Low-Dose Colchicine 0.5 mg Reduced Total Plaque Volume in Stable CAD vs Placebo
Findings of the EXSTROM trial may help elucidate the mechanism by which low-dose colchicine prevents MI and stroke in adults with established CAD, experts suggest.
Low-dose colchicine (0.5 mg) (Lodoco; AGEPHA Pharma) significantly reduces total coronary plaque volume in adults with stable coronary artery disease (CAD), according to late-breaking data presented at the American College of Cardiology (ACC) 74th Annual Scientific Session and Expo (ACC.25).1
©Tefi/stock.adobe.com
The findings, from the randomized, double-blind, placebo-controlled EKSTROM trial, add to growing evidence supporting the anti-inflammatory drug’s atheroprotective role in cardiovascular disease (CVD) management, study sponsor AGEPHA Pharma said in a statement.1
Key results reported from the study include a significant reduction in total plaque volume with colchicine vs placebo over 12 months (change in percent atheroma volume [PAV] was -1.1% between groups; P =.015). Additionally, colchicine treatment significantly reduced dense calcified plaque volume (-0.9% PAV; P =.009), another indicator of CV risk, according to AGEPHA Pharma.
EKSTROM, however, did not meet investigators' primary endpoint (change in low-attenuation plaque volume [LAP], a quantification of non-calcified, lipid-rich plaque), vs placebo, which was not significantly reduced in the colchicine-treated group (P =.344). Researchers noted that limited funding restricted trial enrollment, potentially affecting the statistical power for LAP reduction.1
Nonetheless, "The results from the EKSTROM trial offer powerful evidence that low-dose colchicine (0.5 mg) has potential to directly reduce inflammation, which plays a substantial role in the formation and progression of atherosclerotic plaque leading to heart disease," Matthew J. Budoff, MD, investigator at The Lundquist Institute and professor of medicine at UCLA’s David Geffen School of Medicine, observed in the statement. "Together with statins, antihypertensives, and other standard treatments, this anti-inflammatory therapy may become a vital pillar in cardiovascular disease management, and could help reduce hospitalizations and cut long-term healthcare costs."1
The double-blind, placebo-controlled study enrolled 84 participants, with 72 completing the trial. Patients were randomized to receive either colchicine (0.5 mg daily) or a placebo as an add-on therapy to standard care. Coronary computed tomography angiography was performed at baseline and 12 months to assess plaque progression.
The findings align with prior research demonstrating low-dose colchicine’s beneficial effects on coronary plaque stability, particularly in individuals experiencing acute coronary syndrome. Data from previous trials, including those published in Circulation and JACC: Cardiovascular Imaging, suggest that colchicine can improve coronary plaque characteristics and reduce major adverse cardiovascular events (MACE), according to AGEPHA Pharma.1
"These findings are concordant with prior research that demonstrates that low-dose colchicine, 0.5 mg, improved coronary plaque stability in patients with acute coronary syndrome," Budoff added. "Taken together, these results may point to the underlying mechanism explaining how low-dose colchicine, 0.5 mg, can prevent heart attack and stroke in high-risk patients with established cardiovascular disease."1
Colchicine, 0.5 mg tablet, is the first anti-inflammatory atheroprotective treatment approved to reduce myocardial infarction, stroke, coronary revascularization, and CV death in patients with established atherosclerotic disease or multiple CV risk factors.2 Prior research indicates that a 1% difference in PAV between treatment and placebo groups corresponds to a 25% reduction in MACE risk.2
EKSTROM is the third study to demonstrate that low-dose colchicine reduces coronary plaque levels and is the first to show the effect in individuals with stable CAD, Steve Andrzejewski, AGEPHA Pharma head of US operations, commented.
The data highlight the ability of the medication to prevent "recurrent life-threatening heart-related events in people living with multiple risk factors for atherosclerotic cardiovascular disease."1
Despite the promising results, researchers emphasize the need for larger studies to confirm the findings and further explore low-dose colchicine’s role in cardiovascular care. The EKSTROM trial contributes to an expanding body of evidence suggesting that addressing inflammation may be as crucial as managing cholesterol levels in preventing cardiovascular events.1
