Low-dose aspirin associated with 20% increase in risk of anemia among older adults

Analysis of a randomized trial of aspirin in healthy older patients found significantly increased risk of anemia, faster decline in hemoglobin concentrations, and greater decline in ferritin levels with aspirin versus placebo.

Low-dose aspirin use was associated with increased incident anemia and faster hemoglobin decline in otherwise healthy older adults, a study found.

To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations, researchers conducted a post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial in the U.S. and Australia. Researchers randomized 18,153 community-dwelling White or Asian people ages 70 years or older and Black and Hispanic people 65 years or older to 100 mg of aspirin daily or placebo. Hemoglobin concentration was measured annually in all participants. Ferritin levels were measured at baseline and at three years in a large subset. Results were published June 20 by Annals of Internal Medicine.

Anemia incidence in the aspirin group was 51.2 events per 1,000 person-years, higher than the 42.9 events per 1,000 person-years in the placebo group (hazard ratio [HR], 1.20; 95% CI, 1.12 to 1.29). Hemoglobin concentrations declined by 3.6 g/L per five years in the placebo group. The aspirin group, which had an estimated lower baseline mean hemoglobin level by 0.4 g/L (95% CI, 0.1 to 0.7 g/L), experienced a steeper decline by 0.6 g/L per five years (95% CI, 0.3 to 1.0 g/L).

The estimated probability of experiencing anemia within five 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. The treatment effect remained unchanged in the sensitivity analysis that accounted for cancer incidence (HR, 1.20; 95% CI, 1.11 to 1.30). The effect of aspirin on risk for incident anemia was also observed after adjusting for characteristics associated with increased risk for anemia (adjusted HR, 1.19; 95% CI, 1.11 to 1.28) and was consistent across age, sex, chronic kidney disease, diabetes, smoking status, alcohol use, prior aspirin use, and use of an NSAID or proton-pump inhibitor.

In 7,139 participants with ferritin measurements at baseline and year 3, ferritin levels less than 45 mg/L at year 3 were more common in the aspirin group than in the placebo group (465 [13%] vs. 350 [9.8%]). The former also had a greater overall decline in ferritin level by 11.5% (95% CI, 9.3% to 13.7%) compared with placebo. During the study, 465 participants (2.6%) experienced at least one major bleeding event: 273 (3.0%) in the aspirin group and 192 (2.1%) in the placebo group. The total number of major bleeding events was 518 (303 in the aspirin group and 215 in the placebo group). A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results.

The researchers noted that while use of aspirin for primary prevention of cardiovascular disease is likely to decline after changes to guidelines in recent years, its long-term use will continue among the older population for secondary prevention.

“Because aspirin is typically a long-term intervention, it is likely that anemia will become progressively more frequent as treatment continues and thus indicates the need for regular measurement of hemoglobin levels among older aspirin-treated patients,” the authors wrote. “The relative effect of aspirin on anemia was consistent across subgroups and hence the absolute effect is expected to be greater in those at increased underlying risk for anemia. These risks include persons with systemic inflammatory disease or chronic renal insufficiency in whom greater attention to hemoglobin monitoring may be warranted.”