You can teach an old drug new tricks

For many years, doctors have been using the very old and inexpensive drug, colchicine, to treat acute episodes of gout. Gout is an extremely painful arthritic condition which typically affects the big toe, related to excessive levels of uric acid in the blood stream. Many people in the general public wrongly see gout as a rich man’s disease related to the excessive ingestion of good red wine and pate.

Gout, however, is a metabolic disorder closely related to insulin resistance. Insulin resistance is the most common metabolic genetic abnormality in the world, affecting 30% of Caucasians, 50% of Asians and close to 100% of people with darker or olive skin. The clinical manifestation of insulin resistance is tendency to diabetes, hypertension, cholesterol abnormalities characterised by a high triglyceride level and low HDL and abdominal obesity (males-greater than 95 cm around the waist and females-greater than 80 cm. I am sorry ladies, I do not make the rules).

Image source: Photo by Artem Maltsev, Unsplash

All of these features lead to what is known as metabolic syndrome which has very clear and definite links to all forms of cardiovascular disease such as heart disease or stroke, fatty liver, gout and many common forms of cancer such as breast, prostate and colon cancer. If a person is unfortunate enough to suffer gout because of these elevated uric acid levels, excessive consumption of alcohol or rich foods may precipitate an episode. Colchicine given at the onset of the episode can relieve the pain rather rapidly but also may cause diarrhoea.

A few years back, a colleague of mine in Perth, Dr Mark Nidoff performed a landmark study known as the LODOCO trial where he gave low-dose colchicine (one tablet-500 µg daily) in a placebo controlled trial to a group of people who had already suffered an acute coronary event. There was a reduced rate for further coronary events by 67% in the people given colchicine.

As this was a relatively small single centre study, this was recently replicated in Canada in a trial known as COLCOT involving 4745 patients who were just over 2 weeks following a heart attack and followed for just under 2 years. All of these patients were on high-intensity statin drugs to lower their cholesterol. The major end point of the study was reduction in cardiovascular death, heart attack, stroke, angina leading to an intervention such as stenting or coronary artery bypass grafting along with a resuscitated cardiac arrest. The overall reduction in these events was 27% and statistically significant. Interestingly, the biggest reductions were a 74% reduction in stroke and a 50% reduction in the need for bypass surgery or stenting. There was a minimal increase in diarrhoea in the patients treated with colchicine but interestingly 21 cases of pneumonia in the colchicine treated patients whereas there were only 9 cases in the patients on placebo, still very small numbers.

There are 3 other trials being conducted at present in people with varying types of vascular disease but I must say that I have been using colchicine on a regular basis since the initial LODOCO trial results showed such a strong benefit with minimal downside.

You may ask the highly relevant question-why does this work? The answer to this is that colchicine is a very effective anti-inflammatory that works on the pathways involved in the generation of fatty plaques in the wall of the arteries. A trial using a very expensive monoclonal antibody showed a significant reduction in vascular events in patients with heart disease but interestingly, not as striking results as seen using colchicine, a very inexpensive drug that has been around for years and is well off patent.

It is an interesting allegory of life that what seems new, young and exciting is not always as beneficial as what has been around for a long time with vast experience and a strong safety profile. I am sure you have no doubt as to what I am inferring. So, clearly, you can teach an old drug new tricks and in this case the tricks are extremely valuable.