CLEAR SYNERGY Finds Routine Colchicine Administration After Acute MI Did Not Improve Outcomes

October 29, 2024—Results from the CLEAR SYNERGY trial showed that both acute and long-term use of colchicine—an oral medication that reduces inflammation—did not reduce cardiovascular death, myocardial infarction (MI), stroke, or ischemia-driven revascularization.

The CLEAR SYNERGY findings were presented at TCT 2024, the 36th annual Transcatheter Cardiovascular Therapeutics annual scientific symposium of the Cardiovascular Research Foundation held October 27-30 in Washington, DC.

According to the TCT press release, the CLEAR SYNERGY (also identified as OASIS 9) used a placebo-controlled factorial design and is the largest trial of colchicine in patients with acute MI. Smaller studies had indicated potential benefits of colchicine for cardiovascular patients. Inflammation may play an important role in acute coronary syndromes and coronary artery disease.

As summarized in the TCT press release, CLEAR SYNERGY trial enrolled 7,062 patents at 104 sites in 14 countries between February 2018 and November 2022. Patients were eligible if they had ST-segment elevation myocardial infarction (STEMI) or large non-STEMI (NSTEMI). Patient characteristics included mean age, 60.6 years; diabetes, 18%; and previous MI, 9%.

Patients were randomized to either colchicine or placebo within 72 hours of percutaneous coronary intervention. Then, both groups were randomized again to receive spironolactone or placebo. Patient characteristics were similar between both groups.

The TCT press release explained that 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 versus NSTEMI and spironolactone versus placebo.

As reported in the TCT press release, at a median follow-up of 3 years, the CLEAR SYNERGY investigators found:

• 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%; HR, 0.99; 95% CI, 0.85-1.16; P = .93).
• There were no significant differences in any of the individual components of the composite endpoint.
• There was a significant reduction in C-reactive protein, a marker for inflammation, observed with colchicine therapy.
• Adverse events were similar between both study cohorts except that diarrhea was more common after colchicine than with placebo (10.2% vs 6.6%; P < .001).

Sanjit S. Jolly, MD, who is principal investigator of the study, commented on the findings in the TCT press release. Dr. Jolly is a scientist at the Population Health Research Institute, a joint institute of McMaster University and Hamilton Health Sciences, in Hamilton, Canada.

“We designed this trial to provide reliable evidence of the effect of routine colchicine in acute myocardial infarction on clinically important outcomes,” stated Dr. Jolly. “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 myocardial infarction use is uncertain.”