Taking low-dose colchicine daily may slow the progression of clonal hematopoiesis (CH), based on a subanalysis of the LoDoCo2 trial presented at ESC Congress 2025 and simultaneously published in JACC.

CH is an acquired mutation in blood stem cells that is linked to risk of developing leukemia and other blood cancers. It is also associated with a more than 1.5-fold increased risk of cardiovascular disease, including coronary heart disease, heart failure and arrhythmias. The most common driver genes that can lead to CH are DNMT3A, TET2 and ASXL1, which represent about 80% of CH cases. Research has shown that over 10% of people 70 years old and older carry one or more of these mutations and the risk increases with age.

In the study, researchers looked at a subset of participants in the LoDoCo2 trial, which previously found that 0.5 mg daily of colchicine reduced the risk of cardiovascular disease by 31% in people with chronic coronary disease, to determine if colchicine also modified CH growth in the same individuals. In total, 854 participants provided four blood samples at the beginning of the study, after 30 days, at one-year post randomization and at the end of the study. Their blood DNA was sequenced to detect and quantify CH mutations and analyze changes over time. Additionally, two blood biomarkers of inflammation were measured at the first three timepoints.

Results found that participants randomized to colchicine had a non-significant 6.3% annual increase in the number of overall mutated CH cells compared to a significant 14.9% increase in those taking placebo. Colchicine was associated with significantly attenuated clonal growth in TET2 CH, specifically, with a 9.1% annual increase in TET2 clone size in the colchicine group, compared with a 29.6% increase in the placebo group.

"These findings are striking in part because larger CH clones have been more strongly linked to both cardiovascular disease and cancer, and TET2 CH in particular has been consistently associated with increased cardiovascular risk," said Michael Honigberg, MD, FACC, the study's senior author. "Our study suggests that individuals with CH, especially TET2-mutated CH, may derive particular benefit from colchicine, including for cardiovascular risk reduction."

In a second study published in JACC and being presented at ESC Congress 2025, Daniel Ezzat, BSc, et al., looked at whether CH's relevance to cardiovascular disease risk decreased as women got older. Older adults have the highest risk of cardiovascular disease, and some previous studies have failed to demonstrate an association between CH and cardiovascular disease after age 70.

Researchers in this study looked at over 6,600 women in the Women's Health Initiative Long Life Study who had a median age of 80. They found that several CH subtypes (TET2, ASXL1, and JAK2) were associated with incident cardiovascular disease, suggesting that CH remains associated with cardiovascular health into later life.

In a related editorial, Shunsuke Inoue, MD, PhD, writes that findings from this study "suggest that CH may serve as a potent biomarker" in women. They note that "interventional trials targeting TET2, ASXL1, and JAK2-associated CH could offer a novel strategy to mitigate residual CVD risk."

"Clonal hematopoiesis is emerging as a key link between aging, cardiovascular disease and cancer," said Harlan Krumholz, MD, FACC, JACC Editor-in-Chief. "This study advances our understanding of how inflammation and genetic changes in blood cells may shape cardiovascular risk, pointing to new opportunities for prevention and treatment."