Historical collection · First published Nov 17, 2024; added to EM Weekly Oct 28, 2026. This retrospective summary may be superseded by later evidence or guidance.
← All articlesColchicine in Acute Myocardial Infarction
Summary
CLEAR SYNERGY used a blinded 2-by-2 factorial design and randomized 7,062 patients with acute myocardial infarction at 104 centers in 14 countries to colchicine or placebo, with an independent spironolactone allocation. Over a median 3 years, the primary composite of cardiovascular death, recurrent MI, stroke, or unplanned ischemia-driven revascularization occurred in 322/3,528 (9.1%) with colchicine versus 327/3,534 (9.3%) with placebo (HR 0.99, 95% CI 0.85–1.16; P=0.93). Colchicine lowered CRP at 3 months but increased diarrhea (10.2% vs 6.6%); serious infections were similar.
Why it matters
Routine colchicine started soon after an index MI did not improve major cardiovascular outcomes in this large contemporary trial, arguing against assuming benefit from indiscriminate initiation during the acute MI hospitalization. Later ACS guidance still treats low-dose colchicine as an optional secondary-prevention strategy based on the broader evidence base, so CLEAR should not be interpreted as proving that colchicine has no post-ACS role.
Study at a glance
- Design
- Randomized trial
- Population
- Adults with acute myocardial infarction treated in a contemporary post-PCI setting at 104 centers in 14 countries.
- Sample size
- 7062
- Intervention
- Colchicine versus matching placebo; official trial-registry material identifies 0.5-mg colchicine tablets and the regimen was modified during the trial.
- Comparator
- Matching placebo.
- Primary endpoint
- Time to cardiovascular death, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization.
Main findings
- Primary endpoint: 322/3,528 (9.1%) with colchicine versus 327/3,534 (9.3%) with placebo; HR 0.99 (95% CI 0.85–1.16), P=0.93.
- Adjusted 3-month CRP was lower with colchicine by 1.28 mg/L (95% CI 0.75–1.81 lower).
- Diarrhea occurred in 10.2% versus 6.6% (P<0.001); serious infections did not differ.
Limitations
This was predominantly a post-PCI STEMI population and evaluated long-term secondary prevention rather than an immediate ED endpoint. The colchicine regimen was modified during the trial, and the neutral result should not be extrapolated to every chronic coronary-disease population or timing strategy.
Read the primary source
Full text: Open-access full text available.
Original sourcePMID: 39555823
Material reviewed: abstract.
Source retrieved Oct 28, 2026. Historical backfill. NEJM publisher metadata and PubMed verify online publication on 2024-11-17, DOI 10.1056/NEJMoa2405922, PMID 39555823, and free-article availability. The publisher abstract and official EU trial-registry metadata were reviewed; this record does not claim end-to-end full-text review. Targeted title/DOI checking found no correction or retraction. As later context, the 2025 ACC/AHA/ACEP/NAEMSP/SCAI ACS guideline gives low-dose colchicine after ACS a Class 2b, LOE B-R recommendation, so this neutral trial is not presented as superseding the broader evidence base.
Corrections & review history
No corrections recorded. Human review: not yet human-reviewed.