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Low-Dose Aspirin vs. Placebo on Incidence of Anemia in the Elderly
Quick Takes
- Low-dose aspirin increased the incidence of anemia in healthy older adults and was also associated with decreased ferritin levels.
- These findings were independent of major bleeding events.
- This may indicate that additional vigilance for anemia and decreases in ferritin are necessary to detect early occult blood loss when a patient is appropriately on low-dose aspirin.
Study Questions:
In community-dwelling persons ≥70 years of age (≥65 years in Black and Hispanic persons), does 100 mg of aspirin daily affect incident anemia, hemoglobin, and serum ferritin concentration?
Methods:
In the ASPREE (ASPirin in Reducing Events in the Elderly) trial, 19,114 people were randomly assigned to receive 100 mg of aspirin daily or placebo. Hemoglobin concentration was measured annually. Ferritin was measured at baseline and after 3 years in a subset of 7,139 subjects who had that test performed.
Results:
Anemia incidence in the placebo group was 42.9 events per 1,000 person-years and was 51.2 per 1,000 person-years in the aspirin group, an increase of about 20%. In the placebo group, hemoglobin declined by 3.6 g/L per 5 years. In the aspirin group, a decline that was 0.6 g/L steeper was noted at 5 years. In the subjects who had ferritin measurements at baseline and 3 years, the aspirin group had a greater prevalence of ferritin levels <45 ug/L at year 3 (13% vs. 9.8%) and a greater overall decline in ferritin by 11.5%. A sensitivity analysis quantifying the effect of aspirin that excluded major bleeding produced similar results.
Conclusions:
In otherwise healthy older patients, 100 mg of aspirin daily was associated with a decline in ferritin and an approximately 20% increased incidence of anemia.
Perspective:
Initial results of the ASPREE trial were published in 2018 and showed that aspirin, when used for primary prevention, showed a significantly higher risk of major hemorrhage, and did not result in a significantly lower risk of cardiovascular disease than placebo. At that time, about 50% of older adults were thought to be using daily aspirin for primary prevention, but that number is probably much lower now owing to changes in guidelines. Additional analysis also showed an increased all-cause mortality in the aspirin group due primarily to cancer-related deaths. That result, being different than that in previous studies (and very unexpected), has been accepted with caution and some skepticism.
Major bleeding has always been a feared consequence of prescribing aspirin. Simple anemia has been somewhat less of a concern, but in the elderly, anemia is not an entirely benign process. It can be associated with a loss of function, fatigue, disabilities, depression, and worse survival. Since most occult blood loss is likely to be from gastrointestinal (GI) sources, more GI procedures may be indicated in patients who develop an anemia from aspirin use, causing additional cost and discomfort to the patient. This is in addition to the costs and inconvenience of monitoring hematocrit and ferritin, as may now be advisable given the results of this study.
With the results of this new analysis of ASPREE data, a clinician must first ask if it is necessary to give a patient daily aspirin and to do so only when clearly indicated. Most guidelines do not recommend it for primary prevention, and these data further support those recommendations. But in the many patients for whom aspirin may have a benefit, it may now be prudent to monitor patients for anemia as well as a decreasing ferritin level, as those processes may adversely affect a patient’s overall quality of life. One might also want to exercise additional care in patients who are already anemic, or who have tended to be anemic in the past, most commonly from GI issues.
Clinical Topics: Anticoagulation Management, Dyslipidemia, Geriatric Cardiology, Prevention, Lipid Metabolism
Keywords: Aged, Anemia, Anemia, Iron-Deficiency, Anticoagulants, Aspirin, Ferritins, Frail Elderly, Geriatrics, Hemoglobins, Hemorrhage, Primary Prevention, Quality of Life
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