Written by Peter Liu
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Colchicine therapy did not improve cardiovascular outcomes for patients with large-territory NSTEMI and STEMI but resulted in more diarrhea.
CLEAR trial muddies the waters in more ways than one…
Because inflammation clearly plays a role in atherosclerosis, medications that reduce inflammation have long had a role in the treatment of coronary artery disease (CAD). Recent trials such as COLCOT and LoDoCo2 show benefit of colchicine administration in milder MI presentations and stable CAD, respectively. This has prompted a class IIa recommendation for colchicine use in CAD in European guidelines, despite two major negative trials of colchicine (including negative cardiovascular outcomes) in atherosclerosis and stroke (CHANCE-3; CONVINCE).
Today’s featured study, the CLEAR RCT, adds to the negative trials for colchicine in CAD and atherosclerosis. This was a multicenter, randomized, placebo-controlled study using a 2×2 factorial design (spironolactone was also studied). It enrolled 7,062 patients across 14 countries with large territory NSTEMI or STEMI, comparing colchicine (0.5 mg daily) to placebo over a median follow-up of 3 years. The primary composite outcome (cardiovascular death, recurrent MI, stroke, or ischemia-driven revascularization) occurred in 9.1% of colchicine-treated patients versus 9.3% in the placebo group (HR 0.99; 95%CI 0.85–1.16; P = 0.93). Colchicine reduced C-reactive protein levels but increased diarrhea incidence (10.2% vs. 6.6%; P < 0.001). No notable differences were observed in mortality or secondary outcomes. It is possible to compare the nuanced differences between positive colchicine trials and negative colchicine trials for CAD. For example, CLEAR included much more severe MI cases than COLCOT. However, such a fastidious and meticulous approach to differentiating these trials probably misses the bigger picture: RCT results on colchicine in atherosclerotic disease have so far been mixed and inconclusive. Perhaps this is the most appropriate takeaway from the results of CLEAR.
How does this change my practice?
Taken in isolation, ESC 2024 guidelines might prompt clinicians to start colchicine indiscriminately in a large population of patients with CAD; however, due to clearly negative side effects from colchicine therapy (diarrhea) and inconsistent RCT results, I will avoid routinely prescribing colchicine for CAD for now.
Source
Colchicine in Acute Myocardial Infarction. N Engl J Med. 2025 Feb 13;392(7):633-642. doi: 10.1056/NEJMoa2405922. Epub 2024 Nov 17. PMID: 39555823
