FDA approves gout medication to treat heart disease

Colchicine, a widely available gout medication, has been approved by the US FDA to be used in low doses to prevent cardiovascular events in patients with proven coronary disease. The approval follows a discovery by Dr Mark Nidorf and Professor Peter Thompson from the Harry Perkins Institute of Medical Research, whose initial findings were published in the American Journal of Cardiology in 2007 and were followed by the LoDoCo (Low Dose Colchicine) trial.

The initial LoDoCo clinical trial was conducted with 500 patients in Western Australia between 2008 and 2012. Results from that trial showed that it had the potential to significantly reduce the risk of major cardiovascular events in patients with chronic heart disease. Further testing in a larger trial was therefore warranted.

“The dramatic results of our initial LoDoCo trial sparked global interest in this potentially game-changing treatment,” Nidorf said. “We therefore designed and conducted a second large multicentre clinical trial in over 5000 patients. This trial was called LoDoCo2 and was an international collaboration between West Australian researchers and colleagues in The Netherlands. The commitment of the patients throughout the five-year trial was impressive, and there was a low rate of withdrawal from the trial.”

The results of the LoDoCo2 trial, published in the New England Journal of Medicine in 2020, showed that there was a 31% reduction of major adverse cardiovascular events in patients on optimal medical therapy with cholesterol-lowering drugs. The results also indicated that a low dose of 0.5 mg of colchicine per day was well tolerated and appeared safe, without any increase in the incidence of cancer or interaction with other commonly used medications including statin therapy.

“While colchicine has many actions, the most likely explanation for its effect is to dampen the inflammatory reaction which occurs when cholesterol changes from a relatively benign semi-liquid form to a highly irritant crystalline form within the atherosclerotic plaque,” Nidorf explained. “This is similar to the anti-inflammatory benefit the drug has in gout when uric acid changes to a crystalline form inside a joint, causing painful gouty arthritis.”

Since LoDoCo2 was reported, over 11,000 patients in other clinical trials conducted in Australia and Canada have confirmed the benefits and safety of adding low-dose colchicine to usual medical therapy in patients with coronary disease. In the next few years, two other trials that collectively include over 10,000 patients will report the effect of colchicine in patients who have had a recent stroke or heart attack.

Low-dose colchicine is now registered for secondary prevention in patients with heart disease in the US, Canada and South America and included in guideline therapy in Europe. Given the FDA decision, it is hoped that the TGA will also approve colchicine for this purpose in Australia in the near future.

“FDA approval is a strong affirmation by the most influential regulatory authority in the world that the results of our LoDoCo trials are valid and that low-dose colchicine is both effective and safe to use in patients with coronary disease,” Thompson said.

“Importantly, colchicine is inexpensive and readily available as it has been repurposed for this indication.”

Image caption: Dr Mark Nidorf and Professor Peter Thompson.