Colchicine is an old drug with several anti-inflammatory properties that has traditionally been used to treat various rheumatic disorders (for example, gout and Behçet disease, among others).1 Specifically, it prevents the development of microtubules by inhibiting leukocyte function, and blocks the assembly of the NOD-like receptor P3 (NLRP3) inflammasome, preventing the release of IL-1β and the expression of other proinflammatory cytokines, some of which are known to play a role in cerebrovascular disease, such as MMP-9.2,3
Colchicine is used similarly to statins in the prevention of ischaemic stroke. Thus, in the Scandinavian Simvastatin Survival Study (4S), the first randomised prospective trial of a statin, simvastatin not only decreased overall mortality (30%) and the frequency of coronary events (34%), but also the frequency of stroke (30%).4
It should be noted that all patients in the 4S trial presented coronary artery disease (CAD). Furthermore, the majority of trials addressing the secondary prevention of CAD (4S, CARE, LIPID, GREACE, and TNT) found statins to be beneficial in stroke prevention. Finally, in the SPARCL trial, the first trial of secondary stroke prevention in patients without CAD, atorvastatin significantly reduced stroke.5
In this regard, colchicine has emerged as a therapeutic option for the secondary prevention of cardiovascular disease in patients with CAD.
Over the past 3 decades, several observational and randomised studies have assessed the impact of colchicine in patients with CAD and shown a reduction in the frequency of ischaemic events, including revascularisation, myocardial infarction, and also stroke or transient ischaemic attack (TIA).2,3
Similarly, patients surviving ischaemic stroke present greater risk of new events, approximately 30% at 5 years, partly due to arterial inflammation,6 also known as residual inflammatory risk.7
Thus, therapies specifically aiming to treat the inflammatory risk may decrease the rate of recurrent events. In the paradigmatic CANTOS trial, inhibition of the NOD-like receptor protein 3 inflammasome using the anti–IL-1β monoclonal antibody canakinumab decreased the rate of cardiovascular events in patients with elevated high-sensitivity C-reactive protein test results, also showing a possible 30% reduction in the risk of stroke.7
In fact, in a recent prospective multicentre cohort study of 10 499 patients with ischaemic stroke or TIA, residual inflammatory risk (defined as presenting an LDL cholesterol level < 100mg/dL and high-sensitivity C-reactive protein level ≥ 3mg/L) was associated with recurrent stroke (hazard ratio, 1.18; 95% CI, 1.00-1.40).8
A systematic review and meta-analysis of randomised controlled trials showed that the decrease in severe cardiovascular events with colchicine was greatest for stroke, with reductions in risk of 62%, 44%, and 38% for ischaemic stroke, emergency coronary revascularisation, and myocardial infarction, respectively.2
Another recent meta-analysis of randomised controlled clinical trials including 6630 patients at high cardiovascular risk specifically analysed the role of colchicine in stroke prevention. The use of colchicine led to a significant reduction in the risk of stroke (odds ratio, 0.33; 95% CI, 0.15-0.70).9
Colchicine would reduce not only the growth of the plaque,2,3 but also the risk of atrial fibrillation,10 and even prevent both the progression of the peripheral vascular disease at the carotid level11 and the progression of aortic aneurysms, by inhibiting the degradation of the extracellular matrix.12
Several clinical trials are currently assessing the usefulness of colchicine in the prevention of vascular events after a stroke or TIA. Thus, the CONVINCE trial, which includes 3154 patients with non-cardioembolic stroke or high-risk TIA, aims to determine whether adding colchicine to the standard treatment leads to a reduction in the recurrence of stroke and vascular events.13
In the meantime, the 2021 guidelines of the European Society of Cardiology recommend for the first time the use of anti-inflammatory treatment for the secondary prevention of atherosclerosis. They recommend considering low-dosed colchicine (0.5mg once daily) for the secondary prevention of cardiovascular disease when other risk factors are not sufficiently controlled, or if recurrent events occur despite optimal treatment (grade of recommendation IIb, level of evidence I).14
Therefore, colchicine, a safe and frequently used anti-inflammatory drug that inhibits the inflammation associated with vascular disease, creates a new paradigm in the prevention of atherosclerotic ischaemic stroke. We may soon see a new change in our clinical practice.
