What is the role of colchicine in patients with coronary artery disease (CAD)?

From the Guidelines

Colchicine is recommended for patients with coronary artery disease (CAD) to reduce the risk of myocardial infarction, stroke, and need for revascularization, with a suggested dose of 0.5 mg daily. This recommendation is based on the latest guidelines and clinical trials, including the 2024 ESC guidelines for the management of chronic coronary syndromes 1. The evidence suggests that low-dose colchicine has a favorable effect on cardiovascular outcomes, with a significant reduction in major adverse cardiovascular events, including myocardial infarction, stroke, and unstable angina-driven revascularization 1.

Key Points

• Colchicine's anti-inflammatory effects target the NLRP3 inflammasome pathway, which is involved in atherosclerosis progression
• The medication works by inhibiting neutrophil function and reducing inflammation in atherosclerotic plaques, which helps stabilize these plaques and prevent rupture that could lead to heart attacks
• Low-dose colchicine (0.5 mg daily) is recommended for patients with established coronary artery disease to reduce the risk of recurrent cardiovascular events
• Potential side effects of colchicine include gastrointestinal symptoms like diarrhea, nausea, and abdominal pain, and dose adjustment is necessary for patients with renal impairment

Clinical Considerations

• Colchicine should be used cautiously with certain medications like strong CYP3A4 inhibitors and P-glycoprotein inhibitors due to potential drug interactions
• The evidence for colchicine's benefit comes from clinical trials showing significant reduction in major adverse cardiovascular events in CAD patients, with the greatest benefit observed in those with recent acute coronary syndromes 1
• A recent meta-analysis including over 12 000 patients with atherothrombotic CAD has estimated the treatment effects of colchicine vs. placebo for individual outcome components, with significantly lower risks found for MI, stroke, and unstable angina-driven revascularization 1

From the Research

Indications for Colchicine in Coronary Artery Disease

The role of colchicine in patients with coronary artery disease (CAD) is based on its anti-inflammatory properties, which may help in reducing ischemic events. The indications for colchicine in CAD can be summarized as follows:

• Colchicine is approved for secondary prevention of cardiovascular events in patients with CAD, mainly based on the results of the LODOCO2 and COLCOT trials 2.
• Colchicine may be beneficial as an add-on therapy in patients who are stable or recovering from an acute event, but its efficacy may vary in patients with acute myocardial infarction already receiving intensive pharmaco-invasive therapies 2.
• The use of colchicine in post-acute myocardial infarction patients does not reduce cardiovascular or all-cause mortality, recurrent MI, or other cardiovascular outcomes, but it does not increase drug-related adverse events either 3.
• In stable coronary artery disease, colchicine has shown protective effects on surrogate outcomes, such as myocardial infarction size and postangioplasty restenosis, and may become a third pillar in the medical management of stable CAD, next to lipid regulation and platelet inhibition 4.

Efficacy and Safety of Colchicine in CAD

The efficacy and safety of colchicine in CAD have been evaluated in several studies, including:

• A systematic review and meta-analysis of randomized trials, which found that colchicine reduces the risk of myocardial infarction and stroke, but has a higher rate of gastrointestinal upset with no influence on all-cause mortality 5.
• An updated systematic review and meta-analysis of randomized controlled trials, which found that colchicine reduces the composite of adverse cardiovascular events and hospitalization urgency, but increases adverse gastrointestinal events, with no impact on all-cause mortality, cardiac arrest, stroke incidence, incidence of recurrent MI, and the levels of hs-CRP 6.

Key Findings

The key findings of the studies on colchicine in CAD can be summarized as follows:

• Colchicine may be beneficial in reducing ischemic events in patients with CAD, particularly in those who are stable or recovering from an acute event.
• The efficacy of colchicine may vary in patients with acute myocardial infarction already receiving intensive pharmaco-invasive therapies.
• Colchicine is generally safe, but may increase the risk of gastrointestinal adverse events.
• Large-scale multicenter randomized controlled trials are warranted to validate the findings and determine the optimal use of colchicine in CAD 2, 3, 4, 5, 6.