Original Research20 June 2023
A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial
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Visual Abstract. Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly

In this large primary prevention trial of aspirin in community-dwelling persons aged 70 years or older, daily low-dose aspirin increased the risk of incident anemia by approximately 20%. These findings question preventive use of aspirin in older patients and suggest caution with this practice.

Abstract

Background:

Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia.

Objective:

To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations.

Design:

Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583)

Setting:

Primary/community care in Australia and the United States.

Participants:

Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons).

Intervention:

100 mg of aspirin daily or placebo.

Measurements:

Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset.

Results:

19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results.

Limitations:

Hemoglobin was measured annually. No data were available on causes of anemia.

Conclusion:

Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin.

Primary Funding Source:

National Institutes of Health and Australian National Health and Medical Research Council.

References