Efficacy and safety of low-dose colchicine after myocardial infarction (COLCOT)
Selected in The New England Journal of Medicine by A. Giacaman , C. Cook
COLCOT was a double-blind RCT, designed to evaluate 0.5 mg oral colchicine daily as compared with placebo in patients within 30 days of acute myocardial infarction.
References
Authors
Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, López-Sendón J
Reference
N Engl J Med. 2019 Nov 16
Published
November 2019
Link
Read the abstractReviewers
Our Comment
This joint review is part of the PCRonline GLOBAL Journal Club Initiative by selected members of the EAPCI/PCR Journal Club and EAPCI young ambassadors, and is based on the underlying idea of “Bringing peers together, exchanging ideas, towards a common standard of care”.
Why this study – the rationale/objective?
Inflammation plays an important role in atherosclerosis, but its usefulness as a new target of treatment is not yet fully established. In the CANTOS trial, the use of canakinumab (interleukin-1β monoclonal antibody) demonstrated a reduction in cardiovascular events. However, this was also associated with a slightly higher incidence of fatal infections. Colchicine in this setting appears a potent, orally administered and inexpensive anti-inflammatory drug.
How was it executed – the methodology?
COLCOT was a double-blind RCT, designed to evaluate 0.5 mg oral colchicine daily as compared with placebo in patients within 30 days of acute myocardial infarction. 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Median follow-up was 22.6 months. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.
What is the main result?
The primary composite endpoint occurred in 5.5% of the colchicine group compared with 7.1% of the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). These results were driven mainly by less urgent hospitalizations for unstable angina leading to revascularization (1.1% vs 2.1%, HR 0.50, 95% CI 0.31–0.81, p < 0.05) and lower incidence of stroke (0.2% vs. 0.8%, HR 0.26, 95% CI 0.10–0.70, p < 0.05) in the colchicine group.
No differences in cardiovascular death or myocardial infarction were reported. The most common adverse events observed were gastrointestinal. Diarrhea (9.7% vs 8.9%, p = 0.35) and nausea (1.8% vs 1.0%, p = 0.02) occurred in the colchicine group compared with placebo, respectively. Also, an increase in the incidence of infection (2.2% vs 1.6%, p = 0.15) and pneumonia (0.9% vs. 0.4%, p < 0.05) was observed in the colchicine group.
Critical reading and relevance for clinical practice
The COLCOT trial is a pragmatic trial that delivers a clear and simple answer - among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo.
This is a ‘low-tech’ treatment approach that should prove affordable and easy to implement globally. The benefit in this trial was mainly due to a reduction in the incidence of stroke (consistently considered amongst the worst clinical outcomes by patients) and urgent hospitalization for unstable angina leading to revascularization. However, it is important to remember that despite the impressive reduction in the composite endpoint, cardiovascular death or myocardial infarction as individual endpoints were not significantly reduced.
Some caution remains in translating the trial findings into routine clinical practice. Firstly, nearly 19% of the patients in both treatment groups stopped receiving colchicine or placebo prematurely. Second, the unknown end-point status for 2.5% of the population. Lastly, concern about the increase in pneumonia as a serious adverse event in the colchicine treatment arm.
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