Colchicine in Acute Myocardial Infarction - CLEAR SYNERGY (OASIS 9) Colchicine

Nov 17, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Population Health Research Institute, Boston Scientific
Date Presented:
11/17/2024
Date Published:
11/17/2024
Date Updated:
11/17/2024
Original Posted Date:
10/29/2024
References

Contribution To Literature:

Highlighted text has been updated as of November 17, 2024.

The CLEAR SYNERGY (OASIS 9) trial showed that in patients with acute MI undergoing PCI, daily treatment with colchicine did not reduce MACE at a median follow-up of 3 years compared with placebo.

Description:

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).

Study Design

  • International
  • 2x2 factorial randomization
  • Double-blind

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.

  • Total number of enrollees: 7,062
  • Median duration of follow-up: 3 years
  • Mean patient age: 61 years
  • Percentage female: 20%

Inclusion criteria:

  • Age ≥18 years
  • STEMI with PCI ≤12 hours since symptom onset and enrollment in SYNERGY registry
  • STEMI with PCI ≤48 hours since symptom onset and not enrolled in registry
  • NSTEMI with PCI, high-sensitivity (hs) or non-hs troponin ≥200 or ≥100 times upper limit of normal, respectively, and ≥1 of: left ventricular ejection fraction ≤45%, diabetes, multivessel disease, prior MI, or age >60 years

Exclusion criteria:

  • Current or planned use of cyclosporine, everolimus, antiretroviral protease inhibitors, azoles, or macrolides
  • Cirrhosis or other severe liver disease
  • Creatinine clearance <30 mL/min/1.73 m2
  • Serum potassium >5.0 mEq/L
  • Active diarrhea

Other salient features/characteristics:

  • Diabetes: 18%
  • STEMI: 95%
  • Median number of stents: 1.0
  • Multivessel coronary artery disease: 49%
  • Ticagrelor or prasugrel at discharge: 55%

Principal Findings:

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

  • Interaction with spironolactone assignment: p = 0.96

Secondary outcomes for colchicine vs. placebo:

  • 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 0.81-1.26)
  • LSM C-reactive protein (CRP) levels at 3 months: 2.98 vs. 4.27 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
  • Drug discontinuation: 25.9% vs. 25.5%

Interpretation:

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.

References:

Jolly SS, d’Entremont MA, Lee SF, et al., for the CLEAR Investigators. Colchicine in Acute Myocardial Infarction. N Engl J Med 2024;Nov 17:[Epub ahead of print].

Presented by Dr. Sanjit S. Jolly at the American Heart Association Scientific Sessions, Chicago, IL, November 17, 2024.

Presented by Dr. Sanjit S. Jolly at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2024), Washington, DC, October 29, 2024.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Vascular Medicine

Keywords: Colchicine, Myocardial Infarction, Mineralocorticoid Receptor Antagonists, Percutaneous Coronary Intervention, Transcatheter Cardiovascular Therapeutics, TCT24, AHA Annual Scientific Sessions, AHA24


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