Colchicine is an anti-inflammatory treatment known for more than two centuries, inexpensive, used for decades in the treatment of gout, chronic diseases, but also in cardiology, in acute pericarditis. It intervenes on many cellular processes, including the function of inflammasoma, the release of cytokines and phagocytosis within the atherosclerosis plate.
At 0.5 mg per day, it has shown a significant reduction in the main judgment criterion in patients Stable coronary workers – in the Lodoco2 (1) – and After myocardial infarction – in the ColcoT study (2).
Colchicine is well indicated in post-infarction
This explains that learned companies recommend the use of colchicine in coronary workers, to its low dosage and respecting contraindications. Despite these evidence, it is little used, especially in France, where it suffers with a bad reputation, mainly concerning its digestive tolerance. The lack of dissemination by industrial networks probably does not help either.
The way of inflammation
The first demonstration that IGI on inflammation reduces cardiovascular events was made in 2017, with the Cantos study, on a human monoclonal antibody inhibiting IL-1B, canakinumab. It had reduced cardiovascular events after 15 %myocardial infarction.
An old effective medication but that no one has of interest to defend
Neutral results on the main criterion
But the lack of enthusiasm has changed into distrust with the Clear Synergy study which evaluated, in patients with acute myocardial infarction treated with angioplasty, on the one hand colchicine for its ability to reduce recurring atherosclerous events, and on the other hand Spironolactone with a composite criterion of heart failure (CI) and atheroscler events (3). We will not approach this second aspect here.
Regarding colchicine, the main composite criterion included: cardiovascular death, recurrence of myocardial, stroke or non -planned revascularization.
Between February 2018 and November 2022, the test recruited 7,062 participants from 104 centers in 14 countries (including around 2,500 in four sites in Macedonia). The average age of patients was 61 and 20 % were women.
The study is neutral on the main criterion: HR = 0.99; Ic95 % [0,85-1,16], p = 0.93 (see figure). Among the secondary results, we can emphasize the right tolerance, but also the reduction of non -cardiovascular deaths in the Colchicine group compared to placebo: HR = 0.68 IC95 % [0,46-0,99].
Redosage and re-sample
The colchicine dosage used in this test was initially based on weight, patients weighing 70 kg or more receiving the 0.5 mg dose twice a day for the first three months. So, as a reminder, the double of Colco and Lodoco2 studies.
After an intermediate analysis, showing higher than expected treatment stop rates, the dosage was revised for daily administration of colchicine throughout the treatment period, regardless of body weight.
Then, due to a rate of events lower than expected, the sample size has been increased by 4,000 to 7,000 patients, to maintain a study power of 80 %, and follow -up was extended for median monitoring estimated at 3.5 years.
A disruption by the pandemic
While the old (spironolactone) and recent (colchicine) data let the study have to be expected, the study accumulates disappointments. How to explain it? In addition to the questions raised previously, let us emphasize the 22 % reduction in the incidence of the main criterion events before the pandemic. This effect was lost during the pandemic, with an interaction between the COVID-19 phase and the effect of treatment (p < 0,10).
The reversed relationship between the incidence of IM non-fatal and deaths all causes in Clear Synergy is consistent with the well-known impact of COVID-19: first on the management of patients, then the sub-declaration of events in research. In some studies, major sub-declarations, close to 60 %, have been reported, which could largely explain the loss of efficiency noted during the pandemic.
(1) nidorfm’s sm it old. N English j med. 2020 Nov 5; 383 (19): 1838-47
(2) Tardif JC et al. N Engl J Med. 2019 Dec 26; 381 (26): 2497-505
(3) Jolly SS et al. N Engl j with. 2025 Feb 13; 392 (7): 633-42
