(125) Low-Dose Aspirin and Risk of Anemia in Older Adults: Insights from a Danish Register-based Study

Background: In clinical trials, the use of low-dose aspirin (LDA) has been associated with an increased incidence of anemia, independent of major bleeding, in healthy older adults.
The widespread use of LDA for cardiovascular prevention, particularly in older populations, has raised concerns about potential adverse effects in the real world.

Objectives: To assess the correlation between LDA exposure and the risk of anemia in Danish older individuals.

Methods: This cohort study was conducted using nationwide administrative and healthcare Danish registers. The study population included LDA-naïve individuals aged 65 or older with their first LDA prescription (index date) for cardiovascular prevention between 2008 and 2013. Individuals with a history of anemia in the 5 years before or antithrombotic agent use in the 1 year before the index date were excluded. A risk-set matching approach was applied, pairing up to five controls per case based on birth year and sex. The primary outcome was anemia incidence during a five-year follow-up, defined by antianemic treatment initiation or hemoglobin values. Secondary outcomes included major bleedings. Incidence rates per 100 person-years, incidence rate ratios, and cumulative hazard functions were computed for all outcomes. Cox proportional hazards regression models were applied, adjusting for confounding factors using propensity score. Time-dependent β coefficients for LDA exposure were calculated at different follow-up periods, integrating scaled Schoenfeld residuals with time-fixed Cox regression coefficients.

Results: Among the 313 508 individuals included in the study population, those exposed to LDA (n = 59 869, 19.1%) had an incidence of 9.6% of initiating antianemic treatment, with an incidence rate ratio of 9.11 (95% Confidence Interval, CI: 8.81-9.41) compared to those non-exposed to LDA. Anemia, as determined by hemoglobin value measurements, was observed in 5.9% of exposed to LDA, with an incidence rate ratio of 7.89 (95% CI 7.58-8.21) compared to those non-exposed to LDA. Approximately one in five (n = 2422, 21.5%) among individuals with anemia, as determined by hemoglobin measurements, also experienced bleeding. Severe anemia was observed in 1.3% of those exposed to LDA compared to 0.6% of those non-exposed. Among the exposed, the decline in hemoglobin levels and the higher incidence of anemia were independent of any changes in ferritin levels.

Conclusions: These findings indicate potential associations between LDA use and the risk of anemia in older individuals in the real world. Healthcare providers should carefully evaluate the risks and benefits of LDA, underscoring the importance of continuous monitoring for anemia in LDA-prescribed older individuals.