The results of the LoDoCo2 trial establish colchicine as a potential new option for long-term prevention of CV events in patients with chronic coronary disease

 Editor's note: Doctor Mark Nidorf  revealed the answer as he presented results from the LoDoCo2 trial as a Hot Line at ESC Congress 2020. International Circulation（China） then interviewed Dr. Mark Nidorf about the trial.

 

Dr. Mark Nidorf 

International Circulation：The lodoco2 study led by you was successfully selected into the hot line of this year's ESC conference to discuss the effect of low-dose colchicine on coronary heart disease. Would you like to introduce the main results of this study and its clinical significance?

Dr Nidorf: We looked at patients who had established coronary disease, and who had been clinically stable for at least six months. They didn’t have any advanced heart failure or renal disease. In the follow-up period, we found there was a significant reduction in the risk of heart attack, cardiovascular death, ischemic stroke and the need for coronary stenting or bypass. We also looked at the data in more detail, and even without revascularization, the results for the hard endpoints of death, heart attack and stroke were significant. Individually, the outcomes for myocardial infarction and the need for intervention with stents or bypass were also significantly reduced. These benefits occurred early, and over the five-year period, there was a 30% reduction in the risk for major outcomes. Furthermore, the treatment appeared safe.

International Circulation：The general public may have doubts about the safety of universal use of colchicine for secondary prevention. What is the safety outcome of LoDoCo2 trial? Are the results of this trial strictly limited to patients?

Dr Nidorf: Very importantly, the results confirm that the treatment was very well tolerated. There was an early run-in period, and we found that over 90% of people could tolerate colchicine without any difficulty. Of those who could tolerate the treatment, the long-term tolerance was excellent. That fits in with experience in the use colchicine in other conditions. There was no increased risk of cancer. There was no increased risk of infection or pneumonia, in particular (that signal was seen in COLCOT, but not in this study). So, the significance of the study is quite clear. The treatment was used in patients who were already receiving aspirin and moderate- or high-dose statins, so it can be used quite safely in this group of patients that we see in our clinics on a routine basis. Furthermore, the price of colchicine is likely to be low, because it is never going to be patented for this purpose due to the way the studies have been reported. The drug is widely available around the world. It will help individual patients, but there is a real chance that, if widely adopted, it can impact significantly on the global burden of heart disease. That is important.

International Circulation: What are the main mechanisms of cardiovascular benefits of colchicine? Is 0.5 mg per day a necessary dose definition? What further research needs to be done before it is formally used as a standard of clinical practice?

Dr Nidorf: That’s a good question. When we started this study, we used 0.5 mg because that was the only dose available to us. We probably don’t see any real reason to reduce that. Some people who are intolerant do tolerate a 0.25 mg dose well, and some of those can progress to the full dose, but not all. So maybe in those who show intolerance, you could try a smaller dose. We don’t think there is a lot to be gained by increasing up to 1 mg per day, because we are more worried about the potential for toxicity. We would much rather get the gains we can at the current dose that we have. The dose we use in Australia (and I suspect throughout Asia and Europe) is 0.5 mg. In America, they don’t make that dose, but use 0.6 mg. There will be some dosing studies done, but probably most of the world would use 0.5 mg per day.