Core Concepts
Colchicine, an anti-inflammatory drug, has shown promise in reducing the risk of major adverse cardiovascular events (MACE) in patients with established atherosclerotic disease or multiple cardiovascular risk factors.
Abstract
The article discusses the growing evidence supporting the use of colchicine in treating atherosclerotic cardiovascular disease (ASCVD). Key points:
Colchicine's mechanism of action: It dampens inflammatory markers on neutrophils, reducing their ability to adhere to inflamed or injured endothelium, which is a key contributor to plaque formation and rupture.
Clinical evidence:
The CANTOS trial showed that reducing high-sensitivity C-reactive protein (hsCRP) levels, a marker of inflammation, was associated with a lower risk of MI, stroke, or cardiovascular death.
The COPE-PCI Pilot trial demonstrated the benefit of targeting the interleukin pathways, which colchicine is known to affect.
Ongoing trials, such as POPCORN and CLEAR SYNERGY, are further investigating the role of colchicine in managing patients with acute coronary syndrome.
Preliminary data from a neutrophil biomarker substudy of CLEAR SYNERGY showed that colchicine reduced neutrophil adhesion to endothelial cells, neutrophil chemotaxis, and neutrophil activation, potentially inhibiting inflammasomes and decreasing IL-1β production.
Colchicine has been consistently shown to reduce the risk of recurrent myocardial infarction in patients with cardiovascular disease or at high risk, based on both retrospective and prospective studies.
Barriers to wider adoption: Confusion around the approved 0.5 mg dose for cardiovascular disease versus the 0.6 mg dose for gout, potential gastrointestinal side effects, and polypharmacy in these patients.
Stats
Patients who received canakinumab and achieved hsCRP < 2 mg/L had a statistically significant 25% lower risk of MI, stroke, or cardiovascular death than those who received placebo.
Quotes
"Colchicine dampens inflammatory markers on neutrophils so that they are less likely to be attracted to inflamed or injured endothelium, which would be the site of where plaque is building up or where the plaque has ruptured in the setting of a heart attack."
"There are multiple studies, both retrospective studies in gout cohorts as well as prospective studies in the cardiovascular cohort, that all show consistently one thing, which is that colchicine continues to reduce the risk of having a recurrent MI in patients who either have cardiovascular disease or are at high risk of having cardiovascular disease."