Taking low-dose colchicine daily may slow the progression of a common acquired gene mutation found in the blood of older adults that can lead to certain blood cancers and increased risk of cardiovascular disease, according to a subanalysis of the LoDoCo2 trial published in JACC, the flagship journal of the American College of Cardiology, and simultaneously presented at ESC Congress 2025.
Clonal hematopoiesis (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 this 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. Colchicine is a medication commonly used to treat gout and other inflammatory conditions.
Participants provided four blood samples: at the beginning of the study, after 30 days, 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. Also, two blood biomarkers of inflammation were measured at the first three timepoints.
Those 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, MPP, FACC, cardiologist at Massachusetts General Hospital and 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 Conference 2025, researchers 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 CVD 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 CVD, suggesting that CH remains associated with cardiovascular health into later life.
"Clonal hematopoiesis is emerging as a key link between aging, cardiovascular disease and cancer," said Harlan Krumholz, MD, FACC, JACC Editor-in-Chief and Harold H. Hines Jr Professor of Medicine, Yale University School of Medicine. "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."
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