Colchicine’s Efficacy Post-MI in Question: CLEAR SYNERGY Trial Shows No Benefit

 The CLEAR SYNERGY trial has revealed surprising findings regarding the use of colchicine post-myocardial infarction (MI). This large study indicates that colchicine does not significantly reduce the risk of major adverse cardiovascular events in patients who have undergone percutaneous coronary intervention (PCI) after an acute MI.

Despite previous trials like COLCOT and LoDoCo2, which reported a 23% and 31% reduction in cardiovascular events respectively, the CLEAR SYNERGY results have raised questions about colchicine's efficacy. Lead investigator Sanjit Jolly, MD (Hamilton Health Sciences/Population Health Research Institute, Canada), expressed his surprise, noting that every analysis conducted yielded neutral results.

Jolly highlighted that the trial's findings could prompt changes in clinical practice. He emphasized the need for clinicians to reconsider the use of colchicine, especially since it was associated with side effects such as diarrhea. On a personal note, Jolly shared that he had previously prescribed colchicine for his father after an MI but has since discontinued it.

The CLEAR SYNERGY trial involved 7,062 participants and compared low-dose colchicine (0.5 mg daily) against a placebo. The primary endpoint showed no significant difference between treatment groups after a median follow-up of 3.5 years. While there were reductions in C-reactive protein levels with colchicine, this did not translate into improved cardiovascular outcomes.

Jolly speculated that the discrepancy between CLEAR SYNERGY and previous trials could be due to differences in event rates and sample sizes. He noted that earlier studies had fewer primary outcome events, while CLEAR SYNERGY had over double that number.

Guidelines from organizations like the European Society of Cardiology currently recommend colchicine for chronic coronary syndromes, but Jolly believes these guidelines may need reevaluation based on new findings.

Key Points For and Against Colchicine Use

For Colchicine:

• Previous trials, such as COLCOT and LoDoCo2, demonstrated significant reductions in cardiovascular events (23% and 31% respectively).
• A recent meta-analysis indicated that colchicine reduced the risk of ischemic stroke and major adverse cardiovascular events (MACE) in patients with prior cardiovascular issues.

Against Colchicine:

• The CLEAR SYNERGY trial found no significant difference in major adverse cardiovascular events between the colchicine and placebo groups.
• Side effects, particularly diarrhea, were more common in the colchicine group (10.2% vs. 6.6%).
• Experts suggest that the evidence from CLEAR SYNERGY provides a strong rationale against starting new patients on colchicine.
• Concerns were raised about the effectiveness of colchicine in high-risk STEMI patients with elevated inflammatory markers, suggesting it may work better in patients with lower inflammation levels.

Overall, the CLEAR SYNERGY trial raises significant questions about colchicine's role in post-MI treatment and suggests a need for further investigation into its effectiveness and safety profile.

Presented at TCT 2024