Both acute and long-term colchicine use to treat patients with acute myocardial infarction (MI) did not reduce cardiovascular death, myocardial infarction, stroke or ischemia-driven revascularization, based on findings from the CLEAR SYNERGY trial presented during TCT 2024. The trial is the largest to date to examine the impact of colchicine in acute MI.

Researchers randomized 7,062 participants within 72 hours of PCI to either colchicine or placebo at 104 sites in 14 countries between February 2018 and November 2022. Patients were eligible if they had STEMI or large NSTEMI. Patient characteristics were similar between both groups, with a mean age was 60.6 years, 18% had diabetes and 9% had prior MI. Following initial randomization, both groups were randomized again to receive spironolactone or placebo.

At a median follow-up of three years, the composite of cardiovascular death, recurrent MI, stroke, or ischemia driven revascularization was not significantly different between the colchicine and placebo groups (9.1 vs. 9.3%, respectively). In addition, there were no significant differences in any of the individual components of the composite endpoint. However, researchers did note a significant reduction in C-reactive protein with colchicine therapy. Adverse events were similar between both groups, with the exception of diarrhea, which was more common following colchicine (10.2%) than with placebo (6.6%).

According to the study investigators, the trial was designed with 80% power to detect a 25% relative risk reduction in the primary outcome (9% estimated control event rate) as assessed using a Cox proportional hazards model, stratified by STEMI vs. NSTEMI and spironolactone vs. placebo.

"We designed this trial to provide reliable evidence of the effect of routine colchicine in acute MI on clinically important outcomes," said Sanjit S. Jolly, MD, MSc. "As the largest trial to date on this subject (649 outcome events), with significantly more events than previous studies, colchicine did not provide a significant benefit and its role in long-term post MI use is uncertain."

In a separate late-breaking study looking at colchicine use compared with placebo in 120 patients with aortic stenosis undergoing TAVR, researchers with the Co-STAR trial found that treatment with colchicine was associated with a lower risk of the primary composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker at 30 days. It was also associated with a lower incidence of >50% reduced motion or thickening of ≥1 prosthetic leaflet at 30 days.

While the Co-STAR trial was permaturely stopped due to a higher rate of strokes in patients in the colchicine group, researchers said that the "inflammatory pathway offers a potential therapeutic target to mitigate cardiac arrhythmias and subclinical leaflet thrombosis after TAVR."