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Cautionary Alert: Updated Warning Regarding Low-Dose Aspirin

According to findings from a recent randomized controlled trial published in the Annals of Internal Medicine on June 20, older individuals who regularly take low-dose aspirin face a 20% higher risk of developing anemia, even if they haven’t experienced any major bleeding events. The study, which examined data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, focused on hemoglobin concentrations among 19,114 healthy older adults living in the community.

Lead author of the study, Dr. Zoe McQuilten, a hematologist at Monash University in Australia, acknowledged that previous large-scale clinical trials, including ASPREE, had already established that daily low-dose aspirin increases the risk of significant bleeding. However, this new research discovered that low-dose aspirin also heightened the risk of anemia during the trial, likely due to bleeding that went unnoticed from a clinical perspective.

Anemia is a prevalent condition among elderly patients and can manifest with symptoms such as fatigue, rapid or irregular heartbeat, headaches, chest pain, and pulsating or whooshing sounds in the ears. The Cleveland Clinic notes that anemia can also exacerbate existing conditions such as congestive heart failure, cognitive impairment, and depression in individuals aged 65 and older. It’s important for healthcare professionals to consider these potential risks when prescribing low-dose aspirin to older patients and to closely monitor their hematological health.

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.

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Dr. Oche Otorkpa PG Cert, MPH, PhD

Dr. Oche is a seasoned Public Health specialist who holds a post graduate certificate in Pharmacology and Therapeutics, an MPH, and a PhD both from Texila American University. He is a member of the International Society of Substance Use Professionals and a Fellow of the Royal Society for Public Health in the UK. He authored two books: "The Unseen Terrorist," published by AuthorHouse UK, and "The Night Before I Killed Addiction."
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