Low-Dose Aspirin Linked to 20 Percent Increase in Risk of Anemia in Healthy Elderly

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Low-Dose Aspirin Linked to 20 Percent Increase in Risk of Anemia in Healthy Elderly

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Annals of Internal Medicine: Low-Dose Aspirin Linked to 20 Percent Increase in Risk of Anemia in Healthy Elderly, Largest Study to Date

Low-dose aspirin is widely used in the primary and secondary prevention of cardiovascular diseases.

However, due to the side effects of gastrointestinal bleeding, the elderly should pay special attention when taking it and strengthen monitoring.

However, not all gastrointestinal bleeding is obvious, and occult bleeding is often difficult to be noticed.

Occult bleeding may lead to anemia through iron deficiency. It is estimated that about 30% of the elderly aged 75 and over worldwide suffer from anemia (defined by the World Health Organization: male hemoglobin <130g/L, female <120g/L) [1], and anemia in the elderly is associated with functional deficits, comorbidities, and increased risk of death [2-4].

Based on this association, an international research team led by Monash University conducted a post-hoc analysis of a randomized controlled trial they conducted, “Aspirin Reduces Clinical Events in the Elderly” (ASPREE), and they found that compared with placebo, low-dose aspirin at 100mg/day was associated with a 20% increased risk of anemia, faster decline in hemoglobin, and greater reduction in ferritin .The findings were published in the journal Annals of Internal Medicine [5].

This is the largest study to date investigating anemia in older adults.

The ASPREE trial (NCT01038583) is a double-blind randomized placebo-controlled trial that enrolled 19,114 participants from the United States and Australia between 2010 and 2014.

They were randomized at a ratio of 1:1. The trial aimed to evaluate the effect of aspirin at a dose of 100 mg/day, compared with placebo, on prolonging the disability-free lifespan of healthy elderly people aged 70 years and above (65 years and above for black American and Hispanic participants).

A total of 18,153 participants were included in the final analysis after excluding 959 participants who met WHO criteria for anemia at enrollment and 2 participants who lacked a baseline hemoglobin test result.

With a median follow-up of 4.7 years, by the end of the trial, 5.5% of participants had died, 1.2% had withdrawn, and 1.6% had been lost to follow-up.

The incidence of anemia was 51 cases per 1000 person-years in the aspirin group and 43 cases per 1000 person-years in the placebo group.

The estimated 5-year probability of developing anemia was 23.5% in the aspirin group and 20.3% in the placebo group. Aspirin resulted in a 20% increased risk of anemia compared with placebo (HR 1.20, CI 1.12-1.29).

This finding did not change in a sensitivity analysis that accounted for cancer incidence. After adjusting for anemia-related risk factors, the increased risk of anemia remained 19%.

Cumulative incidence of anemia in aspirin (dashed line) vs placebo (solid line) groups

The effect of aspirin on the increased risk of anemia was generally consistent in subgroup analyzes by age, sex, chronic kidney disease, diabetes, smoking status, alcohol consumption, history of aspirin use, and use of nonsteroidal anti-inflammatory drugs or proton pump inhibitors.

Baseline hemoglobin levels averaged 0.4 g/L lower in the aspirin group than in the placebo group and experienced a steeper decline (0.6 g/L every 5 years).

A total of 8,295 participants had serum ferritin (a protein that stores iron for the body, a commonly used detection indicator for iron-deficiency anemia) levels detected before enrollment or within 4 weeks after the start of the trial, and 7,139 of them also had ferritin detection results after 3 years.

At the third year, ferritin levels decreased by an average of 16% in the aspirin group and 3% in the placebo group, and the proportion of ferritin levels <45 μg/L and <100 μg/L was significantly higher in the aspirin group than in the placebo group (465 [13%] vs. 350 [9.8%]; 1395 [39%] vs. 1116 [31%]) .

After accounting for differences in baseline ferritin levels, the aspirin group had an average 11.5 percent greater drop in ferritin than the placebo group at year three.

Ferritin levels and proportions of <45 μg/L and <100 μg/L in the aspirin (blue) and placebo (red) groups at baseline and at 3 years of follow-up

During follow-up, a total of 465 participants (2.6%) had at least one major bleeding event, including 273 (3.0%) in the aspirin group and 192 (2.1%) in the placebo group.

A total of 518 major bleeding events occurred, including 303 in the aspirin group and 215 in the placebo group.

Sensitivity analyzes showed that major bleeding events could not explain the effect of aspirin on anemia incidence, hemoglobin decline trajectory, and ferritin levels.

Overall, post hoc analyzes of this clinical trial showed that low-dose aspirin at 100 mg/day was associated with a 20% increased risk of anemia compared with placebo, with a faster decline in hemoglobin and a greater decrease in ferritin.

The researchers suggest that the elderly who take low-dose aspirin can be regularly monitored for anemia-related indicators, but aspirin should not be stopped voluntarily without consulting a doctor.

references:

[1] Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010[J]. Blood, 2014, 123(5): 615-624.

[2] Denny SD, Kuchibhatla MN, Cohen H J. Impact of anemia on mortality, cognition, and function in community-dwelling elderly[J]. The American journal of medicine, 2006, 119(4): 327-334.

[3] Corona LP, Ande FCD, DA Silva Alexandre T, Et Al. Higher Hemoglobin Levels are associated with the ball, the : A Longitudinal Analysis [J]. BMC GERIATRICS, 2022, 22 (1): 1-9.

[4] Karoopongse E, Srinonprasert V, Chalermsri C, et al. Prevalence of anemia and association with mortality in community-dwelling elderlyly in Thailand[J]. Scientific Reports, 2022, 12(1): 7084.

[5] McQuilten ZK, Thao LTP, Pasricha SR, et al. Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly: A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial[J]. Annals of Internal Medicine, 2023.

Low-Dose Aspirin Linked to 20 Percent Increase in Risk of Anemia in Healthy Elderly

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