Aspirin Warning: Anemia May Increase With Use

Kelly Ragan

June 20, 2023

Older people who take daily low-dose aspirin have at 20% higher risk of developing anemia even without having already had a major bleeding event, according to results from a new randomized controlled trial.

In the study, which was published June 20 in the Annals of Internal Medicine, investigators analyzed data from the Aspirin in Reducing Events in the Elderly (ASPREE) and examined hemoglobin concentrations among 19,114 healthy, community-dwelling older patients.

"We knew from large clinical trials, including our ASPREE trial, that daily low-dose aspirin increased the risk of clinically significant bleeding," Zoe McQuilten, MBBS, PhD, a hematologist at Monash University in Australia and lead author on the study, said. "From our study, we found that low-dose aspirin also increased the risk of anemia during the trial, and this was most likely due to bleeding that was not clinically apparent."

Anemia is common among elderly patients. It can cause fatigue, fast or irregular heartbeat, headache, chest pain, and pounding or whooshing sounds in the ear, according to the Cleveland Clinic. It can also worsen conditions such as congestive heart failure, cognitive impairment, and depression in people aged 65 and older.

The US Preventive Services Task Force changed its recommendation on aspirin for the primary prevention of cardiovascular disease in 2022, recommending against initiating low-dose aspirin for adults aged 60 years or older. For adults aged 40 to 59 who have a 10% or greater 10-year risk for cardiovascular disease, the agency recommends that patients and clinicians make the decision to initiate low-dose aspirin use on a case-by-case basis, as the net benefit is small.

McQuilten said she spent the last 5 years designing substages of anemia and conditions such as blood cancer. In many cases of anemia, doctors are unable to determine the underlying cause, she said. One study published in the Journal of American Geriatrics Society in 2021 found that in about one third of anemia cases, the etiology was not clear.

About 50% of people older than 60 who were involved in the latest study took aspirin for prevention from 2011 to 2018. That number likely dropped after changes were made to the guidelines in 2022, according to McQuilten, but long-term use may have continued among older patients. The researchers also examined ferritin levels, which serve as a proxy for iron levels, at baseline and after 3 years.

The incidence of anemia was 51 events per 1000 person-years in the aspirin group compared to 43 events per 1000 person-years in the placebo group, according to the researchers. The estimated probability of experiencing anemia within 5 years was 23.5% (95% CI: 22.4% to 24.6%) in the aspirin group and 20.3% (95% CI: 19.3% to 21.4%) in the placebo group. Aspirin therapy resulted in a 20% increase in the risk for anemia (95% CI: 1.12 – 1.29).

People who took aspirin were more likely to have lower serum levels of ferritin at the 3-year mark than those who received placebo. The average decrease in ferritin among participants who took aspirin was 11.5% greater (95% CI: 9.3% to 13.7%) than among those who took placebo.

Basil Eldadah, MD, PhD, supervisory medical officer at the National Institute on Aging, part of the National Institutes of Health, said the findings should encourage clinicians to pay closer attention to hemoglobin levels and have conversations with patients to discuss their need for taking aspirin.

For somebody who's taking aspirin and who's older, and it's not for an indication like cardiovascular disease, consider seriously whether that's the best treatment option. Dr Basil Eldadah

"If somebody is already taking aspirin for any reason, keep an eye on hemoglobin," Eldadah, who was not involved in the study, said. "For somebody who's taking aspirin and who's older, and it's not for an indication like cardiovascular disease, consider seriously whether that's the best treatment option."

The study did not examine the functional consequences of anemia on participants, which Eldadah said could be fodder for future research. The researchers said one limitation was that it was not clear whether anemia was sufficient to cause symptoms that affected participants' quality of life or whether occult bleeding caused the anemia. The researchers also did not document whether patients saw their regular physicians and received treatment for anemia over the course of the trial.

The study was funded through grants from the National Health and Medical Research Council and the Bill and Melinda Gates Foundation. The authors reported receiving consulting fees, honoraria, and stock options and have participated on data monitoring boards not related to the study for Vifor Pharma, ITL Biomedical, Pfizer, Boehringer Ingelheim, Bayer Healthcare, AbbVie, and Abbott Diagnostics.

Ann Intern Med. Published online June 20, 2023. Abstract

Kelly Ragan is a journalist based in Greeley, Colorado.

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