Low-dose colchicine (0.5mg per day) significantly reduced the total plaque volume progression by 1.1% among patients with stable coronary artery disease compared to placebo, but failed to significantly reduce low attenuation plaque.
These are findings of the EKSTROM trial, presented during a late-breaking trial session at the 2025 American College of Cardiology (ACC) scientific session (29–30 March, Chicago, USA).
The randomised, double-blind, placebo-controlled trial evaluated the effects of low-dose colchicine (Lodoco, Agepha Pharma) on atherosclerotic plaque. A total of 84 participants were enrolled, of which 72 completed the trial, with participants randomised to receive either colchicine 0.5 mg/day or placebo (n=36 per treatment group) as add-on to their standard of care.
All participants underwent coronary computed tomography angiography (CCTA) to assess coronary artery anatomy and stenosis, at baseline and at 12 months. The primary endpoint was change in low-attenuation plaque volume, a quantification of non-calcified, lipid-rich plaque, compared to placebo as measured by CCTA.
Secondary endpoints included change in total plaque volume, and change in total non-calcified plaque, fibro-fatty, fibrous and dense calcified plaques.
The results demonstrate that low-dose colchicine significantly reduced the total plaque volume compared to placebo at 12 months (change in percent atheroma volume [PAV] was ‑1.1% between treatment groups; p=0.015), though the trial did not meet its primary endpoint, as low-attenuation plaque volume was not significantly reduced with low-dose colchicine treatment (p=0.344).
Low-dose colchicine treatment significantly reduced dense calcified plaque volume (-0.9% PAV between treatment groups; p=0.009). Similarly, low-dose colchicine treatment demonstrated trends toward regression of non-calcified plaque, fibrous and fibro-fatty plaque. Future analyses are needed in a larger population of patients to confirm these findings.
“The results from the EKSTROM trial offer powerful evidence that low-dose colchicine has potential to directly reduce inflammation, which plays a substantial role in the formation and progression of atherosclerotic plaque leading to heart disease,” said Matthew J Budoff (David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, USA). “Together with statins, antihypertensives, and other standard of care treatments, this anti-inflammatory therapy may become a vital pillar in cardiovascular disease management, and could help reduce hospitalisations and cut long-term healthcare costs.”
In his presentation at the ACC meeting, Budoff pointed out a number of limitations of the study, including that due to its funding, investigators were limited in enrolment to only 84 patients. Additionally, the stable coronary artery disease population enrolled in the trial had lower levels of both low attenuation plaque (LAP) and C-reactive protein (CRP) than prior acute coronary syndrome imaging trials using this therapy.
“The EKSTROM trial findings demonstrate that anti-inflammatory treatment with low-dose colchicine, 0.5 mg improved several measures of plaque volume changes over a period of 12 months in patients with stable coronary artery disease,” Budoff adds.
