Key Points
- The COLCOT trial demonstrated colchicine improved coronary plaque characteristics in patients with acute coronary syndrome compared with placebo. EKSTROM sought to determine whether colchicine would reduce plaque progression in patients with stable CAD compared to placebo, as measured by coronary CTA (CCTA).
- EKSTROM randomized 84 patients with proven coronary atherosclerosis to colchicine 0.5mg or placebo. Baseline CCTA were compared with followup CCTA at 1 year. The primary endpoint was a change low attenuation plaque volume; secondary endpoints included changes in total plaque volume and other plaque characteristics.
- There was no significant difference in the rate of change of low attenuation plaque, however colchicine was associated with a significant 1.1% reduction in total plaque volume progression and also significantly slowed dense calcium progression at one year.
- This pilot study provides justification for further investigation of the impact of anti-inflammatory therapies on coronary plaque characteristics over time.
Ever since the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) demonstrated anti-inflammatory therapy could improve cardiovascular outcomes, additional research has looked into the role of using other anti-inflammatory agents, including colchicine, to improve cardiovascular outcomes in high-risk patients. A substudy of the Colchicine Cardiovascular Outcomes Trial (COLCOT) using optical coherence tomography found that colchicine resulted in favorable effects on coronary plaque stabilization.1 The impact of colchicine on coronary plaque in patients with stable coronary artery disease (CAD) is uncertain.
On March 31st 2025, results from the “Effect of Colchicine on Progression of Known Coronary Atherosclerosis in Patients with STable CoROnary Artery Disease CoMpared to Placebo – the EKSTROM Trial” were presented at ACC Scientific Sessions 2025. The purpose of this study was to evaluate whether low dose colchicine reduces plaque progression, as assessed by serial coronary computed tomography angiography (CCTA), among patients with stable CAD compared with placebo.
EKSTROM included patients aged 30-85 with CAD based on coronary angiography, CCTA, or a coronary artery calcium score of > 400 who were clinically stable for at least 6 months and had no contraindications to colchicine. Patients with NYHA class III or IV heart failure or renal impairment (eGFR < 50 ml/min 1.73 m2) were excluded. They were randomized to colchicine 0.5mg or placebo in a 1:1 fashion and underwent CCTA at baseline and 52 weeks. The primary endpoint was the rate of change in the volume of low attenuation plaque. Additional endpoints included rate of change in total plaque volume, total non-calcified plaque, and fibro-fatty, fibrous and dense calcified plaques, as well as changes in CRP.
A total of 84 patients were included in this pilot study. The average age was 65 years; 88% were male and 57% were White. Overall, 11% had diabetes, 63% had hypertension, 63% had a family history of CAD, 4.5% were smokers, and 72% were on a statin. At one year, there was no significant difference in the rate of change in low attenuation plaque volume between the two groups, which was essentially 0 for both arms. However, total plaque volume increased by 1.4% in the placebo arm vs. 0.30% in the colchicine arm, a significant difference (p=0.02). Similarly, dense calcified plaque increased by 1% in the placebo arm but only 0.1% in the colchicine arm (p=0.009). While those in the colchicine arm experienced a numerically greater decrease in non-calcified, fibro-fatty, and fibrous plaque volume, these changes were not statistically significant. CRP was significantly reduced in the colchicine arm.
Limitations included the small sample size. Furthermore, the stable CAD population enrolled had lower levels of low attenuation plaque than the ACS population in prior colchicine trials.
Matthew J. Budoff, MD, Professor of Medicine and Endowed Chair of Preventive Cardiology at UCLA, Los Angeles, California, concluded: “Low attenuation plaque was not significantly reduced, however colchicine significantly reduced total plaque volume progression by 1.1% compared to placebo at 1 year. Further, colchicine treatment demonstrated trends toward regression of non-calcified plaque, fibrous and fibro-fatty plaque, and significantly slowed dense calcium progression, and the plaque effects are independent of baseline c-reactive protein.” Multiple prespecified analyses exploring the impact of colchicine on other markers of inflammation, tissue characteristics, and endothelial function are forthcoming.