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Low-dose prophylactic aspirin increased overall baseline gastrointestinal (GI) bleeding risk by approximately 60% in elderly users -- 87% for upper- and 36% for lower-GI bleeds -- according to a large randomized placebo-controlled trial. While the absolute 5-year risk of serious bleeding was a modest 0.25% (95% CI 0.16-0.37) for a 70-year-old not on aspirin, the risk rose to 5.03% (2.56-8.73) for an 80-year-old aspirin user who had additional risk factors, reported Suzanne E. Mahady, MD, of Monash University in Melbourne, Australia, and colleagues.

As shown in the team's study online in , risk factors for GI bleeding included advancing age (especially 80 and older), smoking, hypertension, truncal obesity, chronic kidney disease, and non-steroidal anti-inflammatory use.

The Aspirin in Reducing Events in the Elderly () study was conducted from 2010 to 2017 in 19,114 community-dwelling U.S. and Australian persons ages 70 and older, and was designed to address the lack of robust trial data on significant GI bleeding in older people on low-dose enteric-coated aspirin.

The researchers calculated the incidence, risk factors, and absolute risk, with the endpoint of major GI bleeding involving transfusion, hospitalization, surgery, or death, as determined independently by two physicians blinded to trial arms.

Over a median follow-up of 4.7 years (88,389 person-years), there were 264 clinically significant GI bleeding episodes, 137 upper-GI bleeds, 89 in aspirin users (total of 9,525 assigned to that group) and 48 in placebo recipients (9,589 individuals), for a hazard ratio of 1.87 (95% CI 1.32-2.66, P<0.01). The event rates were 2.1 per 1,000 person-years and 1.1 per 1,000 person-years, respectively.

In addition, there were 127 lower-GI bleeds overall, 73 and 54 in the aspirin and placebo arms, respectively (HR 1.36, 95% CI 0.96-1.94, P=0.08). The event rates were 1.7 and 1.3 per 1,000 person-years in the aspirin and placebo groups, respectively. Two fatal bleeds occurred in the placebo arm. Multivariable analyses indicated that age, smoking, hypertension, chronic kidney disease, and obesity increased bleeding risk in 80-year-old aspirin users with risk factors by 5.03% (range of 2.56-8.73).

The event rate for upper GI bleeding was 2.1 per 1,000 person-years in the aspirin group vs 1.1 per 1,000 person-years in the placebo group.

As for lower-GI bleeding events, 73 occurred in the aspirin group (73/9,525, 0.8%) and 54 in the placebo group (54/9,589, 0.6%), for a hazard ratio (HR) of 1.36 (95% CI 0.96-1.94, P=0.08).

There was no increase in the fatal bleeding rate in the aspirin arm, but two fatal bleeds occurred in the placebo arm. Stage 3 or higher chronic kidney disease, which affected 25% of the study population at entry, was associated with a 46% higher overall bleeding risk.

"Clinicians may use these data to assess bleeding risk, review the indication for aspirin, and target modifiable risk factors to reduce harm," the investigators wrote.

Asked for her perspective, Yamini Natarajan, MD, of Baylor College of Medicine in Houston, who was not involved with the study, noted that recent research has highlighted the limitations of widespread aspirin use for primary prevention.

"These trials, including the original ASPREE trial, led to a by the American Heart Association and the American College of Cardiology, with the new guidelines suggesting a more nuanced approach to prescribing aspirin, taking into account the risk of adverse effects such as bleeding versus the benefit of preventing cardiovascular disease," she told 番茄社区.

Since this analysis further demonstrates that aspirin increases GI bleeding in the elderly, this risk should therefore be considered before prescribing aspirin therapy, she said.

Natarajan added that further studies are needed to evaluate the risk of bleeding in patients who are taking aspirin for secondary prevention and the protective effect of proton pump inhibitors in patients who need aspirin for primary or secondary prevention. "Patients should not stop aspirin on their own," she emphasized. "They should discuss with their doctors their risks of both bleeding and cardiovascular disease and determine if aspirin therapy is appropriate for them."

In a 2018 analysis of ASPREE data, daily aspirin not only failed to help generally healthy older people reduce their risk of disability-free survival and cardiovascular disease, but also appeared to raise overall mortality, particularly death from cancer. A recent British of 13 trials of aspirin for primary prevention in mainly younger populations found a similar risk of serious GI bleeding (HR 1.56, 95% CI 1.38 -1.78).

Mahady and co-authors urged more research on how bleeding impacts patients in the long term; how it influences survival, disability-free survival, and quality of life; and how chronic kidney disease affects bleeding risk.

In the meantime, the current study "provides population-based data on GI bleeding in older populations and the impact of aspirin, providing robust and clinically meaningful estimates for use in clinical practice and future epidemiological studies," the researchers wrote.

Study limitations, they said, included the exclusion of individuals with a previous major bleeding episode or a high risk of bleeding. In addition, the uncertainty surrounding the point estimates for absolute risk illustrated by widening confidence intervals in the presence of more risk factors reflected insufficient statistical power. Future meta-analyses of bleeding events from trials may provide improved precision. Moreover, the investigators said, it was not possible to ascertain Helicobacter pylori status, which might have been useful for analyzing upper-GI bleeds. Finally, the restrictive definition of serious bleeding excluded nasal and nasopharyngeal bleeding events that may have been of significant concern to patients but did not result in hospitalization.

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