Dr. Berkant Öztürk, Dr. Mustafa Yenerçağ

Name of the study:
CLEAR SYNERGY (OASIS 9): Early and Long-Term Colchicine After Acute Myocardial Infarction

Published in Congress: TCT 2024, Presenter: Sanjit Jolly

Link: https://www.tctmd.com/news/colchicine-surprise-no-help-post-mi-large-clear-synergy-trial-shows

Introduction:
The routine use of colchicine, an anti-inflammatory agent with a challenging side-effect profile, fails to reduce the risk of major adverse cardiovascular events when used in patients treated with PCI after acute myocardial infarction, results from the CLEAR SYNERGY (OASIS 9) trial show.

Objective:
The goal of the trial was to determine the long-term cardiovascular (CV) effects of colchicine following percutaneous coronary intervention (PCI) for ST-segment elevation or large non–ST-segment elevation myocardial infarction (STEMI or NSTEMI, respectively).

Methods:
Patients with acute MI were randomized in 1:1 fashion to receive colchicine 0.5 mg (n = 3,528) or placebo (n = 3,534) following PCI, preferably with the Boston Scientific SYNERGY everolimus-eluting platinum chromium stent system. Colchicine dosing was changed from weight-based (daily for <70 kg, twice daily for ?70 kg) to daily during the trial due to increased rates of discontinuation with twice daily dosing. Each arm was further randomized to receive spironolactone 25 mg daily or placebo. The current data compare the colchicine and matching placebo arms irrespective of spironolactone use.
Study Design: International multicenter, 2x2 factorial randomization, Double-blind

Results:
The primary outcome of major adverse CV events (MACE), composite of CV death, MI, stroke, or ischemia-driven revascularization, for colchicine vs. placebo at 5 years, was: 9.1% vs. 9.3%, hazard ratio (HR) 0.99 (95% confidence interval [CI] 0.85-1.16), p = 0.93.
Secondary outcomes for colchicine vs. placebo at 5 years:

• CV death: 3.3% vs. 3.2%, HR 1.03 (95% CI 0.80-1.34)
• All-cause death: 4.6% vs. 5.1%, HR 0.90 (95% CI 0.73-1.12)
• MI: 2.9% vs. 3.1%, HR 0.88 (95% CI 0.66-1.17)
• Ischemia-driven revascularization: 4.6% vs. 4.7%, HR 1.01 (95% CI 0.81-1.17)
• C-reactive protein (CRP) levels at 3 months: 3.0 vs. 4.3 mg/dL, p < 0.001

Safety outcomes for colchicine vs. placebo:

• Diarrhea: 10.2% vs. 6.6%, p < 0.001
• Serious infection: 2.5% vs. 2.9%, p = 0.85

Conclusions:
The CLEAR SYNERGY (OASIS 9) trial showed that in patients with acute MI undergoing PCI, daily treatment with colchicine did not reduce MACE at 5 years compared with placebo.

Comment:
Several randomized trials, including the COLCOT trial of 4,745 patients following acute MI, have demonstrated reductions in MACE with colchicine in the treatment of coronary artery disease. The current data represent the largest randomized assessment of colchicine in acute MI and failed to demonstrate a reduction in MACE or its component endpoints with extended follow-up to 5 years. Colchicine’s reported effects on these endpoints, including repeat MI, urgent revascularization, and stroke, have varied across studies but were identical to placebo in CLEAR SYNERGY (OASIS 9). Although population differences between COLCOT, which was performed in Quebec, and this international study are possible, no treatment interactions by region were observed. A signal for increased non-CV death in a prior meta-analysis of colchicine trials was reassuringly not observed here. Overall, these findings suggest that routine colchicine use following PCI for acute MI is not beneficial.