Adding colchicine after MI may reduce cardiovascular events

While a trial found that low-dose colchicine reduced cardiovascular events after myocardial infarction (MI) significantly more than placebo, there are unresolved questions about inflammation as a therapeutic target, an accompanying editorial noted.


Patients who received daily low-dose colchicine after myocardial infarction (MI) had a significantly lower risk of ischemic cardiovascular events within two years compared to those who took placebo, a randomized, double-blind trial found.

Researchers enrolled 4,745 patients within 30 days after MI (mean, 13.5 days) and randomly assigned them to receive either low-dose colchicine (0.5 mg once daily) or placebo. Most participants (93.0%) had percutaneous coronary intervention for their index MI, and most took aspirin (98.8%), a different antiplatelet agent (97.9%), and a statin (99.0%). The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. Results were published on Nov. 16 by the New England Journal of Medicine.

Overall, 2,366 patients (mean age, 60.6 years; 19.2% women) were assigned to the colchicine group, and 2,379 were assigned to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, compared to 7.1% of those in the placebo group (hazard ratio, 0.77; 95% CI, 0.61 to 0.96; P=0.02). This result was due predominantly to a lower incidence of strokes and urgent hospitalizations for angina leading to coronary revascularization. Hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for MI, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization.

The incidence of treatment-related adverse events was 16.0% in the colchicine group and 15.8% in the placebo group, and the overall incidence of serious adverse events was 16.4% and 17.2%, respectively. The most common adverse events were gastrointestinal. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P=0.35), and nausea was more common in the former than in the latter (1.8% vs. 1.0%, P=0.02). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P=0.03).

The study authors noted, among other limitations, that the duration of follow-up was relatively short and that a larger trial may have allowed a better assessment of individual end points, subgroups, and risks associated with colchicine.

Despite these results, unresolved questions remain with regard to inflammation as a therapeutic target, an accompanying editorial noted. For example, in a small subgroup of trial participants with available data, colchicine did not significantly lower the high-sensitivity C-reactive protein level more than placebo, and trials of canakinumab and methotrexate have yielded modest or null outcomes, the editorialist said.

These observations do not lessen the overall importance of inflammation in atherosclerosis, nor should they halt efforts to find more effective antiinflammatory agents with better side-effect profiles, the editorial said. However, they should encourage us to revisit whether inflammation itself is the best treatment target or whether opportunities exist to identify and better understand pathophysiological processes or mediators that incite inflammation and drive atherosclerosis in order to intervene further upstream.