Clonal haematopoiesis of indeterminate potential (CHIP), an age-related condition involving somatic mutations in haematopoietic stem cells, has been previously linked to an increased risk of cardiovascular disease (CVD).¹ However, a new secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial challenges this association in older adults and finds no evidence that aspirin provides a benefit for primary prevention in this population.²

This prespecified analysis was conducted within the ASPREE trial (NCT01038583), a double-blind, randomised, placebo-controlled study. The analysis included 9,434 community-dwelling adults in Australia and the US, aged 70 years or older, with no prior history of CVD, atrial fibrillation, or high bleeding risk. Participants were randomised to receive either 100 mg of daily aspirin or a placebo. The primary outcomes for this substudy were major adverse cardiovascular events (MACEs), including ischaemic stroke, myocardial infarction, and coronary heart disease death, and clinically significant bleeding.

At baseline, CHIP with a variant allele fraction (VAF) of ≥2% was present in 2,124 participants (23%). The analysis found that CHIP was not associated with an increased risk of MACEs (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.68–1.03). In contrast, CHIP was associated with a significantly increased risk of clinically significant bleeding (aHR, 1.24; 95% CI, 1.02–1.51). The study also investigated whether aspirin had a differential effect based on CHIP status. There was no evidence that participants with CHIP were more likely to benefit from aspirin in terms of MACE reduction or experience more harm from increased bleeding compared to those without CHIP.

These findings suggest that in an older population without established CVD, CHIP may be more of a risk marker for bleeding than for atherosclerotic events. The results do not support using aspirin for primary CVD prevention in older adults with CHIP. According to the study investigators, "The data do not provide evidence that aspirin is beneficial for older individuals with CHIP in the setting of primary prevention."² This indicates that screening for CHIP to guide primary prevention strategies with aspirin is not warranted based on this evidence.

This study was funded by the National Institute on Aging and the National Cancer Institute.

References

1. Jaiswal S, Natarajan P, Silver AJ, et al. Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. N Engl J Med. 2017;377(2):111-121. https://doi.org/10.1056/NEJMoa1701719

2. McQuilten ZK, Thao LTP, Bick AG, et al. Clonal hematopoiesis and cardiovascular disease and bleeding risk and the effectiveness of aspirin. JAMA Cardiol. Published online October 15, 2025. https://doi.org/10.1001/jamacardio.2025.3756

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