Colchicine: Ancient Anti-Inflammatory Could Prevent Atherosclerosis Like Aspirin (But at What Price?)

As long as 3,500 years ago, the plant source of the drug we now know as colchicine was already being described as a source of relief for swelling and rheumatism: In 1550 B.C., an Egyptian of great learning first wrote about the anti-inflammatory properties of the autumn crocus–colchicum autumnale–in a papyrus. One of the oldest known compendiums of herbal medical knowledge, it described preparations made from the colchicum plant. By the 1st century of the common era, gout and “dropsy” (edema) were added to the list of ailments colchicum were being used to relieve.

Benjamin Franklin, who suffered from dropsy himself, gets the historical credit for importing autumn crocus plants to the shores of North America from France, in fact. (Seriously, is there anything Franklin didn’t manage to invent, improve, or refine?)

Then in 2006, under the U.S. FDA’s “Unapproved Drug Program,” a small pharmaceutical company based in Pennsylvania managed to acquire the patent rights to single-ingredient colchicine (until 2029). And with those patent rights and revenues came a flurry of funding for new investigations into the drug’s properties and uses.

(Also, the price skyrocketed.)

The COLCOT Study Raises New Hopes–and More Research Questions

One of the new studies is raising a lot of eyebrows–and hopes about potential new applications for the drug.

While colchicine’s on-label uses have been restricted to gout, Behcet’s disease and Mediterranean fever, the latest news about potential benefits are emerging from a significant randomized, controlled, longitudinal, multicenter study of myocardial infarction patients: The COLCOT study. Professor Jean-Claude Tardif, research director of the Montreal Heart Institute, summed up the results in a late 2019 interview with Medscape:

“The COLCOT study included 4745 patients who were recruited within 30 days of their MI. They all received two antiplatelet agents and a statin, and they underwent angioplasty if necessary. Then they were assigned colchicine at a low dose of 0.5 mg/day or placebo. The average follow-up was 23 months, and we found a 23% reduction in the primary efficacy outcome, which was the combination of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring revascularization.”

The outcomes are encouraging and even in some cases surprising, especially with regard to stroke: Full study details are available in easily digestible bullet form at Wiki Journal Club.

Cautions and Contraindications

At the same time, as medical advocates and health care professionals, it’s important to remain vigilant in these early days, before additional studies. We need to remain alert to potential drawbacks, unforeseen consequences, and especially risks due to medication interactions.

And while the early headline “Colchicine Could Become the Next Aspirin” is a sexy one, in reality, colchicine’s safety profile is quite different than aspirin’s. It must not, for example, be administered to patients with renal (kidney) or hepatic (liver) impairment in combination with drugs that inhibit both P-glycoprotein and CYP3A4 (clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit, among others). The package warning itself states “Such combinations have resulted in life-threatening or fatal colchicine toxicity.” (OTC aspirin bottles, I will note here, carry no such stark warnings).

Once more for emphasis: Prescribing physicians and patients should be aware that colchicine should not be taken under certain circumstances:

-Known existing kidney or liver damage

-Short-term or long-term consumption of other medications or foods that inhibit the same metabolic pathways as colchicine

Based on the initial findings of the COLCOT study, the same researchers are now following up with a second study of low-dose colchicine for atherosclerotic conditions–the LoDoCo (low dose colchicine) study, currently following more than 5,500 MI patients.

We’ll keep an eye on new findings about Ben Franklin’s favorite crocus, one of humanity’s oldest biochemical interventions for inflammatory damage, even as we continue to keep an eye on the price of the name-brand and generic tablets and advocate for safe, responsible prescribing.

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