Aspirin increases the risk of a major GI bleeding risk by 60% in older people but the risk varies greatly depending on factors such as age and chronic kidney disease (CKD), according to the landmark ASPREE study.

The baseline risks of GI bleeding in older people should help inform decisions on treatment, according to Australian and international researchers who have further analysed data from the five year follow up of 19,114 people over age 70 randomised to prophylaxis with low-dose aspirin or control.

The main results from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, published in 2018, found there was no difference in the primary outcome of disability free survival between the 9525 people randomised to take 100mg aspirin daily and a those assigned to placebo.

In their new analysis of the data, researchers from Monash University, Melbourne, have shown that the risk of significant GI bleeding (requiring hospitalisation or transfusion) with aspirin use was increased by 87% for upper GI and 36% for lower GI bleeding.

The difference “may be explained by mechanistic differences, whereby in upper GI bleeding, aspirin induces local effects with mucosal injury with reduced mucus and bicarbonate secretion, and systemic effects of prostaglandin depletion and platelet inactivation, effects which may be synergistic,” the researchers wrote in Gut.

“Lower GI bleeding is more commonly due to a range of causes such as bleeding from diverticula with arterial rupture, angiodysplasia or haemorrhoids.”

The study found that the baseline absolute five year risk of serious GI bleeding in an otherwise well 70-year-old person not taking aspirin was around 0.25%.

Aspirin use nearly doubled the risk to 0.40%, and risk was further increased by factors such as age, smoking, hypertension, obesity, NSAID use and CKD.

GI bleeding risk was 0.60% for a person at age 80 years without aspirin and 0.96% with aspirin.  For a person with all the above risk factors the absolute five year risk of a major GI bleed was high at 2.26% and 5.03% for 70 and 80 years old, respectively.

The study investigators said it was notable that the presence of ≥stage 3 CKD was associated with a 46% higher overall bleeding risk, since about a quarter of the healthy study population over the age of 70 were in this category.

It was also notable that PPI therapy co-prescription with aspirin was not associated with lower bleeding risk in the ASPREE trial, although this may have been due to the study being  underpowered or because the observations of PPI use were observational and affected by confounding. The study also found no deaths due GI bleeding in the aspirin group, but two in the placebo group.

The study authors concluded that the ASPREE analysis provided useful population-based baseline data on GI bleeding risk in older populations and the impact of aspirin and other risk factors, to help inform treatment decisions.

“An understanding of how patients value bleeding events compared with thrombotic events avoided would be very helpful to inform benefit and risk discussions on aspirin use,” they wrote.

“The mechanism of how CKD influences bleeding risk is also important for care of people with CKD,” they added.