ESC 2023 Update: Colchicine does not reduce primary outcomes in patients undergoing major non-cardiac thoracic surgery: COP-AF trial

The study included 3,209 patients from 45 sites in 11 countries. The mean age was 68 years and 48.4% were women. Clinically important AF developed in 103 of 1,608 (6.4%) patients assigned to colchicine and 120 of 1,601 (7.5%) patients assigned to placebo, for a hazard ratio (HR) of 0.85 (95% confidence interval [CI] 0.65 to 1.10) and absolute risk reduction (ARR) of 1.1% (95% CI -0.7 to 2.8, p=0.22). MINS occurred in 295 (18.3%) patients assigned to colchicine and 325 (20.3%) patients assigned to placebo, HR 0.89 (95% CI 0.76 to 1.05) and ARR 2.0% (95% CI -0.8 to 4.7, p=0.16).

There were no significant differences between treatment groups in key secondary outcomes, including the composite of all-cause mortality, nonfatal MINS and nonfatal stroke, HR 0.88 (95% CI 0.75 to 1.03); the composite of all-cause mortality, nonfatal myocardial infarction (MI) and nonfatal stroke, HR 0.67 (95% CI 0.39 to 1.17); MINS not fulfilling the fourth universal definition of MI, HR 0.90 (95% CI 0.76 to 1.06); and MI, HR 0.86 (95% CI 0.41 to 1.81).

In post-hoc analyses, the composite outcome of clinically important perioperative AF or MINS occurred in 360 (22.4%) patients in the colchicine group and in 415 (25.9%) patients in the placebo group (HR 0.84; 95% CI 0.73 to 0.97). The composite outcome of vascular mortality, nonfatal MINS, nonfatal stroke or clinically important perioperative AF occurred in 364 (22.6%) patients in the colchicine group versus 422 (26.4%) in the placebo group (HR 0.83; 95% CI, 0.72 to 0.96). Six patients had a stroke, 1 (0.1%) in the colchicine group and 5 (0.3%) in the placebo group (p=0.12).

From a safety perspective, the composite outcome of sepsis or infection occurred in 103 (6.4%) patients in the colchicine group and 83 (5.2%) patients in the placebo group (HR 1.24; 95% CI 0.93 to 1.66). Colchicine increased the incidence of non-infectious diarrhoea, 134 (8.3%) versus 38 (2.4%) patients, HR 3.64 (95% CI 2.54 to 5.22). No treatment was required in 66 (38.4%) cases of diarrhoea, 15 (8.7%) patients needed intravenous hydration, 2 (1.2%) received antibiotics, and 1 (0.7%) patient required readmission for diarrhoea. In the colchicine group, the median (interquartile range) length of stay was 5 (4-7) days in patients with diarrhoea and 5 (3-7) days in those without diarrhoea.

Principal investigator Dr. David Conen of the Population Health Research Institute, Hamilton, Canada said: “Colchicine did not significantly reduce the incidence of the co-primary outcomes of clinically important perioperative AF or MINS. Colchicine increased the risk of non-infectious diarrhoea, but our data suggest that these episodes were temporary and benign. Despite these findings, several results provide an encouraging signal of benefit for colchicine to reduce the incidence of adverse cardiovascular outcomes in patients undergoing major non-cardiac thoracic surgery. Future trials should further investigate the role of colchicine in the prevention of these events in patients undergoing surgery.”