upper gastrointestinal bleeding, which further increases with age, smoking, chronic kidney disease and NSAIDs. Proton pump inhibitor therapy did not reduce bleeding risk. These data may help identify those at highest risk of bleeding and assist decision making on aspirin use for prophylaxis of vascular events and bowel cancer chemoprevention.