Reduction of clonal hematopoiesis mutation burden in coronary patients treated with low-dose colchicine

ABSTRACT Clonal hematopoiesis involves mutations in hematopoietic stem/progenitor cells, which increase the risk of cardiovascular disease, particularly under pro-inflammatory conditions. This study assessed the impact of the anti-inflammatory medication colchicine on clonal hematopoiesis in patients with recent myocardial infarction from the COLCOT trial. Participants were randomly assigned to low-dose colchicine (0.5 mg daily) or placebo, with 848 providing two DNA samples for longitudinal analysis. Targeted error-corrected sequencing was used, and 15,919 mutations were followed over a median period of 19.5 months. The results showed significantly lower variant allele fractions in the colchicine group compared to placebo (p interaction=0.03), with notable reductions in TET2 (10.3%, p=0.007; p interaction=0.001), TP53 (11.8%, p=0.001; p interaction=0.03), and SF3B1 mutations (19.9%, p=0.006; p interaction=0.005). Thus, colchicine reduced the proportion of clonal hematopoiesis mutations in patients with coronary disease, and longer-term studies with diverse populations are needed to confirm its potential benefits in mitigating related health risks.