Update to Chapter 39: Evaluation and Management of Non-ST-Segment Elevation Myocardial Infarction and Chapter 40: ST-Segment-Elevation Myocardial Infarction

Study Summary

The COLCOT trial was a randomized, double-blind, placebo-controlled study in which the efficacy and safety of low-dose colchicine was investigated in 4,745 patients with recent myocardial infarction (MI). Patients underwent 1:1 randomization to colchicine (0.5 mg daily) or placebo; the median duration of follow-up was 22.6 months. The trial included patients who had an MI within 30 days of enrollment, had undergone planned percutaneous revascularization procedures (93% of patients), and were treated in accordance with guidelines. The primary efficacy endpoint was a composite of death from cardiovascular causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization.

The primary endpoint occurred in 5.5% of patients in the colchicine group compared with 7.1% in the placebo group (HR 0.77; 95% CI 0.61–0.96; P = 0.02). The significant reduction in the primary endpoint in the colchicine group was driven by a lower incidence of stroke and urgent hospitalization for angina leading to coronary revascularization. The study drug was well-tolerated and was associated with a similar incidence of infection and diarrhea compared with placebo.

Commentary

Study Strengths: The study was a well-conducted, randomized, double-blind placebo-controlled trial using a medication that is orally administered, inexpensive, widely available, well-tolerated, and has a low side-effect profile. The patients in this trial represented a real-world demographic group, highlighting the challenges in managing coronary disease, as demonstrated by the proportion of active smokers in the cohort (30%). Interestingly, patients were appropriately treated after the index MI, with >98% of patients prescribed aspirin, an additional antiplatelet agent, and a statin.

Study Limitations: The study was not adequately powered to allow analysis of the components of the composite primary and secondary endpoints, and a larger trial would enable individual assessment of these outcomes. The duration of follow-up was relatively short, precluding evaluation of the longer-term impact of treatment with colchicine. Additionally, only 20% of the study population were female.

Next Steps/Clinical Perspective: The COLCOT trial highlights the emerging role of anti-inflammatory pharmacotherapy after MI, and demonstrates the clinical equipoise to pursue additional trials that are larger, of longer duration, and that investigate the use of other anti-inflammatory agents. In addition, large placebo-controlled trials to investigate the long-term impact of colchicine on stable coronary artery disease would be of interest.

COLCOT builds on previous investigations into immunomodulation. The tolerance of colchicine was not associated with an increased risk of fatal infection and neutropenia compared to placebo, a finding that was demonstrated in the CANTOS trial investigating canakinumab, a monoclonal antibody targeting interleikin-1β. Similarly, the negative CIRT trial investigated the role of methotrexate in reducing levels of interleukin-1β, interleukin-6, or C-reactive protein. Put in context, COLCOT focuses attention on the value of targeting the inflammatory cascade, while seeking to strike the balance between efficacy and adverse effects from immunosuppression.

Trial Reference