Prevention & lipidsSecondary analysis
Clonal Hematopoiesis and Cardiovascular Disease and Bleeding Risk and the Effectiveness of Aspirin
- Secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomised trial
- prespecified substudy
- double-blind
- placebo-controlled
In-trial median (IQR) follow-up 4.6 (3.5-5.6) years; posttrial 8.7 (7.5-10.1) years
Authors' conclusion
In this secondary analysis of a randomized clinical trial of daily low-dose aspirin in healthy adults 70 years and older, CHIP was not associated with higher CVD risk. However, participants with CHIP had a greater risk of clinically significant bleeding. There was no evidence that participants with CHIP were more likely than those without CHIP to benefit or experience more harm from aspirin when used for primary prevention of CVD events.
Study context
- Population
- Community-dwelling adults aged ≥70 years without cardiovascular disease (CVD) event, AF, anaemia or high bleeding risk2,124 (23%) with clonal hematopoiesis of indeterminate potential (CHIP)
- Participants
- 9,434 adults
- Comparison
- CHIP vs no CHIP; aspirin vs placebo by CHIP status
- CHIP ≥10% variant allele fraction (VAF)n = 532
- Primary endpoint
- MACE (fatal and nonfatal ischemic stroke, nonfatal MI and CHD death) and clinically significant bleeding
Primary result
As reported in the abstract
MACE by CHIP status
Each group vs no CHIPAdjusted hazard ratio (95% CI)P value
CHIP 2%-10% VAF
0.84(0.68–1.03)
P = 0.09CHIP ≥10% VAF
0.80(0.57–1.12)
P = 0.19Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Aspirin vs placebo effect on MACE, by CHIP status — Aspirin vs Placebo · without CHIP | 0.91 (0.72–1.16) | |
| Aspirin vs placebo effect on MACE, by CHIP status — Aspirin vs Placebo · 2%-10% VAF | 1.40 (0.77–2.53) | |
| Aspirin vs placebo effect on MACE, by CHIP status — Aspirin vs Placebo · ≥10% VAF | 1.33 (0.52–3.37) | |
| 0.20.5125Hazard ratio (log scale) |
- Aspirin vs placebo effect on MACE, by CHIP status: heterogeneity P = .35
Safety
| Outcome | Estimate | P value | |
|---|---|---|---|
| Clinically significant bleeding by CHIP status — CHIP 2%-10% VAF vs No CHIP | aHR 1.24 (95% CI 1.02–1.51) | P = 0.03 | |
| Clinically significant bleeding by CHIP status — CHIP ≥10% VAF vs No CHIP | aHR 1.21 (95% CI 0.85–1.73) | P = 0.28 | |
| Aspirin vs placebo effect on clinically significant bleeding, by CHIP status — Aspirin vs Placebo · without CHIP | HR 1.64 (95% CI 1.22–2.30) | ||
| Aspirin vs placebo effect on clinically significant bleeding, by CHIP status — Aspirin vs Placebo · 2%-10% VAF | HR 1.45 (95% CI 0.82–2.57) | ||
| Aspirin vs placebo effect on clinically significant bleeding, by CHIP status — Aspirin vs Placebo · ≥10% VAF | HR 1.41 (95% CI 0.49–4.07) | ||
| 0.20.5125Ratio (log scale) |
- Aspirin vs placebo effect on clinically significant bleeding, by CHIP status: heterogeneity P = .91
Original publication
Clonal Hematopoiesis and Cardiovascular Disease and Bleeding Risk and the Effectiveness of Aspirin. JAMA Cardiol. Published 1 December 2025. doi:10.1001/jamacardio.2025.3756
Summarised from the published abstract; every number is checked against it