Colchicine

 The earliest medical use of colchicine possibly dates to 1500 BCE based on writings that describe the use of a plant likely containing colchicine for the treatment of pain and swelling (Figure 1). In the 550s CE, Alexander of Tralles, a physician in the Byzantine Empire, described the use of hermodactyl, a plant resembling the Autumn crocus, for the treatment of gout as well as the botanical’s adverse gastrointestinal effects. Baron Anton Stork provided an early description of the use of colchicine for pericarditis in the 18th century. Around the same time, Nicolas Husson developed the first commercial colchicine preparation. [1]

Colchicine is an anti-inflammatory alkaloid. [1]

0.6 mg. BID

Colchicine has multiple interactions with other drugs. It is a substrate for CYP3A4 and P-glycoprotein (P-gp), and concomitant administration with CYP3A4/P-gp inhibitors can cause life-threatening drug–drug interactions (DDIs) such as pancytopenia, multiorgan failure, and cardiac arrhythmias. [3]

Colchicine was study to reduce inflammation thus reduce atherosclerotic heart disease. 

Colchicine has assumed an important role in the management of cardiovascular

inflammation ≈3500 years after its first medicinal use in ancient Egypt. Primarily used in high doses for the treatment

of acute gout flares during the 20th century, research in the early 21st century demonstrated that low-dose colchicine

effectively treats acute gout attacks, lowers the risk of recurrent pericarditis, and can add to secondary prevention of

major adverse cardiovascular events. As the first Food and Drug Administration–approved targeted anti-inflammatory

cardiovascular therapy, colchicine currently has a unique role in the management of atherosclerotic cardiovascular disease.

The safe use of colchicine requires careful monitoring for drug-drug interactions, changes in kidney and liver function, and

counseling regarding gastrointestinal upset. Future research should elucidate the mechanisms of anti-inflammatory effects

of colchicine relevant to atherosclerosis, the potential role of colchicine in primary prevention, in other cardiometabolic

conditions, colchicine’s safety in cardiovascular patients, and opportunities for individualizing colchicine therapy using clinical

and molecular diagnostics. [1]

Randomized clinical trials established low-dose colchicine as an effective treatment for pericarditis and atherosclerotic cardiovascular disease. [1]

• The mechanisms through which colchicine exerts its beneficial anti-inflammatory and cardiovascular effects remain an area of vigorous investigation.
• When prescribing colchicine, clinicians must consider drug-drug interactions, impaired kidney and liver function, and adverse effect monitoring.
• While the use of colchicine in cardiovascular disease requires much further study, landmark trials have pointed the way for its clinical adoption as an approved targeted anti-inflammatory agent in the management of atherosclerotic risk.

In an open-label, randomized clinical trial of colchicine versus no colchicine (LoDoCo [Low-Dose Colchicine]), colchicine lowered the risk of the composite of acute coronary syndrome (ACS), out-of-hospital cardiac arrest, or noncardioembolic ischemic stroke by 67% in people with stable coronary artery disease. [1]

More definitive evidence of the benefits of colchicine on atherosclerotic cardiovascular disease events comes from the LoDoCo2 trial and COLCOT (Colchicine Cardiovascular Outcomes Trial; Table). LoDoCo2 and COLCOT each compared the effects of adding either low-dose colchicine (0.5 mg QD) or placebo to background guideline-directed medical therapy, including antiplatelet and statin therapy, on major adverse cardiovascular events in ≈5000 participants per trial over 2 years of follow-up. COLCOT enrolled individuals within 30 days of a myocardial infarction while LoDoCo2 enrolled individuals with chronic coronary artery disease (at least 6 months following an ACS). In both studies, low-dose colchicine lowered the risk of major adverse cardiovascular events by >30% compared with placebo. [1]

A total of 5522 patients underwent randomization; 2762 were assigned to the colchicine group and 2760 to the placebo group. The median duration of follow-up was 28.6 months. A primary end-point event occurred in 187 patients (6.8%) in the colchicine group and in 264 patients (9.6%) in the placebo group (incidence, 2.5 vs. 3.6 events per 100 person-years; hazard ratio, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P<0.001). A key secondary end-point event occurred in 115 patients(4.2%) in the colchicine group and in 157 patients (5.7%) in the placebo group (incidence, 1.5 vs. 2.1 events per 100 person-years; hazard ratio, 0.72; 95%

CI, 0.57 to 0.92; P = 0.007). The incidence rates of spontaneous myocardial infarction or ischemia-driven coronary revascularization (composite end point), cardiovascular death or spontaneous myocardial infarction (composite end point), ischemia driven coronary revascularization, and spontaneous myocardial infarction were

also significantly lower with colchicine than with placebo. The incidence of death

from noncardiovascular causes was higher in the colchicine group than in the

placebo group (incidence, 0.7 vs. 0.5 events per 100 person-years; hazard ratio,

1.51; 95% CI, 0.99 to 2.31). [2]

CONCLUSIONS

In a randomized trial involving patients with chronic coronary disease, the risk of

cardiovascular events was significantly lower among those who received 0.5 mg of

colchicine once daily than among those who received placebo. (Funded by the

National Health Medical Research Council of Australia and others; LoDoCo2 Australian

New Zealand Clinical Trials Registry number, ACTRN12614000093684.) [2]

[1]L Buckley. Colchicine’s Role in Cardiovascular Disease Management. Arteriosclerosis, Thrombosis, and Vascular Biology.  44:5 May 2024.

[2] S Nidorf et al. Colchicine in Patients with Chronic Coronary Disease. NEJM. Aug 31, 2020. 

[3] Hansten PD et al. Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management. Drug Saf. 2023 Mar;46(3):223-242.