Is colchicine effective in treating atherosclerosis?

From the Guidelines

Colchicine is effective in treating atherosclerosis, particularly in reducing cardiovascular events such as myocardial infarction, stroke, and need for revascularization, as evidenced by recent clinical trials and guidelines 1.

Key Findings

• The LODOCO2 trial demonstrated that low-dose colchicine (0.5 mg daily) reduced the primary endpoint of cardiovascular death, spontaneous MI, ischemic stroke, or ischemia-driven revascularization by 31% compared to placebo 1.
• A recent meta-analysis including over 12,000 patients with atherothrombotic CAD found significantly lower risks of MI, stroke, and unstable angina-driven revascularization with colchicine treatment 1.
• The 2024 ESC guidelines recommend considering low-dose colchicine (0.5 mg daily) in patients with atherosclerotic CAD to reduce myocardial infarction, stroke, and need for revascularization, with a Class IIa and Level A recommendation 1.

Mechanism and Side Effects

• Colchicine works by inhibiting inflammation, specifically targeting the NLRP3 inflammasome pathway, which reduces the production of inflammatory cytokines contributing to plaque formation and instability.
• Common side effects include gastrointestinal symptoms such as diarrhea, nausea, and abdominal pain, with a nominal increase in non-cardiovascular death and pneumonia reported in some studies 1.

Clinical Implications

• Colchicine should be used as an adjunct to standard therapies for atherosclerosis, including statins, antiplatelet agents, and lifestyle modifications, rather than as a replacement.
• Patients with severe kidney or liver disease should use colchicine cautiously due to increased risk of toxicity.
• The benefits of colchicine in reducing cardiovascular events outweigh the risks, making it a valuable treatment option for patients with atherosclerotic CAD 1.

From the Research

Effect of Colchicine on Atherosclerosis

• Colchicine has been found to have potential in the secondary prevention of atherosclerosis due to its anti-inflammatory properties 2.
• The drug's ability to inhibit the NLRP3 inflammasome and reduce the release of inflammatory cytokines may be beneficial in preventing inflammation and limiting inflammatory injury in atherosclerosis 2, 3.
• Studies have shown that colchicine reduces the severity of atherosclerosis by inhibiting vascular inflammation, oxidative stress, platelet aggregation, and modulating autophagy 3.

Mechanism of Action

• Colchicine acts by inducing depolymerization of microtubules and inhibiting the NLRP3 inflammasome, which contributes to its anti-inflammatory effects 4, 3.
• The drug's anti-inflammatory properties may be beneficial in reducing the progression of atherosclerosis and improving cardiovascular outcomes 2, 4, 5.

Clinical Evidence

• Clinical trials have evaluated the role of colchicine in coronary artery disease, postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, and cerebrovascular disease 5.
• Low-dose colchicine has been found to reduce the occurrence of cardiovascular events in patients with chronic coronary disease and stable coronary disease 6.
• Ongoing studies are investigating the long-term tolerability and efficacy of low-dose colchicine for secondary prevention in patients with coronary disease 2, 5.