Reference
Roubille F, Bouabdallaoui N, Kouz S, et al. Low-dose colchicine in patients with type 2 diabetes and recent myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Diabetes Care. 2024;47(3):467-470.
Study Objective
To determine if low-dose colchicine affected rates of ischemic cardiovascular events in patients with type 2 diabetes who had a myocardial infarction (MI) within the last 30 days
Key Takeaway
Low-dose colchicine significantly reduces risk of ischemic events in patients with type 2 diabetes following myocardial infarction.
Design
Randomized, double-blind, placebo-controlled trial
Participants
The study included 959 patients with type 2 diabetes who experienced a myocardial infarction in the last 30 days. The mean age of participants was 62.4 years (22.2% women). Study took place in 167 centers across 12 countries.
Participants were excluded for a variety of reasons including class 3 or 4 heart failure, left ventricular ejection fraction < 35%; stroke within the past 3 months, type 2 index MI, coronary bypass surgery within the past 3 years or planned, history of noncutaneous cancer within the last 3 years, inflammatory bowel disease or chronic diarrhea, neuromuscular disease, or nontransient creatine phosphokinase greater than 3 times the upper limit of normal (ULN), significant nontransient hematological abnormalities, severe renal disease with serum creatinine greater than twice the ULN, severe hepatic disease, drug or alcohol abuse, chronic systemic steroid therapy, or history of sensitivity to colchicine.
Intervention
The active group received 0.5 mg of colchicine once daily, while the control group received a placebo of undisclosed ingredients once daily.
Study Parameters Assessed
Investigators monitored participants for 22.6 months (median duration) for ischemic cardiovascular events and side effects of medication. They performed clinical evaluations every 3 months but did not statistically evaluate and publish an aggregate biochemical assessment.
Primary Outcome
The primary outcome of the study was a cardiovascular event that included cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. A total of 8.7% of participants receiving colchicine experienced such an event, whereas 13.1% of participants in the placebo group met the end point.
Key Findings
Participants with type 2 diabetes receiving 0.5 mg of colchicine daily following a myocardial infarction experienced significantly fewer major ischemic cardiovascular events than those in the placebo group (0.65 HR; 95% CI, 0.44–0.96; P=0.03). This represents a risk reduction of 35%.
Transparency
The study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and undisclosed philanthropic foundations. Disclosures were stated by authors. One author waived rights to a patent for the use of colchicine after myocardial infarction.
Practice Implications & Limitations
Inflammation plays a pivotal role in the initiation, progression, and destabilization of atherosclerosis. Chronic inflammation can lead to endothelial dysfunction, characterized by impaired vascular homeostasis and increased permeability.1 This dysfunction allows for the entry of lipids and immune cells into the arterial wall, initiating the formation of atherosclerotic plaques, recruitment and activation of immune cells, particularly macrophages and T lymphocytes, within the arterial wall, and instability by releasing proteases that degrade the extracellular matrix and weaken the fibrous cap covering the plaque. Plaque rupture or erosion can lead to thrombus formation and acute cardiovascular events, such as myocardial infarction or stroke.
Individuals with type 2 diabetes are at higher risk of presenting with a cardiovascular event after a myocardial infarction compared to nondiabetic patients.2
Colchicine is a prescription medication derived from the Colchicum autumnale plant. While mostly known for its use acutely and prophylactically for gout and arthritis, it also has use for familial Mediterranean fever (FMF). Colchicine works by disrupting microtubule formation, inhibiting neutrophil migration and activation, and reducing the inflammatory response and potentially other anti-inflammatory mechanisms.3 It is commonly dosed in 0.6-mg increments, such as 1.2 mg per day for gout prophylaxis, 1.2 mg followed by 0.6 mg an hour later for acute gout exacerbations, and off-label use for pericarditis at 0.6 mg once or twice daily.4 However, colchicine has lost favor to nonsteroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids for acute gout exacerbations and to urate-lowering allopurinol, a xanthine oxidase inhibitor, for prophylaxis.5
Individuals with type 2 diabetes are at higher risk of presenting with a cardiovascular event after a myocardial infarction compared to nondiabetic patients.
Colchicine has garnered interest for a variety of uses, including cardiovascular medicine, over the last decade.6 Developing and compelling research has found new uses for colchicine, associated with its inhibition of endothelial inflammation via the NLRP3/C-reactive protein (CRP) pathway, as seen presenting as leukocytosis.7 Colchicine (0.5 mg daily) reduced cardiovascular risk in patients with chronic coronary artery disease as demonstrated in the Low-Dose Colchicine 2 (LoDoCo2) trial.8 A systematic review and meta-analysis found that colchicine users had lower risk of major adverse cardiac events (P<0.001) and significantly reduced high-sensitivity CRP (–4.25, P<0.001).9
This study evaluating colchicine in patients with type 2 diabetes following a myocardial infarction is consistent with a previous trial on a more general population following myocardial infarction that also found that 0.5 mg of colchicine reduced ischemic events when implemented within 30 days of the first event as compared to placebo.10 It is worth noting that implementation was swift, and patients began colchicine on average of 14 days following myocardial infarction in addition to their prescribed discharged or continued polypharmacy cocktail, which often consisted of medications such as aspirin, another antiplatelet agent, a statin, and a beta-blocker as well as typical diabetes management medications.
Despite its potential benefits, colchicine is associated with several side effects, including gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain. These side effects may limit its tolerability. Increased rates of nausea and pneumonia were seen in this low-dose trial, which warrants monitoring if colchicine is selected as a treatment. Colchicine impairs neutrophil recruitment and migration, which is 1 theory as to the increased immune compromise.
While not subjected to the same rigor in clinical trials as colchicine, other natural compounds that act on the NLRP3/CRP pathway have intriguing preliminary evidence. Curcumin, resveratrol, quercetin, omega-3 fatty acids, vitamin D, and berberine are candidates for supporting inflammation specific to this pathway.11-16 However, dosing strategies and outcome measures are not available for comparison between these supplement options and low-dose colchicine.
