Daily Low-Dose Aspirin Upped Incidence of Anemia in Older Adults

Daily low-dose aspirin increased incident anemia among otherwise healthy older adults, a secondary analysis of the randomized ASPREE trial showed.

Over a median of 4.7 years, the incidence of anemia was 51.2 events per 1,000 person-years in the aspirin group compared with 42.9 events per 1,000 person-years in the placebo group (HR 1.20, 95% CI 1.12-1.29), reported Zoe McQuilten, MBBS, PhD, of Monash University in Melbourne, Australia, and colleagues.

The estimated probability of having anemia within 5 years was 23.5% for those taking aspirin compared with 20.3% for those on placebo, they noted in the Annals of Internal Medicine.

The treatment effect was the same in the sensitivity analysis accounting for cancer incidence (HR 1.20, 95% CI 1.11-1.30), and after adjusting for characteristics associated with increased risk for anemia (adjusted HR 1.19, 95% CI 1.11-1.28).

In addition, hemoglobin levels declined by a mean 3.6 g/L per 5 years in the placebo group, while those in the aspirin group had an estimated lower baseline mean of 0.4 g/L, and experienced a steeper decline in hemoglobin over time by 0.6 g/L per 5 years compared with placebo.

And in over 7,000 participants with ferritin measures at baseline and 3 years, those in the aspirin group had greater prevalence of ferritin levels less than 45 mg/L at year 3 (13% vs 9.8% with placebo) and greater overall decline in ferritin by 11.5% versus placebo.

Of note, 3% of participants in the aspirin group experienced at least one clinically significant bleeding event compared with 2.1% of those in the placebo group.

“We knew from large clinical trials, including our ASPREE trial, that daily low-dose aspirin increased the risk of clinically significant bleeding,” McQuilten told MedPage Today in an email. “From our study we found that low-dose aspirin also increased the risk of developing anemia during the trial and this was most likely due to bleeding that was not clinically apparent.”

“In many people, anemia may have other consequences, such as fatigue and general decline in function and cognition,” she added.

The incidence of anemia is known to increase with age, and it’s estimated that about 17% of adults ages 65 and up are anemic, with a higher prevalence among people in nursing homes and hospitals.

Prior research has shown that anemia in older adults was associated with higher overall mortality, lower quality of life, higher cardiovascular disease (CVD) incidence, greater risk of falls and fractures, and longer hospital stays, while previous results from the ASPREE trial showed associations between use of low-dose aspirin and increases in overall mortality and deaths from cancer in the elderly.

The increased health risks and costs of care tied to anemia in older adults provide “further reasons to restrict the use of low-dose aspirin to those with an evidence-based indication and to monitor for development of iron-deficiency anemia in persons taking regular aspirin,” the authors wrote.

William Hung, MD, MPH, of the Icahn School of Medicine at Mount Sinai in New York City, told MedPage Today that the study’s findings show that occult blood loss and anemia are “potential harms for older adults taking aspirin for primary prevention” in addition to the known risk of major bleeding events.

“The U.S. Preventive Services Task Force already recommends against low-dose aspirin for primary prevention in older adults ages 60 and over,” he noted. “This study adds to the evidence for that recommendation.”

This post-hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial randomly assigned 19,114 participants ages 70 and older (or 65 and older for Black and Hispanic adults) in the U.S. and Australia to 100 mg of aspirin or placebo daily. Among all participants, mean age was 74, 56% were women, and 93% were white.

Risks with aspirin were consistent across sex and age, and in those with chronic kidney disease, diabetes, alcohol or tobacco use, prior aspirin use, and continued use of low-dose non-steroidal anti-inflammatory drugs and proton pump inhibitors.

McQuilten and colleagues noted that anemia may have been identified and treated by practitioners outside of the trial between annual reviews, which may have led to an underestimate of anemia incidence.