Colchicine Indicated for the Prevention of Atherosclerotic Cardiovascular Events

Derived from Nature, Old Drug Wins Broad Regulatory Indication, 31% Risk Reduction In LoDoCo2 Trial

By Peter A. McCullough, MD, MPH

It rare that enough research is done on an old drug to win a new regulatory indication. In 2023, oral colchicine was FDA approved for the prevention of atherosclerotic cardiovascular events (myocardial infarction, stroke, coronary revascularization, and cardiovascular death).

Here is some more information on this medication from the Cochrane Collaboration:

“Colchicine is an ancient drug with strong anti‐inflammatory effects (Niel 2006). For centuries, acute gout was treated with extracts from autumn crocus (Colchicum autumnale) (Cocco 2010; Slobodnick 2015), until the active pharmaceutical ingredient (the lipophilic alkaloid, colchicine) was identified in the 18th century (Slobodnick 2015; Slobodnick 2018). Colchicine blocks cell division, specifically mitosis, by binding to tubulin and preventing the elongation of microtubules. At lower concentrations it leads to microtubule arrest, and at higher concentrations it leads to microtubule depolymerization (Dalbeth 2014). Although the exact mechanisms by which colchicine acts on the immune system are not fully understood, it appears to exert anti‐inflammatory effects through multiple modes of action, which, together, result in altered leukocyte adhesion and migration, as well as cytokine production and secretion (Leung 2015; Slobodnick 2018). In addition to gout, colchicine is used to treat numerous systemic inflammatory diseases, including familial Mediterranean fever, Behçet's disease, primary biliary cirrhosis, and pericarditis (Cocco 2010; Imazio 2020; Slobodnick 2018). In clinical practice it is important to note that the therapeutic window of colchicine is relatively narrow and inter‐individual pharmacokinetic variability is high (D’Amario 2021; Leung 2015; Niel 2006).”

Colchicine, first FDA approved for gout in 1961 was later studied in various trials, including the COLCOT, LoDoCo, and LoDoCo2 trials, which evaluated the anti-inflammatory effects of colchicine on reducing cardiovascular events in patients with established ASCVD or patients at risk of developing ASCVD. Atherosclerosis is a common problem with buildup of cholesterol inciting inflammation and secondary proliferation of matrix proteins that narrow arteries. Most current therapies to reduce ASCVD are based on mechanisms to lower cholesterol. However, inflammation also has a critical role in ASCVD that is independent of cholesterol levels. The inflamed endothelium in the arteries attracts the migration, adhesion, and activation of leukocytes, the majority being neutrophils. C-reactive protein is an inflammatory biomarker associated with an increased risk of cardiovascular (CV) events. Colchicine handles this component of atherosclerosis.