Colchicine prevents cardiovascular events

Low-dose colchicine in patients with a recent myocardial infarction (MI) can prevent major adverse cardiovascular (CV) events compared with placebo by a 28% margin. The benefit was primarily attributable to a lowered incidence of stroke or urgent hospitalisation for unstable angina leading to revascularisation in patients, according to the COLCOT trial presented by Prof. Jean-Claude Tardif (University of Montreal, Canada) [1].

Although the smaller LoDoCo trial previously showed that 0.5 mg colchicine reduced the risk of CV events in the setting of stable coronary artery disease, suggestive of a benefit, it was limited by the lack of a placebo comparator. To address the value of low-dose colchicine (0.5 mg once daily) in patients with a recent history of MI, the COLCOT trial randomised 4,745 patients (mean age 60.6 years; 19.2% female) in 12 countries to either colchicine or placebo. Patient characteristics in both groups were similar, with trial entry being a mean of 13.5 days post-MI in both groups.

The primary efficacy endpoint —a composite of death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalisation for angina requiring revascularisation— was met; at a median follow-up of 22.6 months, the proportion of patients receiving colchicine who experienced a primary-endpoint event was significantly lower than those who received placebo (5.5% vs 7.1%; HR 0.77; 95% CI 0.61-0.96; P=0.02; see Figure). Analysing the individual components of the primary endpoint revealed no significant differences in CV death, resuscitated cardiac arrest, or MI between the 2 study arms. However, the secondary composite endpoint of CV death, cardiac arrest, MI, or stroke was not significantly altered by colchicine treatment (HR 0.85; 95% CI 0.66-1.10). The results were simultaneously published in the New England Journal of Medicine [2].

Figure: Primary efficacy endpoint (i.e. CV death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalisation for angina requiring revascularisation) in ITT population. Modified from [2]



Serious adverse events were equally common overall between the 2 study arms, though pneumonia was more common with colchicine than with placebo (0.9% vs 0.4%; P=0.03), as was nausea (1.8% vs 1.0%; P=0.02). Drug discontinuation did not differ between colchicine and placebo users. The relatively short median follow-up of 23 months precludes the ability to draw firm conclusions regarding the long-term safety and efficacy of colchicine. However, the broad access and affordability of colchicine, as well as renewed interest in treating inflammation for secondary prevention after MI, make this study particularly notable.

1. Tardif J-C, et al. The COLchicine Cardiovascular Outcomes Trial (COLCOT). LBS01, AHA Scientific Sessions 2019, 14-18 November, Philadelphia, USA.
2. Tardif J-C, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med. 2019 [Epub ahead of print].

Posted on 26 February 202031 January 2024