The results of the COLCOT trial were presented by Dr. Jean-Claude Tardif at the American Heart Association 2019 conference and published in the New England Journal of Medicine. The study showed that in patients with a recent myocardial infarction, colchicine led to a significantly lower risk of ischemic cardiovascular events than placebo.
Previous studies have demonstrated that inflammation plays a role in the process of atherosclerosis. However, evidence surrounding whether anti-inflammatory treatment, such as methotrexate or canakinumab, can target this inflammatory pathway to reduce the incidence of cardiovascular events has been inconsistent. There is a need to identify an anti-inflammatory treatment that could potentially be used to improve outcomes in patients with cardiovascular disease. Colchicine is a potent anti-inflammatory medication that works through the inhibition of tubulin polymerization and microtubule generation. A previous trial showed that in patients with stable coronary artery disease, low dose colchicine led to fewer cardiovascular events. The investigators wanted to determine whether low dose colchicine improved cardiovascular outcomes in patients with recent myocardial infarction.
“Each and every component of the primary endpoint contributed to the composite effect in the sense that there were numerically smaller number of each of these components in the colchicine group versus placebo. That being said, the main drivers of the effect of colchicine on the composite endpoint were strokes and urgent hospitalization for angina requiring revascularization” – Dr. Jean-Claude Tarif, M.D.
The investigators enrolled 4,745 patients with a recent myocardial infarction to either placebo or colchicine (0.5mg daily) in a 1:1 ratio. Patients were eligible to be enrolled in the study if they had a myocardial infarction within 30 days of enrollment, had completed any planned revascularization procedures, and were treated according to the national guidelines. Patients were excluded if they had severe heart failure, a left ventricular ejection fraction of less than 35%, stroke within the past 3 months, or planned coronary artery bypass surgery (CABG) or a CABG within the last 3 years. The primary efficacy endpoint of this study was a composite of death from cardiovascular disease, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization.
Of the 4,745 patients enrolled in the study, 2,366 were assigned to the colchicine group and 2,379 were assigned to placebo. Patients were followed up for a median of 22.6 months and were enrolled a mean of 13.5 days after their myocardial infarction. The mean age was 60.6 years, 19.2% were women, and 20.2% had diabetes. The primary endpoint occurred in 5.5% of the colchicine group and 7.1% of the placebo group (HR 0.77, 95% CI .61 – 0.96, p = 0.02). When looking at the components of the primary endpoint, the results were as follows: Death from cardiovascular causes (HR 0.84; 95% CI 0.46 to 1.52), resuscitated cardiac arrest (HR 0.83, 95% CI 0.25 to 2.73), myocardial infarction (HR 0.91, 95% CI 0.68 to 1.21), stroke (HR 0.26, 95% CI 0.10 to 0.70), and urgent hospitalization for angina leading to coronary revascularization (HR 0.50, 95% CI 0.31 to 0.81). In an interview with Dr. Adam Phillips, a cardiologist at Beth Israel Deaconess Medical Center, Dr. Tardif discussed the effect of colchicine on the various components of the composite endpoint. Dr. Tardif said, “Each and every component of the primary endpoint contributed to the composite effect in the sense that there were numerically smaller number of each of these components in the colchicine group versus placebo. That being said, the main drivers of the effect of colchicine on the composite endpoint were strokes and urgent hospitalization for angina requiring revascularization”. With regards to colchicine’s safety profile, the incidence of adverse events that were considered to be related to either colchicine or placebo was 16.0% in the colchicine group and 15.8% in the placebo group. The most common adverse event that was significantly higher in the colchicine group was nausea. However, the incidence of pneumonia was noted to be higher in the colchicine group than the placebo group (0.9% vs 0.4%, p = 0.03).
The findings of this study suggest that a 0.5mg daily dose of colchicine could potentially improve cardiovascular outcomes in patients with recent myocardial infarction. While colchicine is a known treatment for pericarditis, this would not explain the findings of this study as this would typically occur several days after the index event (whereas the meantime from the index myocardial infarction to enrollment was 13.5 days). While the most common adverse events observed were gastrointestinal, the infection was more frequent in the colchicine group. However, the incidence of septic shock was not higher in the colchicine group (unlike the previously published canakinumab trial). While the trial demonstrates better findings with colchicine, it does have its limitations. The duration of follow up was shorter than other trials (23 months). Therefore, the risks and benefits of long term colchicine could not be evaluated. Additionally, the results of this study only apply to patients with recent myocardial infarction. However, the trial does demonstrate very promising results that support the use of colchicine.