46 CLINICAL FOCUS
46 CLINICAL FOCUS
11 APRIL 2025 ausdoc. com. au
Therapy Update
Colchicine in coronary artery disease
Cardiology
Dr John Lee Cardiology advanced trainee, Peninsula Health, Frankston, Victoria. Hui Zhen Lo Medical student, Monash University, Melbourne, Victoria.
Professor Jamie Layland General and interventional cardiologist and director of cardiovascular research at Peninsula Health, Frankston; adjunct professor of medicine, Peninsula Clinical School, Monash University, Melbourne.
Professor Christian Hamilton-Craig Consultant cardiologist and director of cardiology at Noosa Hospital, Sunshine Coast; professor of medicine, University of Queensland and Griffith University, Brisbane.
Cheap, effective, widely available and easy to use— colchicine is an ideal adjunctive pharmacotherapy for some patients with coronary artery disease.
DESPITE advances in medicine, cardiovascular disease remains a leading cause of morbidity and mortality within Australia. 1 Patients with known coronary artery disease( CAD) have a high residual risk of subsequent major adverse cardiovascular events( MACE) compared to the general population, even when they have reached contemporary lipid-lowering targets and are adherent to antithrombotic therapy.
The inflammatory axis is pivotal in the development of atherosclerosis and plaque rupture. Large prospective trials have demonstrated that colchicine provides further cardioprotection in patients established on standard guideline-directed antithrombotic therapy and lipid-lowering therapy. In this context, colchicine presents as an ideal therapeutic option for achieving further cardioprotection. 2 Colchicine has not yet been TGA-approved or PBS-listed for the indication of CAD. But even when prescribed off-label, it is cheap and widely available, and is a safe and effective option to consider for secondary prevention.
This review aims to outline the rationale, evidence base and current guidelines for the use of colchicine in CAD and its role as an ideal adjunctive medication class to further improve patient outcomes.
Rationale for use in CAD
The inflammatory axis plays a key role in the development of atherosclerosis. While high lipid levels and hypertension promote cholesterol deposition in the vascular intima, it is the innate and adaptive immune systems that stimulate immune cell migration, foam cell accumulation, ensuant plaque growth and rupture, ultimately leading to cardiac events. 3
This‘ grumbling’ low-level inflammation, detected by high-sensitivity C-reactive protein( hsCRP), has proven to be a powerful predictor of recurrent cardiovascular events, consistently outperforming the predictive capacity of low-density lipoprotein( LDL) levels. 4
Mechanism of action
Normal coronary endothelium is resistant to adhesion and infiltration by circulating leukocytes. 5 In contrast, the inflamed endothelium that overlies atheroma attracts leukocyte populations, enabling adhesion, migration and extracellular release of granular enzymes that cause tissue injury and further propagate the innate immune response. 6
Colchicine has multiple effects on this atherobiology( see figure 1). One arm of its action is inhibiting polymerisation of tubulin heterodimers, thereby inhibiting microtubule formation. This has downstream effects of disrupting the cellular cytoskeleton, impairing intracellular protein transport and mitosis. 6 This suppresses the orchestration of myofibroblasts, smooth muscle cells and fibrosis that contribute to atherosclerotic plaque formation.
More impressively, however, colchicine inhibits the assembly and activation of the NLR family pyrin domain-containing 3( NLRP3) inflammasome. 5
Atherosclerotic lesions contain macroscopic deposits of cholesterol crystals, particularly in the necrotic core. These cholesterol crystals are potent stimulants of the NLRP3 inflammasome, resulting in the increased production of cytokines interleukin-1β, interleukin-6 and interleukin-18. This intracellular effect of colchicine is most pronounced in neutrophils and monocytes. This is helpful, as these white cell subtypes make up a large contingent of the leukocyte population within atherosclerotic plaque. Inhibiting the NLRP3 inflammasome’ s production of key cytokines helps stifle the mobilisation and activation of the innate immune system within the atherosclerotic plaque. This leads to plaque stability, prevention of plaque rupture and reduced rates of acute coronary syndromes( ACS). 2
Evidence base and clinical use
The first trial that demonstrated the benefits of colchicine in secondary prevention of coronary disease was the pilot LoDoCo trial. 7 This study recruited patients with stable coronary disease to low-dose colchicine of 500 µ g daily alongside standard therapy
NEED TO KNOW
There is a strong underlying immune basis for the development of atherosclerosis, which ultimately leads to cardiac events such as acute MI.
Colchicine is a sophisticated anti-inflammatory agent that is widely available, safe, well tolerated and protects against recurrent cardiac events for patients established on antithrombotic and lipid-lowering therapy.
Colchicine’ s role for secondary prevention of coronary artery disease has been ratified by international guidelines. Its use will continue to expand, likely into the stroke and peripheral vascular disease literature.
Colchicine has not yet been TGAapproved or PBS-listed for coronary artery disease. But it is cheap and widely available, even when prescribed off-label, so should be considered for suitable patients.
( with dual antiplatelet and statins), or to standard therapy alone. At a median three years’ follow-up, the colchicine arm had a significantly lower composite outcome of ACS, out-of-hospital cardiac arrest and ischaemic stroke( 5.3 % vs 16 %; p < 0.001). Following on from the success of the LoDoCo trial, the LoDoCo2 trial recruited 5522 patients with stable coronary disease who were randomised to placebo or colchicine 500 µ g daily and followed up for 28 months. 8 Patients randomised to colchicine had a 31 % lower composite risk of cardiovascular death, spontaneous MI, ischaemic
Figure 1. Colchicine’ s mechanism of action.