Is colchicine effective for treating coronary artery disease?

Colchicine for Coronary Artery Disease

Low-dose colchicine (0.5 mg daily) should be considered in patients with atherosclerotic coronary artery disease to reduce the risk of myocardial infarction, stroke, and need for revascularization. 1

Mechanism and Evidence Base

Inflammation plays a key role in atherosclerosis pathophysiology, and colchicine acts as an anti-inflammatory agent that:

• Inhibits the NLRP3 inflammasome
• Concentrates in leukocytes and blocks tubulin polymerization
• Reduces production of pro-inflammatory cytokines (IL-1β and IL-18)

Key Clinical Trials

Two major randomized controlled trials provide the strongest evidence for colchicine in CAD:

1. COLCOT (Colchicine Cardiovascular Outcomes Trial):

   • Patients with recent MI (≤30 days) randomized to colchicine 0.5 mg daily vs. placebo
   • Primary endpoint reduced by 23% (HR 0.77; 95% CI, 0.61-0.96)
   • Significant reduction in stroke (HR 0.26; 95% CI, 0.10-0.70) 1
   • Absolute risk difference of 0.6% after mean follow-up of 23 months

2. LoDoCo2 (Low-Dose Colchicine 2):

   • Patients with stable CAD (≥6 months) randomized to colchicine 0.5 mg daily vs. placebo
   • Primary endpoint reduced by 31% (HR 0.69; 95% CI, 0.57-0.83)
   • Secondary endpoint of CV death, MI, or stroke reduced by 28% 1

Clinical Recommendation Algorithm

For whom to consider colchicine:

• Patients with established atherosclerotic CAD
• Both acute (post-MI) and chronic coronary syndromes
• Particularly beneficial in those with evidence of systemic inflammation

Dosing:

• 0.5 mg daily (standard dose used in major trials)

Monitoring:

• Assess for gastrointestinal side effects (diarrhea most common)
• Monitor for potential drug interactions, especially with CYP3A4 inhibitors

Efficacy Outcomes

Meta-analyses of RCTs show colchicine reduces:

• Major adverse cardiovascular events (MACE) by 31-35% 2, 3
• Myocardial infarction by 23-27% 2, 3
• Stroke by 52-53% 2, 3
• Need for coronary revascularization by 39% 2

Safety Considerations

• Generally well-tolerated at low doses

• Most common adverse effect is diarrhea

• Contraindicated in patients with:

  • Blood dyscrasias
  • Severe renal impairment (CrCl <15 mL/min)
  • Severe hepatic impairment
  • Concomitant use of P-glycoprotein and/or strong CYP3A4 inhibitors 1

• No significant increase in all-cause mortality in major trials

• Some studies suggest a potential small increase in non-cardiovascular mortality that requires further investigation 3

Guideline Recommendations

The 2024 ESC Guidelines for Chronic Coronary Syndromes give colchicine a Class IIa recommendation (Level of Evidence A), stating that "in CCS patients with atherosclerotic CAD, low-dose colchicine (0.5 mg daily) should be considered to reduce myocardial infarction, stroke, and need for revascularization." 1

For patients after acute coronary syndrome, the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline gives colchicine a Class IIb recommendation (Level of Evidence B-R), stating that "low-dose colchicine may be reasonable to reduce risk of MACE." 1

Clinical Implementation

Colchicine represents a valuable addition to standard therapy for CAD, offering a unique anti-inflammatory mechanism that complements traditional risk factor modification. Its low cost, established safety profile, and significant cardiovascular benefits make it an attractive option for secondary prevention in patients with established coronary artery disease.