The EKSTROM trial was a prospective, randomized, double-blinded, placebo-controlled trial investigating whether colchicine (0.5 mg/day) as an adjunct to standard care affects coronary plaque components in patients with stable coronary artery disease (CAD). The study enrolled 84 patients with proven CAD (via angiography, CT angiography, or CAC >400) who were randomized to colchicine or placebo for 12 months. The primary outcome was the rate of change in low attenuation plaque (LAP) volume measured by serial coronary CT angiography. The secondary endpoint was total plaque percent atheroma volume (PAV%). Of the 84 enrolled, 72 participants (mean age 64.6 ± 7.3 years, 88% male) completed the study. Baseline demographics, risk factors, medications, vitals, and inflammatory markers were not significantly different between groups, except the colchicine group had higher baseline use of hypertension medications (75% vs 44%). For the primary outcome, there was no significant difference in the change in total LAP between the colchicine group (median [IQR] 0.1 [-0.2, 0.2]) and placebo (0.0 [-0.2, 0.3]), with an unadjusted P = 0.342. Multivariable models adjusting for CV risk factors and baseline LAP also showed no significant difference. For the secondary outcome, follow-up total PAV at 12 months was significantly lower in the colchicine group (median [IQR] 0.3 [-0.1, 1.3]) compared to placebo (1.4 [0.4, 2.6]), with an unadjusted P = 0.008. In multivariate models, colchicine treatment remained associated with lower PAV at 1 year (P = 0.015). The study noted trends toward regression in non-calcified and fibro-fatty plaque. Inflammatory markers were reduced with colchicine but did not achieve statistical significance. Colchicine was well tolerated with no major safety concerns.
If you have stable coronary artery disease, you're likely on medications to manage cholesterol and blood pressure. But what if a simple, inexpensive anti-inflammatory drug could also help protect your arteries? A new study tested exactly that. Researchers gave 72 patients with proven heart disease either a low daily dose of colchicine or a placebo for one year, on top of their standard care. They used special heart scans to measure plaque in the arteries before and after. The results were mixed. The drug did not significantly reduce the volume of a specific, high-risk type of plaque called low attenuation plaque. However, it did make a meaningful difference in the total amount of plaque clogging the arteries, known as percent atheroma volume. Patients taking colchicine had less total plaque growth after a year compared to those on the placebo. The drug was well-tolerated with no major safety issues. This means that for people already managing their heart disease, adding colchicine might help slow down the overall progression of atherosclerosis, offering another layer of defense.
What this means for you: Colchicine slowed overall plaque growth in stable heart disease, suggesting a potential new role for this common drug.
View Original Abstract ↓
AIMS: Inflammation plays a crucial role in atherosclerosis and coronary artery disease progression. Colchicine, an inexpensive anti-inflammatory medication, has shown promising results in reducing cardiovascular events in patients with stable coronary artery disease (CAD). However, its effect on coronary plaque progression remains unclear. We investigated whether colchicine, as an adjunct to standard of care therapy, affects coronary plaque components in patients with stable CAD.
METHODS AND RESULTS: We performed a prospective, randomized, double-blinded, placebo-controlled trial in 84 patients with stable CAD to receive either colchicine (0.5 mg/day) or placebo for 12 months. All enrolled patients had proven coronary artery disease as evidenced by coronary angiography, CT coronary angiography, or a Coronary Artery Calcium Score >400. The primary outcome was the rate of change in low attenuation plaque (LAP) volume, as measured by serial coronary computed tomography angiography (CCTA), utilizing volumetric plaque quantification software at 12 months between colchicine and placebo groups. The secondary endpoint was total plaque percent atheroma volume (PAV%). The sample size was set assuming a treatment difference of at least 8 mm³ change in LAP volume in favour of colchicine compared to placebo. The mean age of the 72 participants who completed the study was 64.6 ± 7.3 years, with 63 (88%) subjects being male. Baseline demographics, risk factors, medications, vitals, and inflammatory markers were not significantly different between the colchicine and placebo groups. One exception was that the colchicine group had significantly higher use of hypertension medications (75% vs. 44%) at the study start. There was no significant difference in the change in total LAP between the colchicine group with median (IQR) 0.1 (-02, 0.2) vs. 0.0 (-0.2, 0.3) in placebo, un-adjusted P = 0.342. Multivariable models, including known CV risk factors and baseline LAP, also showed no significant difference between the changes in LAP between treatment and placebo groups. A treatment effect was observed in the total PAV%. Follow-up total PAV at 12-month scan was significantly lower at median (IQR) 0.3 (-0.1, 1.3) in the colchicine group vs. 1.4 (0.4, 2.6) in placebo, P = 0.008 (unadjusted). In multivariate models, colchicine treatment was associated with lower PAV at 1 year, P = 0.015. Trends toward regression in non-calcified and fibro-fatty plaque were observed. Inflammatory markers were reduced with colchicine, but did not achieve statistical significance.
CONCLUSION: In the EKSTROM trial, low-dose colchicine did not significantly reduce low attenuation plaque volume in patients with stable coronary artery disease over 12 months, but did achieve a significant reduction in total plaque burden (percent atheroma volume) and dense calcified plaque compared to placebo. Colchicine was well tolerated, with no major safety concerns. In this stable well-treated CAD population, LAP was rare and not significantly reduced; however, it slowed overall plaque progression, supporting further investigation of its role in secondary prevention of coronary artery disease.
EKSTROM TRIAL: NCT06342609.