Risk of anaemia increased among elderly patients taking low-dose aspirin

26th June 2023

The risk of anaemia is higher among patients aged 70 years and older taking a daily dose of 100 mg of enteric-coated aspirin, according to a post hoc analysis of the ASPREE randomised controlled trial.

The Aspirin in Reducing Events in the Elderly (ASPREE) trial was designed to examine whether a daily dose of 100 mg of aspirin would prolong the healthy life span of older adults. While it is recognised that aspirin use in patients without cardiovascular disease lowers the risk of cardiac events but increases the risk of a major bleed, whether aspirin use also associated with anaemia is less certain.

Details of the ASPREE trial have been already published and revealed a higher all-cause mortality, largely due to cancer-related deaths, in those assigned to daily aspirin compared to placebo.

In the post hoc analysis of the ASPREE trial, published in the Annals of Internal Medicine, researchers investigated the effect of low-dose aspirin on incident anaemia, haemoglobin and serum ferritin concentrations.

Researchers assessed haemoglobin levels annually and ferritin levels at both baseline and after three years. The primary outcome was defined as incident anaemia but researchers also considered changes in haemoglobin and ferritin levels over time.

Aspirin use and anaemia

A total of 18,153 participants with a mean age of 74 years (44% male) were included, of whom 9,047 were randomised to a daily dose of 100 mg of enteric coated aspirin. Participants were followed for a median of 4.7 years after randomisation.

The incidence of anaemia was significantly higher in the aspirin group (hazard ratio, HR = 1.20, 95% CI 1.12 – 1.29). In addition, haemoglobin concentrations declined more steeply in those assigned to aspirin.

By year three, serum ferritin levels had reduced by an average of 11.5% in the aspirin group compared to those assigned to placebo. A higher proportion of patients assigned to aspirin experienced a major bleeding event compared to placebo (3% vs 2.1%). However, in sensitivity analysis, this difference did not account for the levels of anaemia seen between the two groups.

Overall the results suggested that the risk of developing anaemia within five years was 23.5% among those taking low dose aspirin.

Low-dose aspirin use linked to increased risk of serious falls in elderly

18th November 2022

An RCT has found that low-dose aspirin use failed to reduce fracture risk but was associated with higher risk of serious falls in the elderly

Daily low-dose aspirin (100 mg) given to healthy elderly patients failed to reduce the risk of fractures but did increase the risk of a serious fall according to the findings of a randomised, placebo-controlled trial by Australian researchers.

In a 2017 study it was found that, globally, falls resulted in 695,771 deaths and more than 95% of hip fractures are caused by falling. Low-dose aspirin is often taken by elderly patients with cardiovascular disease although interestingly, there is some evidence to suggest that aspirin inhibits osteoclastogenesis by suppressing the activation of NF‑κB and therefore may possess therapeutic potential for use in the prevention and treatment of osteoporosis.

By inhibiting osteoclasts, aspirin may increase bone mineral density and therefore reduce the risk of fractures. In fact, a systematic review of 12 observational studies found that aspirin use was associated with 17% lower odds for any fracture. Nevertheless, to date, no randomised, placebo-controlled trials have examined the potential role of low-dose aspirin as an approach to reduce fracture risk among older adults.

In the present study, the Australian researchers created the ASPREE-FRACTURE study which was actually a sub-study of the Aspirin in Reducing Events in the Elderly trial designed to examine if daily low-dose aspirin use outweigh the risks in older healthy individuals. Participants in the trial received low-dose aspirin (100 mg daily) or matching placebo and the primary outcome was the occurrence of any fracture whereas the secondary outcome was set as a serious fall that resulted in hospital presentation. All participants were free of cardiovascular disease, dementia or physical disability at the start of the study.

Low-dose aspirin and fracture outcomes

A total of 16,703 individuals with a median age of 74 years (55% female) were recruited and randomised to either aspirin (8,322) or placebo and followed-up for a median of 4.6 years.

During follow-up there was no difference in the risk of first (hazard ratio, HR = 0.96, 95% CI -087 – 1.06, p = 0.50) or recurrent (HR = 0.96, 95% CI 0.87 – 1.06, p = 0.40) fracture events. In subgroup analysis based on several factors such as gender, body mass index or frailty, there were no significant differences in the risk of a first fracture event.

However, when researchers looked at the secondary out, 9% of those receiving aspirin compared to 8.2% in the placebo arm, experienced a serious fall, indicating that use of low-dose aspirin used was associated with a significant increase in the risk of such falls (HR = 1.17, 95% CI 1.03 – 1.33, p = 0.01).

The authors concluded that the use of low-dose aspirin provides little favourable benefit in a healthy, older adult population.

Citation
Barker AL et al. Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial. JAMA Intern Med 2022.